ISAPP collaborates with NEC Society to help parents understand the role of probiotics in reducing the risk of necrotizing enterocolitis

/in Consumer Blog, News /by KC

By Dr. Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

To date, over 50 clinical trials on probiotics and necrotizing enterocolitis have been published. Medical organizations have considered the trials completed to date and have provided guidance (ESPHGAN) and recommendations (American Gastroenterological Association) for implementing probiotics in clinical practice.

As important as the science on this issue are the perspectives from parents of babies who have suffered from NEC or are at risk of developing the disease. Such parents consistently point to the need for credible and balanced educational materials about this condition. Recently, ISAPP has been fortunate to work with the NEC Society to develop materials that will help inform parents.

See the new ISAPP infographic Probiotics and Necrotizing Enterocolitis: What Parents Should Know.

Disponible también en español. Информация также доступна на русском языке.

Also, a recent ISAPP blog Probiotics to Prevent Necrotizing Enterocolitis: Moving to Evidence-Based Use by Dr. Ravi Patel MD, a neonatologist on the NEC Society’s Scientific Advisory Council, summarizes the state of the science supporting this use, including both controlled efficacy trials and post-implementation surveys.

The NEC Society is a nonprofit organization – the only US group dedicated to NEC – with the stated mission of “building a world without necrotizing enterocolitis (NEC) through research, advocacy, and education.” They advocate for families affected by NEC by bringing together critical stakeholders to improve understanding, prevention, and treatment for NEC. Jennifer Canvasser founded the NEC Society in 2014 after her son, Micah, died from complications of NEC just before his first birthday. Micah was born at 27-week’s gestation, placing him at increased risk of NEC. Despite Micah’s risk factors and his parents asking the care team to consider offering Micah probiotics, he was not treated with probiotics. Although it is impossible to know if probiotics could have changed Micah’s course, his parents feel that more could have been done to better protect Micah from the devastation of NEC. Micah’s photo is featured in the new infographic co-created by ISAPP and the NEC Society.

“It is vital for healthcare providers to support NICU parents in understanding the protective and risk factors associated with NEC,” Canvasser shared. “Parents are the most important members of their baby’s care team. For parents to effectively engage and contribute, they need to be supported in accessing and understanding important information related to their child’s health. This new resource on probiotics and NEC will help to ensure that NICU parents are informed and feel encouraged to ask questions so they can best advocate for their child.”

The NEC Society intends to use the new infographic as a resource available to NICU parents and providers. It will be downloadable from the websites of both the NEC Society and ISAPP, and it will be shared via both social media platforms. Once in-person events are possible again, print versions will be made available. ISAPP will also work with the NEC Society’s Scientific Advisory Council to explore how we can further disseminate this resource to NICUs.

Read more about the efforts of the NEC Society here:

Head of the Herd: Jennifer Canvasser, Founder and Director, Necrotizing Enterocolitis (NEC) Society

Family Reflections: harnessing the power of families to improve NEC outcomes

10 Things All Parents of NICU Babies Need to Know

9 Things You Need to Know About Necrotizing Enterocolitis

New ISAPP-led paper calls for investigation of evidence for links between live dietary microbes and health

/in ISAPP Science Blog, Consumer Blog /by KC

The past two decades have brought a massive increase in knowledge about the human gut microbiota and its links to human health through diet. And although many people perceive that regular consumption of safe, live microbes will benefit their health, the scientific evidence to date has not been sufficiently developed to justify adding a daily recommended intake of live microbes to food guides for different populations.

Recently, a group of seven scientists, including six ISAPP board members, published their perspective about the value of establishing the link between live dietary microbes and health. They conclude that although the scientific community has a long way to go to build the evidence base, efforts to do this are worthwhile.

The collaboration on this review was rooted in an ISAPP expert discussion group held at the 2019 annual meeting in Antwerp, Belgium. During the discussion, various experts presented evidence from their fields—addressing the potential health benefits of live microbes in general, rather than the narrow group of microbial strains that qualify as probiotics.

Below, the authors of this new review answer questions about their efforts to quantify the relationship between greater consumption of live microbes and human health.

Why is it interesting to look at the potential importance of live microbes in nutrition?

Prof. Joanne Slavin, PhD, RD, University of Minnesota

Current recommendations for fiber intake are based on protection against cardiovascular disease—so can we do something similar for live microbes? We know that intake of live microbes is thought to be health promoting, but actual recommended intakes for live microbes are missing.  Bringing together a talented group of microbiologists, epidemiologists, nutritionists, and food policy experts moves this agenda forward.

Humans need proper nutrition to survive, and a lack of certain nutrients creates a ‘deficiency state’. Is this the case for live microbes?

Dr. Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

I don’t think we’ll find that live microbes are essential in the same way that vitamins and minerals lead to deficiency diseases. After all, gnotobiotic animal colonies are viable. But I believe there is enough evidence to suggest that consumption of live microbes will promote health. Exactly how and to what extent remains to be established.

Why think about intake of ‘live microbes’ in general, rather than intake of probiotic & fermented foods specifically?

Prof. Maria Marco, PhD, University of California Davis

We are constantly exposed to microorganisms in our foods and beverages, in the air, and on the things we touch. While much of our attention has been on the microbes that can cause harm, most of our microbial exposures may not affect us at all or, quite the opposite, be beneficial for maintaining and improving health. Research on probiotic intake as a whole supports this possibility. However, probiotic-containing foods and dietary supplements are only a part of our dietary connection with live microbes. Non-pasteurized fermented foods (such as kimchi and yogurts) can contain large numbers of non-harmful bacteria (>10^7 cells/g). Fruits and vegetables are also sources of living microbes when eaten raw.  Although those raw foods they may contain lower numbers of microbes, they may be more frequently eaten and consumed in larger quantities. Therefore, our proposal is that we take a holistic view of our diets when weighing the potential significance of live microbe intake on health and well-being.

What are dietary sources of live microbes? And do we get microbes in foods besides fermented & probiotic foods?

Prof. Bob Hutkins, PhD, University of Nebraska Lincoln

For tens of thousands of years, humans consumed large amounts of microbes nearly every time they ate food or drank liquids. Milk, for example, would have been unheated and held at ambient temperature with minimal sanitation and exposed to all sorts of microbial environments.  Thus, a cup of this milk could easily have contained millions of bacteria. Other foods like fruits and vegetables that were also exposed to natural conditions could have also contained similar levels of microbes. Even water would have contributed high numbers of live microbes.

Thanks to advances in food processing, hygiene, and sanitation, the contemporary western diet generally contains low levels of microbes. Consider how many foods we eat that are canned, pasteurized, or cooked – those foods will contain few, in any live microbes. Fresh produce can serve as a source of live microbes, but washing, and certainly cooking, will reduce those levels.

For sure, the most reliable sources of dietary microbes are fermented foods and beverages. Even if a fresh lettuce salad were to contribute a million bacteria, a single teaspoon of yogurt could contain 100 times more live bacteria. Other popular fermented foods like kefir, kimchi, kombucha, and miso, can contain a large and relatively diverse assortment of live microbes. Other fermented foods, such as cheese and sausage, are also potential sources, but the levels will depend on manufacturing and aging conditions. Many fermented, as well as non-fermented foods are also supplemented with probiotics, often at very high levels.

What’s the evidence that a greater intake of live microbes may lead to health benefits?

Prof. Dan Merenstein, MD, Georgetown University

Studies have shown that fermented foods are linked to a reduced risk of cardiovascular disease, reduced risk of weight gain, reduced risk of type 2 diabetes, healthier metabolic profiles (blood lipids, blood glucose, blood pressure and insulin resistance), and altered immune responses. This link is generally from associative studies on certain fermented foods. Many randomized controlled trials on specific live microbes (probiotics and probiotic fermented foods) showing health benefits have been conducted, but randomized controlled trials on traditional fermented foods (such as kimchi, sauerkraut, kombucha) are rare. Further, no studies have aimed to assess the specific contribution of safe, live microbes in diets as a whole on health outcomes.

Why is it difficult to interpret past data on people’s intake of live microbes and their health?

Prof. Colin Hill, PhD, University College Cork

It would be wonderful if there were a simple equation linking the past intake of microbes in the diet and the health status of an individual (# MICROBES x FOOD TYPE = HEALTH). In reality, this is a very complex challenge. Microbes are the most diverse biological entities on earth, our consumption of microbes has not been deliberately recorded and can only be estimated, and even the concept of health has defied precise definitions for centuries. To further confuse the situation microbes meet the host in the gastrointestinal tract, the site of our enormously complex mucosal immune system and equally complex microbiome.  But the complexity of the problem should not prevent us from looking for prima facie evidence as to whether or not such a relationship is likely to exist.

Databases of dietary information have data on people’s intake of live microbes, but what are the limitations of our available datasets?

Prof. Dan Tancredi, PhD, University of California Davis

Surveys often rely on food frequency questionnaires or diaries to determine consumption of specific foods. These are notoriously prone to recall error and/or other types of measurement error. So, even just measuring consumption of foods is difficult. For researchers seeking to quantify survey respondents’ consumption of live microbes, these challenges become further aggravated because the respondents would not typically know the microbial content in the foods they consumed. Instead, we would have to have them tell us the types and amounts of the foods they ate, and then we would need to translate that into approximate microbial counts—but even within a particular food, the microbial content can vary, depending on how it was processed, stored, and/or prepared prior to consumption.

See ISAPP’s press release on this paper here.

Locally produced probiotic yogurt for better nutrition and health in Uganda

/in Consumer Blog, News /by KC

By Prof. Seppo Salminen, Director of Functional Foods Forum, University of Turku, Turku, Finland

Can locally produced probiotic yogurt be a way to increase the health and wealth of people in resource-poor areas of Uganda? Recently Dr. Nieke Westerik, a researcher from the Netherlands, partnered with a local Ugandan team to explore a yogurt production and distribution program similar to one that had previously proved successful in low-income areas of Argentina.

Since 2008, “Yogurito Social Program” has been operating in Argentina and now some 350,000 schoolchildren in less developed provinces enjoy the benefits of daily probiotic yogurt developed locally. Dr. Westerik (Free University of Amsterdam and Yoba 4 Life Foundation), with support from former ISAPP board member Prof. Gregor Reid, has now helped adapt the program to local needs in Uganda, making use of a well-known probiotic (Lacticaseibacillus rhamnosus GG) plus a yogurt starter (produced by the Yoba 4 Life Foundation) for production of the yogurt. The probiotic’s health effects have been demonstrated in human intervention studies.

The team worked on technical training and quality control of the locally produced yogurt, developing a production protocol suitable for Ugandan small-scale manufacture of probiotic fermented foods. Dr. Westerik’s team then conducted two clinical studies that demonstrated that the consumption of this probiotic product improved natural defenses and prevented respiratory infections (e.g. the common cold) and intestinal infections, which are the infectious conditions of greatest relevance in childhood in Uganda.

Yogurt is a new tool for individuals in developing areas of Uganda to achieve better health through diet, with potentially significant social and economic implications. Both the Ugandan and Argentinian experiences illustrate the power of microbes to positively impact the lives of women, men, and children. Given the positive results from these two different contexts, such activities could be replicated in other geographical areas—with either dairy, vegetable, or grain fermentations used locally with defined, well-studied starter cultures.

Further reading:

Julio Villena, Susana Salva, Martha Núñez, Josefina Corzo, René Tolaba, Julio Faedda, Graciela Font and Susana Alvarez. Probiotics for Everyone! The Novel Immunobiotic Lactobacillus rhamnosus CRL1505 and the Beginning of Social Probiotic Programs in Argentina. International Journal of Biotechnology for Wellness Industries, 2012, 1, 189-198.

Westerik N. 2020. Locally produce probiotic yoghurt for better nutrition and increased incomes in Uganda. PhD thesis, Free University of Amsterdam, The Netherlands.

Reid G, Kort R, Alvarez S, Bourdet- Sicard R, Benoit V, Cunningham M,  Saulnier DM, van Hylckama  Vlieg JET, Verstraelen H, Sybesma W.  Expanding the reach of probiotics through social enterprises. Beneficial Microbes, 9 (5): 707-715.

YOGURITO –the Argentinian social program with a special yogurt

 

 

 

New Spanish-language e-book about fermented foods now available for download

/in News, Consumer Blog /by KC

By Dr. Gabriel Vinderola, PhD,  Associate Professor of Microbiology at the Faculty of Chemical Engineering from the National University of Litoral and Principal Researcher from CONICET at Dairy Products Institute (CONICET-UNL), Santa Fe, Argentina

Fermented foods and beverages such as yogurt, wine, beer, kefir, kombucha, kimchi, and miso are created with the help of microbes. After more than 10,000 years of practice around the globe, fermentation has finally caught massive attention from a general public interested in knowing more about the fascinating, invisible world of microbes. In essence, the act of fermentation places food in a unique place between raw and cooked. The flavours, tastes, textures and potential health benefits of fermented foods, made possible through the presence of viable or non-viable microbes and their metabolites, are achieved through this set of ancestral food processing techniques. Today’s science allows us to see the functions of fermentation microbes that can make certain nutrients more bioavailable in foods. Fermentation can also reduce certain anti-nutrients and generate a large number of potentially beneficial microorganisms.

To help people learn about fermented foods, I was pleased to collaborate on an e-book with Ricardo Weill, an Argentinian dairy industry expert who first introduced Lactobacillus rhamnosus GG in Argentinian fermented milks in the 1990s, and Alejandro Ferrari, a biologist and scientific communications expert. The book is titled ‘Fermented Foods: microbiology, nutrition, health and culture’, and is currently available only in Spanish.

The book aimed to reach the general public, with scientific concepts but in easy-to-follow language for people with little or no previous knowledge of microbiology, nutrition or food technology. It tells the stories of many types of fermented foods around the world and adds a scientific perspective on their health benefits. The book brings together information from 38 authors from Argentina, Colombia, Japan, Spain and Finland, including ISAPP President Prof. Seppo Salminen, and Martin Russo, a professional chef in Argentina who specializes in fermentation. The book includes the following sections:

Fermentation: An anthropological view

Variety of fermented foods in Japan and other East Asian countries, and the microorganisms involved in their fermentation

Introduction to the intestinal microbiota: its role in health and the disease

Consumption of probiotic fermented milk and its impact on the immune system

Fermented milks, yogurts and probiotics

Kefir and artisanal fermented foods

Fermented meat sausages: Contribution of lactic bacteria in global quality

Lactic fermentation of cereals and Andean ancestral grains

Fermented vegetables and legumes

Fermentation of fruit drinks and drinks

Yeasts in beer and baked goods

Role of fermented foods in diet

Role of lactic acid in the beneficial effects of fermented foods

Microbiological safety of fermented foods

Fermented foods and chronic non-communicable diseases: A narrative review of the literature

Fermentation and gastronomy: A cook among scientists, a scientist among cooks

This e-book initiative started in October 2019, when a symposium about fermented food was organized by the Danone Institute of the Southern Cone (DISC).

The Danone Institute of the Southern Cone (DISC) was founded in 2008, and it is the local chapter for Argentina, Chile and Uruguay of the Danone Institute International network, which gathers 14 Danone Institutes (13 local Institutes and 1 International) in 15 countries. All Danone Institutes are non-profit organizations, dedicated to non-commercial activities and promotion of science.

Since its foundation, the DISC has collaborated with more than 200 experts taking part in different projects, and has served as a collaborative meeting place to reflect with their peers—all of them remarkable scientists coming from different and complementary specialties, focusing on key aspects of public health linked to food.

See the link to our book here:

Fermented Food: Microbiology, Nutrition, Health & Culture. (2020)

See the ISAPP press release about this book in English and en español.

Some previously-produced nutrition books that are freely available in Spanish on the DISC website are:

  • Impact of Growth and Early Development on the Population’s Health and Wellbeing. Perspectives and Reflections from the Southern Cone. (2009)
  • Healthy Growth. Between Malnutrition and Obesity in the Southern Cone. (2011)
  • The Role of Calcium and Vitamin D in Bone Health and Beyond. Perspective from the Southern Cone. (2013)
  • Methodologies Employed in Food Evaluation. An Ibero-American Vision. (2015)
  • Their Impact in Nutrition and Health. A Vision from the Southern Cone. (2018)

Hear from ISAPP board members in webinar covering probiotic and prebiotic mechanisms of action

/in Consumer Blog, News /by KC

This webinar is now complete — see the recorded version here.

New probiotic and prebiotic trials are published all the time – but when they show a health benefit, what do we know about the basic science behind it?

To provide insight into this topic, ISAPP has partnered with the International Life Sciences Institute (ILSI) Europe on a free webinar titled Understanding Prebiotic and Probiotic Mechanisms that Drive Health Benefits. This webinar helps scientists, members of the public, and media take a deep dive into what we know about the mechanisms of action of probiotics and prebiotics.

The live webinar is scheduled for Thursday, September 17, 2020 from 3 – 4:15pm Central European Time.

Short, 10-minute perspectives will be provided by the following top experts:

  • Prof. Sarah Lebeer, University of Antwerp, Belgium
  • Prof. Colin Hill, University College Cork, Ireland
  • Prof. Karen Scott, University of Aberdeen, UK
  • Prof. Koen Venema NUTRIM School of Nutrition and Translational Research in Metabolism, Venlo, The Netherlands

The presentations will be followed by a 35-minute live Q&A session, enabling participants to probe deeper into the science behind mechanisms of probiotics and prebiotics.

ILSI Europe is a non-profit organization that aims to improve public health and well-being from a science-based approach.

To learn more about probiotic mechanisms of action in advance of the webinar, see ISAPP’s blog post here.

¿Cómo permanecen vivos los probióticos hasta el momento de ser consumidos?

/in Consumer Blog /by KC

Por Gabriel Vinderola, Dr. en Química, Investigador Principal del Consejo Nacional de Investigaciones Científicos y Técnicas (CONICET) en el Instituto de Lactología Industrial (INLAIN, CONICET-UNL) y Profesor Asociado de la Facultad de Ingeniería Química de la Universidad Nacional del Litoral.

Como docente-investigador, la mayor parte del tiempo se comparte con personas del ambito académico y científico. Pero a través de las actividades de divulgación, tengo también la posibilidad de interactuar con personas que no tienen formación en ciencias, pero que tienen curiosidad por el mundo científico. Una pregunta que me hacen a menudo es: “¿Es posible que los probióticos sigan vivos cuando están deshidratados y en una cápsula?” La respuesta es sí. Permítanme proporcionar algo de información básica sobre los probióticos y explicar mi respuesta.

La idea de consumir microbios vivos para promover la salud no es nueva. En 1907, Élie Metchnikoff, discípulo de Louis Pasteur, el padre de la microbiología, asoció el consumo de leches fermentadas que contenían lactobacilos vivos, con una vida prolongada y saludable en campesinos búlgaros (see here). Esta idea fue retomada más tarde por el concepto de probióticos: microorganismos vivos que, cuando se administran en cantidades adecuadas, confieren un beneficio para la salud del huésped (Hill et al. 2014). Son cuatro criterios sencillos y pragmáticos los permiten concluir si determinadas cepas de microorganismos reúnen las condiciones para ser consideradas probióticos. Los probióticos deben: i) estar correctamente identificados (género, especie, cepa); ii) ser seguros para el uso previsto; iii) estar respaldados por al menos un ensayo clínico en humanos que demuestre su eficacia; y iv) estar vivos en el producto, y en cantidades suficientes para ser eficaces, durante todo el período de conservación (Binda et al. 2020). Estar viables en el momento del consumo es una de las características clave de los probióticos.

La vida es la condición que distingue a los animales y las plantas de la materia inorgánica. La vida implica actividad metabólica y la capacidad de crecer y reproducirse. Para que la vida sea posible, deben darse ciertas condiciones ambientales, las cuales difieren para los distintos organismos. Para los microorganismos en general, la disponibilidad de agua y nutrientes, la temperatura adecuado y la ausencia de inhibidores de crecimiento (como la acidez o los antibióticos) son condiciones esenciales para su desarrollo. Sin embargo, es posible manipular ciertas condiciones para lograr un estado en el que el crecimiento puede ponerse en “stand-by”, pero el microorganismo seguirá vivo. Nosotros los humanos no podemos imaginarnos en una condición “en modo de espera”, en la que estemos vivos aún sin ninguna actividad metabólica, pero para los microbios esto sí es posible. Los probióticos pueden estar en alimentos (ciertos yogures, jugos de fruta, barras de cereales) o en suplementos alimenticios (cápsulas, píldoras, sachets) en un estado de “hibernación”, caracterizado por la ausencia de crecimiento, de reproducción, en espera a que se den las condiciones adecuadas para retomar la actividad metabólica. Esto último ocurre cuando los probióticos llegan al intestino, donde encuentran la temperatura adecuada, los nutrientes necesarios, la ausencia de inhibidores y el agua necesaria para retomar su actividad metabólica. Por lo tanto, en el caso de los microorganismos, hay una disociación de la vida y la actividad metabólica. Incluso sin tener ninguna actividad metabólica, pueden seguir vivos, pero en un estado de latencia.

Al abrir un suplemento alimenticio que contenga probióticos, probablemente encontraremos un polvo seco blanco. Así es como los microorganismos pueden estar en un estado de latencia, debido a un proceso tecnológico llamado liofilización. La liofilización es un proceso de dos etapas en el que las células primero se congelan rápidamente a temperaturas muy bajas (de -40 a -70°C, o menos, utilizando nitrógeno líquido, por ejemplo). Luego, el agua congelada se elimina mediante un proceso de evaporación a baja presión y baja temperatura, llamado sublimación. Este proceso elimina la mayor parte del agua de las células, dejando a los microorganismos en un estado de inactividad o latencia. La actividad de agua es la forma en que los científicos miden la disponibilidad de agua para los probióticos. Esta medida tecnológica oscila entre 0 (sin disponibilidad de agua) y 1 (con total disponibilidad agua). Una actividad de agua cercana a 0 impide el crecimiento. En los suplementos dietarios, la liofilización deja la actividad de agua en un valor menor a 0,2, lo que asegura que no se produzca actividad metabólica durante la vida útil del producto.

Células de un probiótico constituido por bifidobacterias liofilizadas (indicadas por un círculo rojo). Esta es una imagen de microscopía electrónica de barrido amplificada 10.000 veces. Las células están incrustadas en una matriz de polidextrosa deshidratada, sin agua.

Así es que sí, los probióticos en los suplementos alimenticios están vivos, a su manera. Este es el caso también de los probióticos incluidos en ciertos alimentos como barras de cereales. En el caso de alimentos con actividades de agua más cercanas a 1, como los yogures, las leches fermentadas, los quesos o los jugos de fruta que contienen probióticos, el factor que limita la actividad metabólica es la baja temperatura a la que se conservan estos productos, combinada en ciertos casos (como los yogures y jugos de fruta) con el bajo pH (o alta acidez) de estos productos. La combinación de baja temperatura y acidez es eficaz para mantener a las células probióticas en un estado de latencia, lo que impide la actividad metabólica que pueda provocar estrés celular y muerte a lo largo de la vida útil del producto. Sin embargo, aunque se controlen estrictamente los factores que impiden la actividad metabólica durante la conservación, puede producirse cierta pérdida de viabilidad celular durante la vida útil de los probióticos en los productos que los contienen. En este caso, se agregan cantidades adicionales de probióticos para que la concentración de células viables necesaria para proporcionar un efecto benéfico sea la adecuada hasta el final de la vida útil del producto.

En los alimentos y suplementos probióticos, el número de células viables se expresa comúnmente como un número de unidades formadoras de colonias, abreviado “UFC”. Como los probióticos están presentes en altas concentraciones, el número de células viables suele alcanzar los miles de millones dentro de una cápsula o en una porción de yogur. Para poder contar un número tan grande de células, los microbiólogos deben hacer diluciones sucesivas del producto probiótico. Luego, pondrán una pequeña gota de las mayores diluciones en la superficie de una placa de Petri que contiene un medio de cultivo en el que crecerán los probióticos. Cada célula probiótica (o grupo de células) es una unidad formadora de colonias, que crecerá en su lugar y formará una colonia visible que puede ser observada a simple vista, y contada.

Placa de medio de cultivo que contiene colonias de una bacteria probiótica. Las células depositadas en la superficie del medio de cultivo se duplicaron varias veces hasta formar una cantidad visible de células: una colonia.

En síntesis, los probióticos están presentes en los alimentos y suplementos como cultivos vivos, pero en un estado de vida diferente al de los organismos superiores. Durante la vida útil de los probióticos, la actividad metabólica se detiene mediante la liofilización (en el caso de suplementos alimenticios) o mediante una combinación de baja temperatura y acidez (en el caso de yogures y jugos de fruta con probióticos, por ejemplo). El crecimiento activo de los probióticos suceso otra vez cuando estos microorganismos entran en el intestino y encuentran las condiciones adecuadas de nutrientes, temperatura, acidez y agua para estar activos y producir sus efectos benéficos sobre la salud.

How do probiotics stay alive until they are consumed?

/in Consumer Blog, ISAPP Science Blog /by KC

By Prof. Gabriel Vinderola PhD,  Associate Professor of Microbiology at the Faculty of Chemical Engineering from the National University of Litoral and Principal Researcher from CONICET at Dairy Products Institute (CONICET-UNL), Santa Fe, Argentina

See the Spanish version of this blog post here.

As a professor, most of my days are spent with people from the academic and scientific world. But through some outreach activities, I am also fortunate to interact with many people who are not scientists by training, but have curious, scientific minds. One question I am often asked is, “Is it really possible for probiotics to still be alive when they are dried and in a capsule?” The answer is yes. Let me provide some basic background on probiotics and explain my response.

The idea of consuming live microbes to promote health is not new. Back in 1907, Élie Metchnikoff, a disciple of Louis Pasteur, the father of microbiology, associated the intake of fermented milks containing live lactobacilli, with a prolonged and healthy life in Bulgarian peasants (see here). This idea was later captured by the concept of probiotics: live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (Hill et al. 2014). Four simple and pragmatic criteria allow one to conclude if specific strains of microorganisms qualify as a probiotic for use in foods and dietary supplements. Probiotic strains must be (i) sufficiently characterized; (ii) safe for the intended use; (iii) supported by at least one human clinical trial showing they are effective; and (iv) alive in the product at an efficacious dose throughout shelf life (Binda et al. 2020). Being alive at the moment of consumption is one of the key characteristics of probiotics.

Life is the condition that distinguishes animals and plants from inorganic matter. Life includes the capacity for growth, for reproduction and for metabolic activity. In order to sustain life, certain environmental conditions must be met, but these differ for different organisms. For microbes, the availability of water and nutrients, adequate temperature and pH (acidity), and the absence of growth inhibitors are essential conditions. However, it is possible to manipulate certain conditions to bring about a state where growth may be put in “stand-by mode”, yet the microbe remains alive. We cannot imagine ourselves in a condition where life is preserved even without any metabolic activity, but for microbes it is possible. Probiotics can be in foods (yoghurts, fermented milks, fruit juices, cereal bars) or in food supplements (capsules, compressed pills) in a “hibernation” state, characterized by no growth, no reproduction and no metabolic activity, waiting for the proper conditions to come back to full metabolic life. This occurs when the microbes reach the gut, which has proper temperature, nutrient availability, lack of inhibitors, adequate acidity and water. Thus, in case of microbes, there is an uncoupling of life and metabolic activity. Even without having any metabolic activity, they can still be alive, but in a dormant state.

Open a food supplement containing probiotics and you will probably find a white dry powder. This is what the microbes may look like in their dormant state, due to a technological process called freeze-drying or lyophilization. Freeze-drying is a two-stage process where cells are first quickly frozen at very low temperatures (-40 to -70°C, or less, using liquid nitrogen for example). Then, frozen water is removed by a gentle process of evaporation at low pressure and temperature, called sublimation. This process removes most of the water from around and inside the cells, leaving the microbes in a dormant state. Water activity is scientists’ way of measuring water availability for the microbes. This technological measure ranges from 0 (no water) to 1 (pure water). A water activity close to 0 impairs growth. In food supplements, freeze-drying leaves water activities less to 0.2, ensuring that no metabolic activity will take place during the shelf life of the product.

Bifidobacteria cells (circled in red) freeze-dried in a probiotic powder. This is a scanning electron microscopy image amplified 10,000 times. Cells are embedded in dry polydextrose.

So yes, probiotics in food supplements are alive in their own way. This is the case also for probiotics included in certain foods such as cereal bars. In case of food products with water activities closer to 1, such as yogurts, fermented milks, cheeses or fruit juices containing probiotics, the factor that limits metabolic activity is the low temperature at which these products are stored, combined in certain cases (yogurts, fermented milks, fruit juices) with the low pH (or high acidity) of these products. The combination of low temperature and acidity is effective in maintaining probiotic cells in a dormant state, impairing any metabolic activity that may lead to cell stress and cell death along the shelf life of the product. Yet, even while tightly controlling factors that impair metabolic activity, some cell death may occur during the shelf life of probiotics in the products that deliver them. In this case, responsible manufacturers are sure to add extra probiotic cells so that the necessary amount of viable cells needed to deliver a health effect are present through the end of the shelf life of the product.

In both probiotic foods and food supplements, the number of viable cells is commonly expressed as a certain number of colony forming units, or by the abbreviation “CFU”. As probiotics are present in high concentrations, the number of viable cells often reaches into the billions within a capsule or in a serving of yogurt. To be able to count such enormous numbers of cells, microbiologists must make serial dilutions of the probiotic product. Then, they will put a small drop of a dilution on the surface of a Petri dish containing a culture medium on which probiotics will grow. Each probiotic cell (or clump of cells) will grow in place and form a visible colony that can be observed to the naked eye, and counted.

Agar plate containing colonies of a probiotic bacteria. Cells deposited on the surface of the agar plate duplicated several times until forming a visible amount of cells: a colony.

In brief, live probiotics are present in food and supplements, but in a state of life different to that of higher organisms where metabolic activity is taking place at all times. During shelf life, the metabolic activity of probiotics is stopped by freeze-drying them (food supplements) or by a combination of low temperature and acidity (yogurts and fruit juices, for example). Active growth returns when these microbes enter out gut and find the proper conditions of nutrients, temperature, acidity and water to be active and deliver their health effects.

GG + BB-12 don’t reduce antibiotic use in an elderly, institutionalized population

/in Consumer Blog, ISAPP Science Blog /by KC

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

Close to two years ago, a team convened by ISAPP conducted a meta-analysis showing that probiotics may reduce number of antibiotic prescriptions, with evidence primarily in children (ISAPP-initiated systematic review and meta-analysis shows the association of probiotic consumption with reduced antibiotic prescriptions). A recent study suggests that this outcome likely does not extend to elderly care home residents.

A newly published randomized, placebo-controlled trial tested a combination product comprising two well-studied probiotic strains, Lacticaseibacillus (formerly known as Lactobacillus) rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12, administered at ~1.5 × 1010 per day to institutionalized residents 65 years of age or older to test if this treatment reduced antibiotic administration. The study showed no reduction in antibiotic use compared to the control. Further, the probiotic was not associated with improvement in secondary endpoints, which included many that probiotics are hypothesized to mitigate, including incidence of common infections, duration of infections, C. difficile infection, antibiotic associated diarrhea, hospitalizations, or presence of antibiotic resistant microbes in fecal samples.

Other endpoints suggested that the probiotic group fared worse than the placebo group. Statistically significant differences were found between the probiotic and placebo groups for antibiotics administered for lower respiratory tract infections and well-being scores at 3 months.

This was a well-controlled, comprehensively reported study.  Some factors to consider in interpreting these results:  The population was elderly (mean age = 85.3 years) and infirmed (66% lacked capacity to consent and 63 of 310 randomized subjects died prior to conclusion of the study). Stool culture at 3 months showed L. rhamnosus present in 84% of intervention group compared to 37% of placebo group, although the groups were matched for this factor at baseline. This suggests some cross-contamination between the placebo and intervention groups may have occurred. As the authors state, exposure of the placebo group to the probiotic “would dilute any between-group differences in outcomes.” A higher number of C. diff positive subjects were assigned to the probiotic group than the placebo group (7.2% vs 0%, respectively).

Overall, this study provides evidence that L. rhamnosus GG + B. lactis BB-12 are not effective prophylactically in a population of elderly care home residents.

 

Bulgarian yogurt: An old tradition, alive and well

/in Consumer Blog, ISAPP Science Blog /by KC

By Mariya Petrova, PhD, Microbiome insights and Probiotics Consultancy, Karlovo, Bulgaria

Family and family traditions are very important to me. Some of you may have seen my previous blog post on fermented food and my father’s tradition of making fermented cabbage and vegetables every autumn. Of course, this is not limited to my family – in Bulgaria, it is our culture and our country’s tradition. But despite the fact that I wrote about fermented vegetables first, Bulgarians are much more proud of another fermented product – yogurt.

I still remember waking up every morning when I was a kid and having a healthy homemade yogurt to start the day. I still do when I am back at home, because my father continues to make yogurt at home. Here, I’ll take you on a new adventure and tell you all about Bulgarian yogurt, an old tradition still alive in every home.

Élie Metchnikoff and his work are well familiar to anyone involved in probiotic research. In short, Metchnikoff observed in 1907 that Bulgarian peasants lived longer lives and he attributed this to their daily consumption of yogurt.

Thanks to Metchnikoff, research on Bulgaria and Bulgarian yogurt was put on the map because of our healthy way of living and eating fermented foods. You may know this part of the story. Still, few actually know that Metchnikoff was intrigued by the work of the Bulgarian researcher Stamen Grigorov a few years earlier. In fact, it was because of Stamen Grigorov’s work that we now know ‘who’ (i.e. which microbes) live in our yogurt and how essential those tiny bacteria are. In 1905 Stamen Grigorov actually discovered and isolated for the first time Lactobacillus bulgaricus (now known as Lactobacillus delbrueckii subsp. bulgaricus) from homemade yogurt. That’s why we are so proud of Bulgarian yogurt. Not only do we love to eat it, but the probiotic research was partially initiated in our country, and an entire Lactobacillus species is named after our country. There is even a small museum dedicated to Bulgarian yogurt and to the work of Stamen Grigorov, located in the house where he was born. In the museum, if you are visiting Bulgaria, you can learn how to make yogurt at home and a bit more about the history of Grigorov’s discoveries.

We are so proud of our yogurt that many Bulgarians will tell you that ancient Bulgarian tribes were the ones who discovered yogurt by accident. Since Bulgarian tribes were nomadic, they carried the milk in animal skins, which created an environment for bacteria to grow and produce yogurt. This is indeed the way people learned to make yogurt, but it most likely happened in many places independently. Of course, I know many countries make yogurt but I remain proud of all the discoveries that happened in my country (I am saying this because at times I have been judged when I tried to say how important we find the yogurt in Bulgaria and how proud we are).

Yogurt is a tradition in Bulgaria. I don’t know a Bulgarian who does not eat yogurt on a daily basis, up to a few pots per day. And I am not talking about those sweet yogurt products that are made by adding jam or vanilla. I am talking about real, natural yogurt, slightly sourer than most of the products that can be found in the Western world. We add yogurt to almost everything, it is just the perfect addition. It is even the basis of a traditional Bulgarian cold summer soup called “tarator,” made of yogurt, water, cucumber, garlic, and dill. We also make a salad with it called “snezhanka”, and it contains yogurt, cucumbers, garlic, and walnuts. (Recipes can be found below if you want to try something new during the lockdown.) In fact, I am so “addicted” to our yogurt that in every country I go to, the first thing I have do is to find a good yogurt. It took me years to find a good one in Belgium when I lived there (even though one product was labelled ‘Bulgarian yogurt’, it was not the same for sure). In Canada, it was somehow easier. After trying a few different products, it was even faster to find something that I like in the Netherlands, but they have many kinds of milk products. Yet none of them are truly comparable with what you can find in Bulgarian shops. Even the smallest shops have at least 3 to 4 different types because we have a lot of yogurt factories. Every product is different, it has a unique taste and can be made of different kinds of milk.

But honestly, nothing is the same as the homemade yogurt. Many people still make yogurt at home, including my father. I don’t quite remember a time when there was no homemade yogurt on the table at home. It was initially my grandmother making the yogurt and the white Bulgarian cheese (it is nothing to do with Feta but that’s the closest way to explain what it is). So it was somehow logical that my father started making yogurt as well. He knows the technique from his grandmother and grew up with fresh homemade yogurt. My grandparents had a lot of cows, sheep, and goats, so we always had plenty of milk to ferment. Making yogurt at home is so very simple that more and more young people dare to do it. In fact, making yogurt is so easy, I wonder why I am not doing it myself during the lockdown.

How to make it, you may ask?

So you need fresh milk, which my family in Bulgaria currently gets from a local farm. The milk is carefully boiled, and while it is still warm, transferred to a preferable container where you want to make the yogurt. We use old yogurt jars that were very popular before. For some time, my father also used Tupperware, so you can choose anything that you find handy. Before transferring the milk, my father also separates the cream from the milk in a separate jar and uses it to make homemade butter by constantly shaking the jar for around 10 minutes (it is an intensive workout, I tried it a few times!). The biggest problem these days is having a good starter culture so you can begin the milk fermentation. As a starter culture, most of the people, including my father, use a spoon or two of the previous batch of yogurt. So my father never finishes all the yogurt; he always makes sure that there are some leftovers so he can start a new fermentation. He usually adds one tablespoon of the old yogurt to 500 ml warm milk (around 45 C). Of course if the milk is too hot, the bacteria present in the starter culture will die, and nothing will happen. There is also the case that the milk is too cold, and then it will most likely still ferment, but it will have a strange consistency, something between milk and yogurt. If my father is out of old yogurt to start a new fermentation, he usually buys his favorite yogurt from the shop and uses this as starter. Once the jars are filled, he packs blankets all around them to keep the environment warm so the fermentation will begin. From here, you need around 4h to 5h to have a nice homemade yogurt. Simple and straightforward. The next morning you can have a great family breakfast, remembering the old traditions, talking about old memories, passing on the torch to the new generation, and enjoying a healthy start to the day.

The next time you have yogurt, I hope you enjoy it and remember the Bulgarian traditions!

 

Tarator soup recipe:

What you need: 1 cucumber, 250 -300 g yogurt, 1-2 cloves crushed garlic, salt, oil, water, fresh chopped dill. (Most of the ingredients depend on your taste so feel free to add more or less of certain ingredients. Some people also add parsley and walnuts, but it is up to your taste.)

How to make it: Peel and cut the cucumbers into cubes and put them in a preferred bowl; add the crushed garlic, and the minced dill. Beat the yogurt until it turns to liquid and mix it with the rest of the ingredients. Add salt and oil to taste. Add water to make the soup as liquid as you like. Put into the refrigerator to cool it. You can also make it with cold yogurt and cold water. It is perfect for the hot summer days.

Snezhanka (which means “Snow White” in Bulgarian) salad recipe:

What you need: 1 cucumber, 500 g yogurt, 1-2 cloves crushed garlic, 2-3 spoons ground walnuts, salt, oil, fresh chopped dill. (Again, it depends on your taste, if you like more cucumber or yogurt just add more.)

How to make it: First strain the yogurt for a couple of hours, so that all unnecessary water is drained away. Peel and cut the cucumbers into cubes and put them in the bowl. Add the strained yogurt. Add the fresh dill, salt and oil to taste. Sprinkle the walnuts on top of the salad. Perfect for all seasons. If you don’t have a fresh cucumber, you can also use pickles — the final result is also very delicious.

Are prebiotics good for dogs and cats? An animal gut health expert explains

/in Consumer Blog, ISAPP Science Blog /by KC

By Kelly S. Swanson, PhD, The Kraft Heinz Company Endowed Professor in Human Nutrition, University of Illinois at Urbana-Champaign, USA

Pet dogs and cats are cherished companions. In developed countries, many households with pets treat them like family members. Similarly to humans, a high level of nutrition and veterinary care promotes health and longevity. As people become more aware of what they feed themselves and their human family, they make the same considerations for their canine and feline companions. Pet food trends have closely followed those of the human food industry over the last couple decades, with high-quality natural and organic foods gaining popularity.

One way pet food companies have enhanced their products is by incorporating functional ingredients into their formulas. Functional ingredients provide benefits beyond that of their nutrient content. One of the most popular target areas for functional ingredients is pet gastrointestinal health, with structure/function claims of “supporting digestive health”, or something similar, being quite common. Loose stools, constipation, and various gastrointestinal disorders and diseases such as inflammatory bowel diseases and irritable bowel syndrome are common in pets. The task of “poop scooping” after the dog in the park or cleaning out the cat’s litterbox provides owners with an opportunity for daily assessment of stool quality and serves as a reminder of how important diet is to gut health.

Benefits of prebiotics for pets

Many ingredients, including dietary fibers, prebiotics, probiotics, synbiotics, postbiotics, and other immunomodulators may provide gastrointestinal benefits to pets, but today we will focus on prebiotics. The most recent ISAPP expert consensus panel on prebiotics clarified that the prebiotic concept not only applies to humans, but also to companion and production animals (Gibson). Dogs and cats evolved as Carnivora, mainly consuming high-protein, high-fat diets that were low in fiber, and their short, simple gastrointestinal tracts have a limited capacity to ferment non-digestible substances. Nonetheless, they possess an active microbiota population, primarily in the colon, that may be manipulated by diet to impact health.

Most prebiotic research in pets has focused on the gastrointestinal tract. Prebiotic administration has been shown to reduce the incidence or severity of infections (Apanavicius; Gouveia), improve stool consistency (Kanakupt), and beneficially shift fecal microbiota and metabolite profiles (Propst). A few have reported the benefits that prebiotics may have on metabolic health, demonstrating improved glucose metabolism and insulin sensitivity in pets consuming prebiotics (Respondek; Verbrugghe). Since we’re looking at foods rather than at medicines that address disease, the majority of research has been conducted in healthy animals so evidence of health improvements in diseased pets is sparse.

Types of pet-friendly prebiotics

Although a few studies have tested galactooligosaccharides (GOS), mannanoligosaccharides, and other potential prebiotics, by far the most common prebiotics studied and present in pet foods are the non-digestible fructans. Natural sources, such as chicory, or isolates and extracts that have a high purity, including short-chain fructooligosaccharides (FOS), oligofructose, and inulin, are all present in pet foods.

Which pets benefit most?

Similar to dietary fiber, the need for prebiotic inclusion is dependent upon diet type and formulation. Animals consuming plant-based diets that are rich in natural fibers and non-digestible oligosaccharides likely do not require additional fermentable substrate in the formula. Dogs and cats fed high-protein, meat-based diets, however, typically have greater fecal odor, a higher colonic pH, and higher density of potential pathogens due to a high rate of protein fermentation. In those diets, prebiotic inclusion may help animals normalize their gut microbiota abundance and metabolism.

Prebiotics may be fed to all pets, but will likely provide the greatest benefits to geriatrics, animals who are or have received antibiotics, those under high stress conditions, or those with certain gastrointestinal disorders. The low caloric density of prebiotics and the metabolic benefits that come from their fermentation will be most beneficial to pets with obesity and diabetes. As for all functional ingredients, dosage is important. When comparing dogs and cats, dogs usually can tolerate a higher dosage than cats. In regard to dog size, small dogs can typically tolerate a higher dosage (per unit body weight) than large dogs, which are more susceptible to loose stools. In most commercial pet foods, prebiotic inclusion levels are <0.5% of the formula to limit side effects.

Further research on prebiotic substances

Using the powerful tools that are now available to study gut microbiota and host physiology, future research can hopefully determine what microbes are most important to the health of dogs and cats and identify mechanisms by which prebiotics provide health benefits to pets. Further testing, which may include plant-based ingredients, yeast-based products, and milk oligosaccharide mimics, will hopefully identify other prebiotic substances and continue to expand our knowledge in the field.

 

Kelly Swanson joined the ISAPP board of directors in June, 2020, providing valuable expertise in animal gut health and overall health. Swanson also chaired the 2019 ISAPP-led international consensus panel on the definition of synbiotics.

 

 

 

What makes a synbiotic? ISAPP provides a sneak peek at the forthcoming international scientific consensus definition

/in Consumer Blog, ISAPP Science Blog /by KC

By Kristina Campbell, science and medical writer

The word ‘synbiotic’ is found on the labels of many different products, from supplements to chocolate bars, and it has generally been understood to be a combination of a probiotic and a prebiotic. But what happens when scientists want to test whether these combination products really deliver any health benefits? Can these products be tailored to have specific effects on the body or on the human gut microbiota? Agreeing on a clear definition of synbiotics is needed to provide focus for scientific research in this area, to facilitate the design of studies, and to allow for progress wherein their health effects are uncovered.

The scientific definition of synbiotic was the central topic of the international scientific panel brought together by ISAPP in May 2019 in Antwerp, Belgium. Members of the panel, eleven of the top academic experts in the field of probiotics and prebiotics, gathered to clarify a scientifically valid approach for use of the word ‘synbiotic’, and to communicate this by position paper. The outcome of this consensus panel is currently in press at Nature Reviews Gastroenterology & Hepatology.

Kelly Swanson, Professor in the Department of Animal Sciences and Division of Nutritional Sciences at University of Illinois at Urbana-Champaign, chaired the panel and led the paper’s publication. Swanson has been studying gastrointestinal health in both humans, companion animals (dogs and cats) and rodent models for the past 20 years—and having followed the rapid advances in the field of probiotics and prebiotics during those two decades, he knew the task of creating a synbiotic definition would not be easy.

He says, “The field is highly complicated, so an interdisciplinary panel was essential. The main areas of expertise included microbiology and microbial ecology; gastrointestinal physiology; immunology; food science; nutritional biochemistry and host metabolism.”

A timely discussion

According to Swanson, an increase in research interest, built on a foundation of recent scientific and technical gains, made this the right time to come to consensus on a synbiotic definition. He says, “Over the past decade, technological advances have allowed scientists to study the gut microbiome at a molecular level. In addition to characterizing the composition of the gut microbes, researchers are learning more about their biological activity and how they may impact host health.”

Furthermore, clarity about the definition was urgently needed because of the rapidly growing synbiotics market. Consumers seem to be more aware of synbiotics than ever, but they face a bewildering array of product offerings labeled as ‘synbiotic’ without a clear understanding of what that term entails and with no framework for establishing scientific efficacy. Swanson says, “As the field has moved forward and the sales of probiotics and prebiotics have increased, there has been more interest in combining substances to enhance efficacy. Some of these combinations may function as synbiotics, but it is not guaranteed. Rather than randomly combining substances together, there should be scientific rationale supporting their use.”

Clarifying the concept

One of the first questions the panel members had to tackle was whether to stick to the idea of a synbiotic as ‘probiotic plus prebiotic’, thus leaning heavily on the ISAPP-led international consensus definitions of probiotics and prebiotics published in 2014 and 2017, respectively. But the panel members decided this narrow scope would ultimately limit innovation in the synbiotic category.

Swanson explains, “While many synbiotics may be composed of an established prebiotic and established probiotic, the panel did not want to restrict scientific advances in the synbiotic category by requiring use of components already established on their own.”

As a result, he says, previously untested live microbes and potential prebiotic substances could be considered a synbiotic if the combination showed efficacy, and if the health benefit came from administering both the live microbe and the substrate it utilized—that is, the microbe together with its ‘food’.

Another conclusion from the panel is that probiotics (with known health benefits) and prebiotics (with known health benefits) cannot be called synbiotics unless they have been tested together. “There should be a rationale supporting the combination used, and then testing of the combination to confirm its efficacy,” says Swanson.

The panel suggests a synbiotic may be composed of either of the following, as long as efficacy is demonstrated for the combination:

  • Established probiotic + established prebiotic (each component meeting the efficacy and mechanistic criteria for each)
  • Previously untested live microbe + a substrate that is selectively utilized by the co-administered live microbe

Further details, including two different ‘categories’ of synbiotics, will be provided in the published paper.

In addition to the definition, the publication will cover the history of synbiotic-type products, how these products can be characterized, levels of evidence that currently exist versus levels of evidence desired, points about safety documentation and reporting, and relevant characteristics of the target hosts.

A remaining challenge—not just for the expert group, but also across the field—is the difficulty of establishing causal links between substances’ effects on the gut microbiota (e.g. ‘selective utilization’ of a substrate) and health outcomes.

While the publication of the synbiotic definition will be an important milestone, Swanson anticipates further discussion in the years ahead. “As more is learned, I expect the criteria for assessing synbiotic efficacy will continue to change,” he says.

An update on the scientific consensus definition of synbiotic was presented to ISAPP members at the 2020 virtual meeting in June.

 

ISAPP partners with British Nutrition Foundation for fermented foods webinar

/in Consumer Blog, News /by KC

Did you miss the live webinar? Access the archived version here. Read the speaker Q&A here.

From sourdough starter tips to kombucha flavor combinations – if you’ve checked a social media feed lately, you’ll know how many people are sharing an interest in fermented foods as they self-isolate during the pandemic. And with this rise in popularity comes a host of questions about the practice and the science of fermented foods.

To meet the need for science-based information about fermented foods, ISAPP has partnered with the British Nutrition Foundation (BNF) on a free webinar titled ‘Fermented Food – Separating Hype from Facts.’ The BNF is a UK-based registered charity that brings evidence-based information on food and nutrition to all sectors, from academia to medicine.

The webinar, designed for practicing dietitians and nutrition-savvy members of the public, featured three leading scientific experts who explained the microbiology of fermented foods, the evidence for their health effects, and who might benefit from making these foods a regular part of the diet. Viewers will come away with a clear understanding of what fermented foods are and what evidence exists for their health benefits.

The webinar was held live on Wednesday, July 1, 2020 from 1pm-2pm (BST).

Webinar speakers & topics

 Understanding fermented foods: Dr. Robert Hutkins, University of Nebraska, USA

Exploring the evidence for effects of fermented foods on gastrointestinal health – how strong is it? Dr. Eirini Dimidi, Kings College London

What role can fermented foods have in our diet? A public health perspective, Anne de la Hunty, British Nutrition Foundation

For a quick primer on fermented foods, see the short ISAPP video here or the ISAPP infographic here.

[IN SPANISH] Creciente interés en Argentina en microorganismos benéficos y alimentos fermentados

/in Consumer Blog, ISAPP Science Blog /by KC

Dr. Prof. Gabriel Vinderola, Investigador Principal CONICET, Instituto de Lactología Industrial (INLAIN, CONICET-UNL), Profesor Asociado, Cátedra de Microbiología, Facultad de Ingeniería Química, Universidad Nacional del Litoral, Santa Fe, Argentina.

El interés sobre las bacterias intestinales, los alimentos fermentados y los probióticos está en aumento en Argentina y la región. Nutricionistas e influencers, que en los últimos años han comenzado a promover un estilo de vida más saludable, están aprovechando sus redes sociales para publicar recetas sobre cómo hacer alimentos fermentados, consejos para promover una microbiota más saludable e información sobre el posible papel de los probióticos y prebióticos en la salud humana. Pero, ¿están estas recomendaciones basadas en la ciencia? No siempre! En particular, he tenido la oportunidad de contribuir a que la comunicación sobre la microbiota, los alimentos fermentados, los probióticos y los prebióticos se haga desde la ciencia, para una audiencia amplia y con un leguaje simple.

En Argentina, y desde hace 50 años, hay un programa de televisión con un formato particular: la anfitriona, la Sra. Mirtha Legrand, cada domingo invita a almorzar a 4-6 personas para hablar, durante 3 horas, de política, economía, cultura popular, arte e incluso ciencia. Según ella, se trata del programa de televisión que se ha transmitido, ininterrumpidamente, por más tiempo en el mundo. Cada domingo, miles de personas de Argentina, Uruguay y Paraguay lo sintonizan. En octubre de 2019, me invitaron a unirme a la mesa y hablar sobre el mundo invisible que existe dentro y alrededor de nosotros. Discutimos cómo podemos beneficiarnos de las bacterias a través de alimentos fermentados y los probióticos, y cómo alimentar nuestros microbios intestinales con prebióticos. De hecho, en 2019, di más de 40 charlas sobre este tema a audiencias muy variadas a través de conferencias para profesionales, cursos para estudiantes de doctorado, seminarios y talleres para gente sin formación científica. Estas acciones están dirigidas no sólo a científicos y estudiantes, sino también a niños en escuelas, adolescentes en clubes deportivos y gimnasios o personal que trabaja en hospitales. El interés por los “bichos amistosos” es amplio y variado, y se alimenta de la información que circula por programas de radio y televisión.

“Almorzando con Mirtha Legrand”, un talk show que ha estado al aire en televisión por más de 50 años en Argentina, donde la discusión sobre microorganismos benéficos fue llevada a la mesa por Gabriel Vinderola (último a la derecha). Mirtha Legrand, de 93 años, está en el centro de los invitados (03/10/2019).

El entusiasmo de la audiencia fue inmediato. Se recibieron numerosos mensajes por correo electrónico, WhatsApp, Facebook o Instagram. La gente demostró estar interesada en saber más, preguntando por fuentes confiables para leer material con base científica, pero “fácil de entender”, planteando preguntas específicas sobre cuestiones intestinales, de dónde obtener probióticos y prebióticos o cómo hacer alimentos fermentados de manera segura. Afortunadamente, las infografías de la ISAPP sobre probióticos y prebióticos ya estaban disponibles en español, traducidas por Miguel Gueimonde (España) y por mí, y fueron un recurso muy utilizado. Sin embargo, la gente solicitaba más información, y hacía más y más preguntas específicas.

Estimulado por el creciente interés, me puse en contacto con una chef local, Ana Milena Giacomini, quien dejó atrás su carrera profesional de abogada para abrir un pequeño restaurante con un menú basado principalmente en alimentos fermentados. Ella ofrece sabrosos platos que incluyen yogur casero, chucrut, kimchi, kéfir de agua, humus fermentado, pan de masa madre, panqueques hechos de harina de arroz fermentada, kombucha, kvass y bebidas gasificadas a base de jengibre fermentado. Con ella organizamos talleres de 4 horas de duración, que actualmente están suspendidos debido a la pandemia por COVID-19. En estos talleres Ana prepara en vivo algunos de estos alimentos fermentados, para a continuación degustarlos, mientras yo explico la ciencia y la microbiología que hay detrás de ellos. Se discuten aspectos relacionados con la identidad, seguridad, estabilidad y los posibles efectos sobre la salud de estos productos. Siempre enfatizo las diferencias entre los alimentos fermentados y los probióticos, a la vez que discuto el potencial valor de incorporar alimentos fermentados, probióticos y prebióticos a la alimentación diaria como una forma de promover la salud intestinal. En estos talleres proporciono además información más específica sobre los efectos en la salud de probióticos para los que se dispone de sólidos meta-análisis que apoyan el uso de ciertos microorganismos en la prevención de la diarrea asociada a antibióticos en niños, el tratamiento de cólicos infantiles, la prevención de alergias y la reducción de la inflamación intestinal. Otros talleres con diferentes chefs de diferentes lugares de Argentina están en lista de espera para cuando esta pandemia de coronavirus termine.

Cena de cuatro pasos que incluye alimentos fermentados en cada plato, preparada por el chef argentino Martin Russo. La entrada consistía en zanahorias fermentadas y hummus, servidas en pan de masa madre.

En estos talleres se espera la asistencia de 30-35 personas cada vez. Entre ellas, nutricionistas interesados en dar respuestas adecuadas a sus pacientes, que se enteran de estos temas en los medios de comunicación o en las redes sociales. Pero también asisten personas que quieren aprender cómo hacer alimentos fermentados, dónde encontrar probióticos y prebióticos, u obtener una orientación clara sobre cómo incorporar bacterias vivas a su dieta. También asisten otros profesionales de la salud (gastroenterólogos, pediatras), docentes e incluso gente de la industria.

El postre eran bochas de helado cubiertas por la madre del vinagre (círculo transparente en la parte superior), enjuagadas y endulzadas.

La mayoría de los interesados en asistir a estos talleres tienen poca experiencia en alimentos fermentados, sólo están familiarizados con productos como el yogur, el queso, el vino o la cerveza. Es más, muchos de ellos desconocen que estos alimentos son fermentados, o no poseen una idea clara de lo que es la fermentación. La mayoría de ellos también tienen un conocimiento muy limitado, o incluso información errónea, sobre los probióticos y prebióticos. Estos talleres ofrecen la posibilidad de que personas interesadas en estos temas aprendan y prueben nuevos alimentos, de que conozcan la ciencia que hay detrás de los alimentos fermentados, los probióticos y los prebióticos, y de que aprendan las diferencias entre ellos de forma científica y en un “lenguaje fácil de seguir”. Estos encuentros son una forma de expandir el interés del público en general sobre el mundo invisible que habita dentro y alrededor nuestro.

Growing interest in beneficial microbes and fermented foods in Argentina

/in Consumer Blog, ISAPP Science Blog /by KC

By Prof. Gabriel Vinderola PhD, Associate Professor of Microbiology at the Faculty of Chemical Engineering from the National University of Litoral and Principal Researcher from CONICET at Dairy Products Institute (CONICET-UNL), Santa Fe, Argentina

Awareness of gut microbes, fermented foods and probiotics has been on the rise in Argentina. Nutritionists and influencers, who in recent years have begun promoting a healthier lifestyle, are leveraging their social networks to post how-to instructions for making fermented foods, advice to promote a ‘healthier’ microbiota, and information on the potential role of probiotics and prebiotics in human health. But are these news items and recommendations based on science? Not always! I’ve been fortunate to have had the opportunity to make sure the science is correctly communicated to a broad audience on the microbiome, fermented foods, probiotics and prebiotics.

In Argentina, for the last 50 years, there has been on the air a TV show with a particular format: the hostess, Miss Mirtha Legrand, invites 4-6 people to have lunch every Sunday, talking about politics, economy, popular culture, arts and even science for 3 hours. According to her, this is the longest continuously running TV program in the world. Every Sunday several thousands of people from Argentina, Uruguay and Paraguay tune in. In October 2019, I was invited to join the table and to comment about the invisible world inside and around us. We discussed how we can profit from bacteria through fermented foods and probiotics, and how to feed our gut microbes with prebiotics. In fact, in 2019, I gave more than 40 talks on this topic to scientific audiences at conferences, as courses for Ph.D. students, as seminars and as workshops. These efforts are targeted not only to local scientists and students, but also to children in schools, local sport clubs in small towns, gyms and hospitals. The interest in friendly bugs is wide-ranging and varied, and fueled by information from radio and TV programs.

“Having lunch with Mirtha Legrand”, a talk show on television for more than 50 years in Argentina, where the discussion on beneficial microbes was brought to the table by Prof. Gabriel Vinderola (far right). Mirtha Legrand, now 93 years old, is in the center (October 3rd, 2019).

The enthusiasm of the audience was immediately evident. Lots of messages came by email, WhatsApp, Facebook or Instagram. People were anxious to know more, inquiring about trustworthy sources to read scientific-based but “easy-to-understand” material, posing specific questions about their gut feelings, where to get these probiotics and prebiotics or how to make fermented foods in a safe manner. Fortunately, the ISAPP infographics on probiotics and prebiotics were already available in Spanish, translated by Miguel Gueimonde (Spain) and me, and these were a welcome resource. Yet people still wanted more information, and asked more and more specific questions.

Spurred by such widespread interest, I contacted a local lawyer-turned-chef, Ana Milena Giacomini, who left behind her professional law career to open a small restaurant with a menu heavily based on fermented foods. She features such delights as home-made yoghurt, chucrut, kimchi, sugary kefir, fermented hummus, sourdough bread, pancakes made out of fermented rice flour, kombucha, kvass and a gasified drink from fermented ginger. With her, we organized 4-hour workshops, which are currently on hold due to COVID-19. These workshops feature Ana preparing some of these fermented foods live, followed by tasting, while I explain the science and microbiology behind them. I share factors related to the identity, safety, stability, and potential health effects of these products. I emphasize the differences between fermented foods and probiotics, while discussing the potential value of incorporating fermented foods, probiotics and prebiotics to the daily diet as a way to promote gut health. I provide more specific information on health effects for which robust meta-analyses are available to support the microbes’ use, such as prevention of antibiotic-associated diarrhea in children, treatment of infant colic, prevention of allergies, and downregulation of intestinal inflammation. Other workshops with different chefs from different locations in Argentina are in line for when the coronavirus pandemic ends.

Part of the four-course dinner containing fermented foods prepared by chef Martin Russo. The starter consisted of fermented carrots and hummus, served on sourdough bread (pictured).

These workshops are expected to be attended by 30-35 people each time. Nutritionists are interested in giving sound responses to their clients, who hear about these topics in the media or in social networks. But also, people come who want to learn how to make fermented foods, where to find probiotics and prebiotics, or to gain clear guidance on how to incorporate live bacteria to their diets. Other health professionals (gastroenterologists, pediatricians), educators and even people from the industry also attend.

 

The dessert was ice cream balls covered by the mother of vinegar (transparent circle on the top), rinsed and sweetened.

Most people interested in attending these workshops have narrow experience with fermented foods, only being familiar with such things as yoghurt, cheese, wine or beer. Some of them do not know that these foods are indeed fermented, or do not have a clear idea what fermentation is about. Most of them also have a very limited awareness, or even misinformation, about probiotics and prebiotics. These workshops offer the possibility for the curious to learn and to taste new foods, to get insights on the science behind fermented foods, probiotics and prebiotics, and to learn the differences between them in a science-based manner in an “easy-to-follow language”. These encounters are a great way to expand the interest by the general public on the invisible world inside and around us.

The Horses: Daily Routines in the COVID-19 Era

/in Consumer Blog /by KC

By Gregor Reid BSc (Hons), PhD, MBA, ARM CCM, Dr HS, FCAHS, FRSC

It’s dawn and as per every day, I put on my mask. It’s not the type of mask you might think in these anxious times. It’s to prepare hay bags for our two horses. Hay, filled with the dust and mold particles that frankly my lungs despise.

After preparing the hay, I then begin my walk. Our faithful dog by my side in between racing after a ball that ejects from a plastic thrower in my right hand. All around, the sounds of birds starting their day in song, zooming in to find a spot on a feeder filled with sunflower seeds and nuts. The air is cool, but it opens my lungs.

 

In half an hour, I will go back to our house and open up a computer screen that counts the dead and the ill from around the world. That sends me a litany of messages outlining new rules and procedures. The temptation to check savings has long passed. Not that they don’t matter. It’s just that we have to cope whatever they do.

As I walk past bare trees standing tall, itching to come alive, I think of frontline workers at hospitals being asked to check incoming sickness. Surely, managers, teachers or others could take over this public-facing role? We need to protect front-line health workers, or we won’t have them by our bedside. I know of one case where a super-highly qualified nurse was thrust into the cold air without protective gear and told to check incoming. The managers hadn’t fully understood what a virus is, how it infects and what is needed to stop it, and despite advance warning from other countries they had left the hospital and staff unprepared. The nurse had to demand personal protective equipment. Thankfully, awareness is growing. The messaging is now full-on.

Isn’t it easy to fathom what we’re all scared of? The cough, the sore throat, the fever then lungs that can’t seem to get enough air into our body? The fear of our calls not being answered, of not getting tested, and where we sit on the priority list when the ventilators are all taken? The fear of not seeing your mother again because planes won’t take you there and she’s too old to be saved.

It’s the first day of spring, so the leaves have not yet shuttered the sounds of motor vehicles on nearby roads, except today that constant hum is muted. It’s quiet outside. Humanity behind curtains. As it should be, even though we could never have imagined it.

I sit down for breakfast. Oatmeal, a probiotic milk drink that has data on fighting the flu, on top of frozen fruit melted in the microwave. A tablespoon of sunflower seeds and almonds the birds didn’t get. I pop my favourite probiotic along with a multi-vitamin perhaps only to sanctify my mind. Plus, a cup of tea, of course.

I re-read what my colleague in Britain, Glenn Gibson, has compiled. A brilliant piece on why probiotics may help us fight this coronavirus. I also wrote a commentary, well-intentioned but already met with cynicism via Twitter, that communication tool that never allows enough space to say what needs to be said, and is never enough for the addicted users.

Whatever we do to fight this miniscule blob looking only to live and multiply like the rest of us, we must do it with hope. For hope is our salvation. It is what we aspire to find. And if our time here has come to an end when we least expected it, we can still leave hope for others and tell them we tried our best to shine a light in the darkness. A light that will be their future. And if more time is given to us, then surely with every ounce of energy we will welcome the horses and the blessings of Mother Nature and pass our multitude of gifts to make the world a better place.

 

When I was at high school, our English teacher from the highlands had us read a poem written around the year I was born (1955) by a famous Scot, Edwin Muir. It’s called The Horses and I will leave it for you to read (substitute ‘fathers’ for ‘parents’). For Muir, these beautiful animals were creatures closest to his God. Animals to bring hope through the hours of sadness and fear.

Barely a twelvemonth after
The seven days war that put the world to sleep,
Late in the evening the strange horses came.

By then we had made our covenant with silence,
But in the first few days it was so still
We listened to our breathing and were afraid.

On the second day
The radios failed; we turned the knobs; no answer.
On the third day a warship passed us, heading north,
Dead bodies piled on the deck. On the sixth day
A plane plunged over us into the sea. Thereafter
Nothing. The radios dumb;

And still they stand in corners of our kitchens,
And stand, perhaps, turned on, in a million rooms
All over the world. But now if they should speak,
If on a sudden they should speak again,
If on the stroke of noon, a voice should speak,
We would not listen, we would not let it bring
That old bad world that swallowed its children quick

At one great gulp. We would not have it again.

Sometimes we think of the nations lying asleep,
Curled blindly in impenetrable sorrow,
And then the thought confounds us with its strangeness.

The tractors lie about our fields; at evening
They look like dank sea-monsters couched and waiting.
We leave them where they are and let them rust:
‘They’ll molder away and be like other loam.’

We make our oxen drag our rusty plows,
Long laid aside. We have gone back
Far past our fathers’ land.

And then, that evening
Late in the summer the strange horses came.

We heard a distant tapping on the road,
A deepening drumming; it stopped, went on again
And at the corner changed to hollow thunder.

We saw the heads
Like a wild wave charging and were afraid.
We had sold our horses in our fathers’ time
To buy new tractors. Now they were strange to us
As fabulous steeds set on an ancient shield.
Or illustrations in a book of knights.

We did not dare go near them. Yet they waited,
Stubborn and shy, as if they had been sent
By an old command to find our whereabouts
And that long-lost archaic companionship.

In the first moment we had never a thought
That they were creatures to be owned and used.
Among them were some half a dozen colts
Dropped in some wilderness of the broken world,
Yet new as if they had come from their own Eden.

Since then they have pulled our plows and borne our loads
But that free servitude still can pierce our hearts.

Our life is changed; their coming our beginning.

-Edwin Muir

The science on gut microbiota and intestinal gas: Everything you wanted to know but didn’t want to ask

/in Consumer Blog, ISAPP Science Blog /by KC

By Kristina Campbell, science and medical writer

Even on the days when you don’t eat a large meal of Boston baked beans, the inside of your intestines is a gas-generating factory. This serves a valuable purpose for the body when everything is working as it should, with gases being produced and eliminated through a complex set of physiological processes. But sometimes gas becomes a problem—and this is when it’s valuable to know not only what contributes to intestinal gas symptoms, but also how dietary adjustments can alleviate some of the problems.

Dr. Fernando Azpiroz, Chief of Gastrointestinal Research at the Vall d’Hebron Research Institute and Professor of Medicine, Autonomous University of Barcelona (Spain), is an expert in both the pathophysiology of the gas produced in the digestive tract and the clinical problems related to intestinal gas. Dr. Azpiroz is the author of a chapter on intestinal gas in the well-known textbook, Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, which is now in its 10th edition. And for more than 20 years he has been conducting research on digestive tract function, intestinal gas, and the contributions of the gut microbiota.

ISAPP caught up with Dr. Azpiroz to ask him about everything you wanted to know—where intestinal gas comes from, when it becomes a problem, and the latest research on the dietary changes that can reduce symptoms of intestinal gas while keeping the gut microbiota intact.

In different parts of the digestive tract, where does intestinal gas come from?

For the most part, the gas in the digestive system comes from metabolic activities of the colonic microbiota.

In addition, some air enters the stomach during swallowing. Most of this air is eliminated by eructation (i.e. burping), so there is a homeostasis. There is a small air chamber in the stomach of about 20 mLs, and this is pure atmospheric air, or CO2 after recent consumption of carbonated drinks.

In the small intestine, the neutralization of acids and alkali can theoretically produce large amounts of CO2. However, it’s more in theory than measured in experimental conditions.

Other gases originate from the metabolism of the gut microbiota. The residues of the diet that are not absorbed in the small bowel pass into the colon. These are the parts of the diets that we, as humans, cannot use. These pass into the colon, and in the colon serve as substrates for colonic microbiota. Gas is produced during this process of colonic fermentation.

What types of gases are produced in the digestive tract?

The composition of intestinal gas depends on where in the gut it is produced.

In the stomach, the gas is virtually all atmospheric air or CO2.

In the small bowel, theoretically it should be CO2, although the hard data are very scarce.

And in the colon, the largest component is likely hydrogen and CO2. But the data on that are very limited, and it is not known for sure that these theories are really true. The measurements of gas composition, in the colon or even in the gas eliminated per anus are still uncertain but so far the main concept is that most of the gas is hydrogen and CO2, and methane in subjects that have a methanogenic microbiota.

How does this gas normally get eliminated?

Throughout the GI tract, particularly the colon, about 80% of the gases produced are absorbed through the mucosa, pass into the blood, and are eliminated by breath. So only about 20-25% of the volume of gases produced, particularly in the colon, are eliminated per anus.

What influences the amount of gas produced?

The amount of gas produced in different subjects depends on two factors: one is the diet—the amount of residues (i.e. fiber) in the diet—and the second is the type of microbiota, which is very individual. It varies a lot from one subject to another.

How much intestinal gas is ‘too much’?

From the point of view of patients, of symptoms, what might be relevant is the volume of gases produced, and possibly the type of gases. One evolving idea is that some gases, which are produced in very small quantities, might serve as neurotransmitters, might play a role, but so far the information we have about the role of these gases is very limited so we cannot extrapolate that to clinical use.

Very recent data indicate that symptoms occur when the GI tract has a poor tolerance to its contents, and particularly to gas.

So what is the factor that makes gas produce symptoms? Well there are two factors. One is the amount of gas, and the other one is the tolerance of the subject.

In healthy subjects, it will typically take a large amount of gas to develop symptoms, if at all.

But even small amounts of gas in patients that have a hypersensitivity of the gut and poor tolerance to contents might contribute to their symptoms. This can be seen because, if we reduce the amount of flatulogenic substances in their diet, the symptoms reduce.

This is if we just take into consideration the volume of gas produced, but there is also another factor.

If we give a high flatulogenic diet or a high-residue diet, we know, because we have measured, that we increase the volume of gas produced into the colon. However, we also increase the amount of the fecal content in the colon. So it could be that these diets produce symptoms because they increase the amount of gas, but also because other non-gaseous components, the fecal content of the colon, also are poorly tolerated.

How can someone manipulate their diet to change the amount of intestinal gas that’s produced?

A ‘challenge’ diet, or a high flatulogenic diet in healthy subjects, makes them sick. They go from being symptom-free to having some symptoms, particularly flatulence and bloating.

In patients, the effect of the diet is more accentuated. If patients consume a diet with high residues they get very symptomatic, and if these patients will reduce residues in the diet, they see quite an improvement.

What are the options for dietary change when someone has IBS or wants to reduce gas symptoms?

One thing that has been shown recently is that the effect of a low-residue diet is similar regardless of the type of diet. In the past ten years or so there’s been a major trend with the use of low-FODMAP fermentable oligo-, di-, mono-saccharides and polyols diets.

However, the effect of these complex diets is not better than the effect of any sensible and simple low-residue diet. So if you reduce legumes, veggies from the diet, and fruits, you get a similar improvement.

The problem with low-residue diets, in particular the low-FODMAP diet, is that they introduce a restriction of the substrates for the feeding of the microbiota, and this is deleterious to the microbiota. The microbiota is impoverished.

The other limitation of low-residue diet is that the moment that the patient returns to a normal diet, the symptoms come back.

There is an alternative that has been shown in the past few years, which is to use some type of prebiotics that initially—because they are fermented—produce symptoms, but after a few days they induce an adaptation of the microbiota towards a microbiota that produces less gas with normal fermentation. And down the road, these prebiotics have a positive effect on symptoms in patients. As a matter of fact, the effect on symptoms is similar to a restrictive diet. The advantage of the prebiotics is that, after interruption, …the effect is sustained at least over a few weeks. And this is because it has been shown that prebiotics serve as substrates for microbiota and induce a proliferation of beneficial organisms.

There is also some preliminary evidence that some probiotics reduce the volume of gas production and reduce digestive symptoms in patients.

Is it a good idea to test your gut microbiota when you have IBS or gas symptoms?

There are different companies that claim that by analyzing microbiota they can diagnose some functional conditions, for instance IBS. The practical application of this technology has not been demonstrated. Usually they are expensive techniques and of no value.

It’s important to understand the real value of these methodologies and take the myth out of ‘wonder’ techniques that make a diagnosis from the microbiota and claim it explains everything.

Hopefully, this might be true in the future, but not right now. And actually many of the technologies that are used for this type of analysis are suboptimal.

 A previous blog post by Dr. Bob Hutkins on diet, gut microbiota, and intestinal gas is ISAPP’s most-read blog post of all time. Read it here.

The past decade of probiotics and prebiotics research: ISAPP board members share their perspectives.

/in ISAPP Science Blog, Consumer Blog /by KC

By ISAPP board members, compiled by Kristina Campbell

Scientific progress in the field of probiotics and prebiotics, as in any other field, often seems to occur one tiny step at a time. Yet over the course of several years, these tiny steps can add up to significant progress.

Current members of the ISAPP board of directors hold academic positions across North America, and Europe, representing some of the experts at the forefront of scientific innovation in probiotics and prebiotics. Their collective experience encompasses functional foods, fermentations, microbial ecology, microbial genetics, immunology, and clinical medicine, including pediatrics, family medicine and gastroenterology. As we enter into 2020 and a new decade, these board members have taken a moment to reflect on how far they and their colleagues have come over the past ten years, by answering the question: What changes have occurred in the domains of research, applications, and awareness about probiotics and prebiotics?

ISAPP board members, 2019 annual meeting

Available scientific methods and tools

The change that stood out the most to the ISAPP board members over the past decade was the rapid expansion of available scientific methods and tools – from gene sequencing technology to CRISPR-Cas to bioinformatic approaches. These exciting developments have enabled scientists to obtain more information, and to do it both quickly and economically. In the words of the board members:

“Advances in sequencing technology [have] revolutionized our ability to understand the gene repertoire of each individual probiotic strain (whole genome sequencing) and the interplay with the microbiome (metagenomics). This has been really energizing to the field, but has also meant that competence in bioinformatics has become an essential tool for probiotic and prebiotic scientists.”

“A decade ago, human studies on prebiotics would look at changes in the gut microbiota using fairly laborious procedures. Nowadays, the analysis is much more extensive and straightforward to do, and probably more accurate… The biggest change has been the capability to assess not only composition of the microbiota but also its functionality. So, today, the trials include metabonomics as well as assessments of health effects (through changes in particular symptoms and /or biomarkers such as blood lipids, microbial products, immune and inflammatory status). That way, we get a far better picture of what prebiotics can do.”

“In 2010 we only had DGGE to characterize the genome and were trying to figure out how to implement 16S amplicon sequencing. Now we are implementing shotgun & shallow shotgun sequencing for similar prices. In 2010, we did only work on 3-4 probiotic lactobacilli for molecular research, now we work on 400-500 lactobacilli. We do comparative genomics and functional analyses at much larger scale. And in 2010, we paid almost 10000 euro just to sequence one genome of lactobacilli, with limited analysis, now a few hundred euro for sequencing.”

Probiotics and prebiotics for microbiome modulation

Because of the rapid advancements in scientific tools and techniques during the past decade, as mentioned above, many more research groups are endeavoring to study the microbial communities that relate to probiotics and prebiotics. Gut microbiota are of great interest—not least because, among the strategies for microbiome modulation, probiotics and prebiotics are two of the leading candidates. Moreover, microbiome data can help researchers understand the context of probiotics and prebiotics in the gut and in different environments. In particular, many clinical trials of probiotics and prebiotics now include a microbiota-related measure. Novel species and strains for food use may be identified from gut microbiota studies, although safety and efficacy assessment will form challenges for regulatory bodies. Board members said:

“My collaborators and I initiated our first human clinical trials with prebiotics in 2008 and published several papers in 2010 and 2011. These early papers were among the first in which high throughput 16S DNA sequencing was used to assess how the human gut microbiota was affected by the prebiotic, GOS. Although this is now a routine method in the field, in 2008, having a Roche 454 pyrosequencer in the lab was very special, and we were astounded to be able to identify and measure abundances of the main members of the gut microbiota. Having these large data sets also led us to realize the importance of what was at the time the “new” field of bioinformatics that was critical in analyzing and reporting the data. This research showed that GOS was bifidogenic (with high specificity) in healthy adults, but was also subject-dependent. Thus, the results clearly showed there were prebiotic responders and non-responders. This remains an important area of research for my group.”

“The decade started with general excitement that ‘dysbiosis’ of the gut microbiota is involved in just about every human health problem, and has turned into re-remembering that correlation is not causation and microbiota patterns are often driven more by random factors or factors unrelated to disease than by microbiology.”

“It’s worth noting that in 2020, the well-controlled probiotic studies showing health benefits in humans are still more convincing and valuable than the studies showing any ‘beneficial’ effects on the human microbiota.”

“Over the past decade we have witnessed a tremendous explosion in our understanding of the microbiome and its interactions with us, its host. Progress in translating this knowledge into new treatments has been slower but glimmers of encouragement have appeared and we look forward to the next decade when interventions that modulate the microbiome to benefit our health will be based on a true understanding of how they act and will be selected to the maximal benefit of each individual.”

Probiotic mechanisms of action

Probiotic mechanisms of action are a perennial hot topic within the scientific community—and many had hoped that the new suite of scientific tools at scientists’ disposal would significantly advance this area of research during the past decade. But according to one ISAPP board member:

“In 2010 I would have confidently predicted that by 2020 we would have much more of a mechanistic understanding of probiotic mechanisms [and] the importance of strain effects… But this simply has not happened.  The field has become more biologically and computationally complex and many millions have been spent on research, but I still don’t think we can answer the fundamental question we faced in 2010, and in 2000, and in 1990 – what makes one a strain a probiotic, while another is not?”

But in the views of other board members:

“Through genomic and metabolomic studies we are identifying differences between strains that function at different sites and what properties are important for their probiotic function.”

“Identify[ing] the key effector molecules turned out to be more complex [than] we thought 10 years ago. It has become clear to me that probiotic mechanisms of action are per definition complex and multifactorial, because they are living microbes having thousands of molecules that all play a role. Yet, there is clearly an hierarchy of effector molecules.”

Probiotic and prebiotic applications

In general, microbiome studies of the past decade have led to a better appreciation of the ubiquity and complexity of microbial communities—not just those associated with different human body sites, but also those occupying every possible niche on Earth. ISAPP board members reflect:

“In 2010, I was mainly studying probiotics for the gut and vagina, now we have explored probiotics for the skin, respiratory tract, animals, plants, isolates from fermented vegetables that can boost vegan probiotic formulations etc., and other areas.”

“Two areas of research I am doing I’d never have imagined in 2010 are in honey bees and Chinook salmon and against environmental chemicals, administering probiotics.”

Public awareness of probiotics and prebiotics

Numerous studies and surveys show the general public has more awareness than ever of probiotics – and increasingly, of prebiotics too. Individuals receive their information through many different channels, both digital (e.g. blogs, websites) and non-digital (e.g. magazines, product packaging). The past decade also saw the creation of valuable evidence-based resources, such as the Clinical Guides available in the US and Canada, and resources from World Gastroenterology Organisation and from ESPGHAN (probiotics for pediatric acute gastroenteritis, pediatric nosocomial diarrhea, preterm infants, and pediatric AAD). These resources have been enabled by a critical mass of studies that have examined the efficacy of various probiotic strains for certain indications. One board member says:

“From a clinical perspective, the biggest change for us has been that the general public knows so much about probiotics; now we are doing a lot less educating of docs and patients about the concepts behind our probiotic studies.”

But there’s still work to be done:

“The term probiotic is now widely known, but still too often people are misinterpreting what it means, or generalizing the whole field instead of recognizing strain and product differences. We need to continue to educate and clarify to keep the messaging on track.”

“There is still lack of knowledge that not all probiotics are equal. The clinical effects and safety of any single probiotic or combination of probiotics should not be extrapolated to other probiotics. The same applies to prebiotics.”

“Choosing a probiotic continues to be a major hurdle for the consumer – for every probiotic strain that is well characterized, studied in detail in appropriate disease models, and shown to be effective in clinical trials there are hundreds that would fail to pass even the most basic tests of quality control. We must help the consumer to make informed choices.”

 

It seems that, while the past decade has been a fruitful time for probiotics and prebiotics research and public awareness, scientists still have a lot of work to do. In the 2020s they will use the tools available to them, and continue to develop new ones, to gain more detailed and multi-faceted information about probiotic strains and prebiotic compounds—and about the context in which they operate (for instance, the gut microbiome), to ultimately confer benefits on human health.

Probiotics, Prebiotics and Globobiotics!

/in Consumer Blog, featured, ISAPP Science Blog /by ISAPP

By Prof. Colin Hill, PhD, APC Microbiome Ireland, University College Cork, Ireland

Growing up I could not imagine what the world would look like in 2020, but I was convinced it would be amazing. The future was exciting, new planets and solar systems would be explored, diseases would be cured, and everyone would have sufficient food and shelter.  I sometimes think my generation may have been born at the most perfect time in human history (for someone brought up in a first world country at any rate).  We avoided the major world wars which our parents and grandparents endured, we had the benefits of cheap airfares so we could travel the world as tourists, not as armies. Oil was cheap and plentiful. Access to education was widely available. We benefited from antibiotics while they were still effective.  Gender inequalities and racism began to be addressed, even though there is still a long way to go. Computers became commonplace and the internet provided access to almost unlimited sources of information.

But here we are in 2020, and now things do not look so promising. Perhaps cynicism is a natural by-product of getting older, but now the future seems to be presented in apocalyptic terms. Climate change, antibiotic resistance, ageing populations, the paradoxes of increasing obesity and increasing hunger, exploding populations, depletion of natural resources and pollution of our oceans. Watching nature programmes hosted by the incomparable David Attenborough has changed from generating a sense of awe at the wonders of the natural world to a sense of despair as to what we are doing to it. Australia is literally on fire as I write this!  Can our planet survive the onslaught of the projected 10 billion humans by 2050 – each one hungry for a share of finite resources?  Is this really going to be the legacy from my generation to the next – a dystopian future without hope and optimism?

But it’s a New Year and a new decade, and I really want to be hopeful. I am encouraged by the fact that we are gradually beginning to come to grips with this new reality. The UN Sustainable Development Goals provide a roadmap guiding societies and individuals as to how to make a contribution. Attitudes are changing.  Too slowly for sure, but we do seem to be at a tipping point.

But what has this tirade have to do with prebiotics and probiotics, you may ask? Well, everything of course. One of the things that really gives me hope is our growing understanding of how humans are simply occupying space in a microbial world. If we squander our opportunity and destroy our planet in terms of human habitation, microbes will carry on for billions of years to come. We should remember that we can only live on Earth because all of the oxygen we breathe is the result of billions of years of microbial metabolism, that most of the carbon cycling on earth is due to microbes, and that every natural system on Earth depends on microbes. Of course we are also inhabited by a vast ecosystem of microbes (our microbiomes) that are required for our health and wellbeing, and we live in environments shaped by microbes. Understanding this will help us to live in harmony with our microbial world, rather than constantly forcing our poor planet to deliver our short term needs.

How can microbes help us to achieve sustainability and restore a healthy ecosystem? I believe that there are many opportunities. By 2050 I predict that we will be using microbes to restore productivity to land damaged by excessive use and pollution.  We will be using microbes to clean our oceans of plastic waste. We will improve food production without using chemicals, and we will have certainly reduced food waste (it is estimated that one third of all the food we produce on earth is lost to spoilage, much of it caused by microbes). We will have reduced methane emissions by manipulating the rumen microbiome in domesticated ruminants. We can look forward to a world where we can work with microbes to restore and replenish our atmosphere by unlocking the enormous potential of microbes to scavenge and store carbon. We will have reduced our reliance on antibiotics and will have found microbiome-friendly solutions to prevent and treat infection. We will have developed probiotics and prebiotics that will help us to address metabolic diseases, we will be using bacteriophage to sculpt microbiomes, while psychobiotics will be helping to prevent age related loss of brain function.

Given that the world is a microbial ecosystem, I propose that in the same way we can treat our human ecosystems with prebiotics and probiotics to improve or restore health, we can think in terms of developing microbial solutions to improve or restore planetary health. Because we haven’t had one in at least a month, I propose yet another new term; globobiotics. Globobiotics would be defined as “live microorganisms, microbial products or substrates selectively utilized by microorganisms, that are used in a manner that contributes to the sustainability of our planet”.

We’ve had the Stone Age, the Iron Age, the Oil Age, the Atomic Age and the Information Age, welcome to the Microbial Age!

ISAPP discussion group leads to new review paper providing a global perspective on the science of fermented foods and beverages

/in Consumer Blog, ISAPP Science Blog, News /by KC

By Kristina Campbell, MSc, Science & Medical Writer

Despite the huge variety of fermented foods that have originated in countries all over the world, there are relatively few published studies describing the microbiological similarities and differences between these very diverse foods and beverages. But in recent years, thanks to the availability of high throughput sequencing and other molecular technologies combined with new computational tools, analyses of the microbes that transform fresh substrates into fermented foods are becoming more frequent.

A group of researchers from North America, Europe, and Asia gathered at the International Scientific Association for Probiotics and Prebiotics (ISAPP) 2018 conference in Singapore to discuss the science of fermented foods. Their goal was to provide a global perspective on fermented foods to account for the many  cultural, technological, and microbiological differences between east and west. This expert panel discussion culminated in a new review paper, published in Comprehensive Reviews in Food Science and Food Safety, entitled Fermented foods in a global age: East meets West.

Prof. Robert Hutkins, the paper’s lead author, says the diversity of panelists in the discussion group was an important aspect of this work. “Although we were all connected by our shared interests in fermented foods, each panelist brought a particular expertise along with different cultural backgrounds to our discussions,” he says. “Thus, one of the important outcomes, as noted in the published review paper, was how greatly historical and cultural factors, apart from microbiology, influence the types of fermented foods and beverages consumed around the world.”

The review captures the current state of knowledge on the variety of microbes that create fermented foods: whether these are starter cultures or microbes already present in the surrounding environment (i.e. the ‘authochthonous’ or ‘indigenous’ microbiota). The paper identifies general region-specific differences in the preparation of fermented foods, and the contrast between traditional and modern production of fermented foods—including the trade-offs between local and larger-scale manufacturing.

The authors of the article also took on the painstaking work of cataloging dozens of fermented foods from all over the world, including fermented milk products, fermented cereal foods, fermented vegetable products, fermented legume foods, fermented root crop foods, fermented meat foods, fermented fish products, and alcoholic beverages.

The expert panel discussions held every year at the ISAPP annual meeting provide a much-anticipated opportunity for globally leading scientists to come together to discuss issues relevant to scientific innovation and the direction of the field. This paper is an example of a concrete outcome of one of these discussion groups.

For more on fermented foods, see this ISAPP infographic or this educational video.

Maintaining a family tradition: Bulgarian whole fermented cabbage

/in Consumer Blog, ISAPP Science Blog /by KC

By Mariya Petrova, PhD, Microbiome insights and Probiotics Consultancy, Karlovo, Bulgaria

Dr. Mariya Petrova with her father

November and December mark a wonderful time of the year when the cold weather makes you want to stay at home and enjoy homemade foods and drinks. However, the heavy food during the holidays makes all of us think about healthier alternatives and how to keep our gut microbiomes in check. That’s why it can be great idea to supplement your festive menu with fermented foods.

Cabbage ready to be fermented

Partly to have healthier food options at home and partly to engage in longstanding traditions, at this time of the year, millions of people in Eastern Europe roll up their sleeves, get out their knives, salt and large containers, and make fermented vegetables at home. While Western cultures are seeing fermented foods as a trendy health food option, Eastern Europeans have never forgotten how to preserve food by using natural fermentation. In my country of Bulgaria, fermented foods are simply a part of our life. Our most popular fermented foods include whole sour cabbage, pickles and pickled vegetables, yogurt, boza (a special fermented beverage), and fermented apple cider vinegar. We do not take shortcuts by pickling our vegetables with vinegar. Ours is a traditional fermentation process – add salt and then let the natural lactic acid bacteria perform their magic.

Although all of these products are interesting and delicious, the winter season brings to my mind my father’s whole cabbage fermentation. My father is busy with it every year from the beginning of November until mid-December. Whole sour cabbage is a fermented food popular not only in Bulgaria but in many of our neighboring countries such as Serbia, Macedonia, and Romania. Although similar to sauerkraut, Bulgarian whole fermented cabbage ferments the entire cabbage head, not separate cut or shredded leaves. Using whole cabbage requires both an extended period of fermentation time (around 30 to 40 days) and extra care in handling.

Preparing for fermentation

I have pictures etched in my mind of a busy local Saturday vegetable market where people would buy between 30-50 kilograms (sometimes even more) of cabbages for fermentation – depending on the size of their families. These come to life every time I hear “fermented foods” at a conference!

Cabbage and brine

But how do you ferment such a spectacular amount of cabbage? Well, first you need some rather large barrels, of course. Then you remove the outer leaves from the cabbage, core the cabbage heads, and stick them in the barrel. This is not unlike putting together a jigsaw puzzle. The cabbage heads have to be very dense without leaving to much space between them or the fermentation will not work well. The cabbage is then covered with a brine of around 2-4% salt. Finally, something heavy is placed on top of the cabbage. Many people place a heavy rock (clean of course), to keep the cabbage heads under the salty water and to allow them to ferment properly. Packing the cabbage densely and pressing it down is done to reduce oxygen to a minimum, creating an anaerobic environment for the fermentation. For better taste some people optionally add apple, quince, horseradish, and/or beetroot (which also makes the salty water more pink).

Finished fermented cabbage

Every day the salty water has to be inverted which is achieved by flushing it from the bottom of the barrel by using connected vessels and then adding it onto the top. Day-to-day shuffling of the salty water ensures a uniform distribution of microorganisms in the barrel so that all cabbage heads ferment. The best quality fermented cabbage is produced at 12-18°C temperature for around 30 days. This is why the fermentation

is done only in November – to maintain these low temperatures. Temperature from 7.5 to 18°C favors the growth and metabolism of Leuconostoc mesenteroides, while temperatures higher than 20°C favor the growth of Lactobacillus species. At higher temperatures the fermentation process takes shorter time (around 10 days), but the quality of the fermented cabbage is lower. Leuconostoc mesenteroides is essential to start the first fermentation that produces lactic acid, acetic acid, ethyl alcohol, carbon dioxide, and mannitol. All these acids, in combination with aromatic ester alcohol, contribute to the characteristic taste of high-quality sour cabbage.

Following Leuconostoc mesenteroides fermentation, Lactobacillus plantarum takes over lactic acid production, which gives a sour taste to the fermented cabbage. At the end of this Lactobacillus fermentation the cabbage is ready to enjoy as part of traditional Bulgarian cuisine. Like a special gift left by St. Nick, many people use the salted water in which the cabbage was fermenting as a drink, rich in lactic acid bacteria, and said to help digestive health.

Acknowledgment: I thank my father for showing me how to make the fermented cabbage and taking some pictures of the process this year!

Fermented foods on the holiday dinner table

Highlighting the importance of lactic acid bacteria: An interview with Prof. Seppo Salminen

/in Consumer Blog, ISAPP Science Blog /by KC

By Kristina Campbell, M.Sc., science & medical writer

 

In a 2009 book called What on Earth Evolved?, British author Christopher Lloyd takes on the task of ranking the top 100 species that have influenced the planet throughout its evolutionary history.

What comes in at number 5, just slightly more influential than Homo sapiens? Lactobacilli, a diverse group of lactic-acid-producing bacteria.

The influential status of these bacteria on a global scale comes as no surprise to Prof. Seppo Salminen, ISAPP president and Professor at University of Turku (Finland), who has spent most of his career studying these microbes. He is the co-editor of the best-selling textbook Lactic Acid Bacteria: Microbiological and Functional Aspects, the fifth edition of which was released earlier this year. Salminen says the scientific community has come a long way in its understanding of lactic acid bacteria (LAB)—and in particular, lactobacilli.

Seppo Salminen at ISAPP annual meeting 2019

“If you think about the history of humankind, earlier on, more than 60% of the food supply was fermented,” explains Salminen. “On a daily basis, humans would have consumed many, many lactic acid bacteria.”

Yet 30 years ago when Salminen and his colleagues published the first edition of the textbook on lactic acid bacteria, they were working against perceptions that bacteria were universally harmful. The science on using live microorganisms to achieve health benefits was still emerging.

“Most people in food technology, they had learned how to kill bacteria but not how to keep them alive,” he explains. “They didn’t yet know how to add them to different formulations in foods and what sort of carrier they need. At that time, the safety and efficacy of probiotics was not well understood.”

Around ten years later, scientists came together to develop a definition of probiotics on behalf of the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO)—in a report that formed the basis of ISAPP Consensus meeting and today’s international consensus definition: “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”.

With probiotics having been more precisely defined, the following years were a time of rapid scientific progress in the field. Lactobacilli became the stars of the show, as research emerged on the benefits of various strains and combinations of strains in food science and medicine.

Fast forward to today, when rapidly expanding gut microbiome research adds another dimension to what we know about these bacteria. While lactic acid bacteria are still primarily of interest for the health benefits they impart, scientists can now also study their interactions with other microorganisms in the intestinal microbiome. In some cases, this kind of research may help uncover new mechanisms of action.

After everything Salminen and his textbook co-editors (Vinderola, Ouwehand, and von Wright) have learned about lactic acid bacteria over the past few decades, Salminen says there are two main reasons for the perennial importance of the bugs. “One is their importance in food fermentation, extending the shelf life of foods, making a kind of food processing or ‘agricultural processing’ possible. To make sauerkraut shelf-stable for weeks, or to make yogurt or cheese.”

The second reason, he says, relates to their benefits for the host. “Lactic acid bacteria, especially lactobacilli, reinforce intestinal integrity. So they protect us against pathogens; and sometimes against toxins and heavy metals by binding them away.”

He continues, “The more we know, the more we understand that LAB are needed. There are very specific strains that are helpful in different conditions for animal feeds or for clinical nutrition for infants, for example.” He says the knowledge is expanding at such a rapid pace that it may only be a few more years before the textbook he co-edited will need another edition.

Salminen is currently one of the world’s most cited probiotic researchers, and has diverse ongoing research projects related to digestive health, eczema, early life, and nutrition economics—but lactic acid bacteria are the thread that weaves everything together.

“I’m proud to be working on the fifth most important factor in human evolution,” he says.

Those probiotics may actually be helping, not hurting

/in Consumer Blog, ISAPP Science Blog /by KC

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP, and Gregory B. Gloor PhD, Department of Biochemistry, Schulich School of Medicine and Dentistry, The University of Western Ontario, London

 

A recent Wall Street Journal essay posits that probiotics are harmful, but does so by misrepresenting probiotic and microbiome science in some important ways.

The focus of this essay was an anecdotal report showing that consuming probiotic products (the composition of which was not disclosed), as well as making other dietary modifications, was associated with lower fecal microbiota diversity. This equates, in the author’s mind, to an “unhealthier gut” and leads to the sensational article title “Those Probiotics May Actually Be Hurting Your ‘Gut Health’”.

How important is fecal microbiota diversity to gut health? There is no evidence in humans that increased gut microbiota diversity is causally linked to any better health outcome. In hunter-gatherer populations, the diversity of the gut microbiome cycles seasonally with diet, yet both the low and high diversity microbiomes are presumably equally ‘healthy’. Many different gut diseases are associated with microbiota compositions that differ from those from healthy subjects. But importantly, we don’t know if the different microbiota is the cause of or the result of the disease. So contrary to the author’s assertion, to speak of gut health is not to speak “really…about the gut microbiome”. Scientists don’t even know what a “healthy microbiome” looks like (see review here).

Perhaps more importantly, it is not at all surprising that consuming high numbers of a few probiotics would result in lower fecal microbial diversity. Probiotics typically survive intestinal transit and are observed in fecal samples when the microbiota is measured. A quirk of measuring the microbiome is that it is typically measured as relative abundance, and the thing about relative abundance is that as the number of one microbe goes up, others appear to decline. They don’t decline in absolute number, but their percentage of the total measured is reduced and hence our ability to detect them is also reduced. So, when you add probiotic microbes to your gut microbiota, and then measure the species present, the probiotic organisms appear at the expense of others. As illustrated in the figure, the probiotic species will appear to displace many rare species because the probiotic species comprise a high percentage of the total population. Although the other resident bacteria are all still there, they are more difficult to detect because they are now below the detection limit after probiotics were added to the community.

 

We are not aware of any evidence that probiotics will increase the diversity of fecal microbiota. In fact, based on the rationale above, we expect that probiotics may appear to decrease fecal microbiota diversity. Does that mean probiotics are harmful? No.

The author glosses over another weakness in his anecdotal report. He treats his fecal microbiota as if it is equivalent to his gut microbiota. Fecal samples represent a terminal microbial community with diminishing nutrients and many dead, but measurable, bacteria. This community is much different from what occurs farther upstream in the colon, and likely has little in common with small intestinal microbial communities. Granted, this is a weakness of much research on the gut microbiome, but discerning scientific reporting should call this what it is: fecal microbiota, not gut microbiome.

Are probiotics actually good for us? To answer this question, consult the literature that evaluates specific probiotics for the health outcome that interests you. Some good evidence exists for several clinical endpoints including antibiotic-associated diarrhea, reduced risk of C. difficile, treatment of colic in infants, reduced incidence in upper respiratory tract infections, and others (see review here).

We agree with one conclusion of the essay, that eating a diverse, whole-food, high-fiber diet likely promotes gut health. But there is nothing new about this recommendation and it seems hardly worth column space in the Wall Street Journal.

 

 

The small intestinal ‘mysteriome’: A potentially important but uncharted microbiome

/in Consumer Blog, ISAPP Science Blog /by KC

By Eamonn MM Quigley MD FRCP FACP MACG FRCPI, Lynda K and David M Underwood, Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Houston, Texas, USA

 

Over recent years, countless publications have documented the status of the microbiota of the gastrointestinal tract by examining fecal samples. While this approach does provide a “snapshot” or representation of what is going on in the gut, and especially in the colon, it is a crude measure of the complex interactions between micro-organisms in the gut, as well as between these same microorganisms and us (their hosts). Fecal samples comprise a terminal microbial ecosystem, characterized by depletion of readily fermentable substrates, with a concomitant change in microbial composition, even compared to those farther upstream in the colon. It is unlikely, for example, that studies using fecal samples provide a full picture of what happens when bacteria (or other microorganisms) “talk” to the lining of the gut (the mucosa) or interact with the immune system of the intestine. Even less likely is that they provide any insights into bacterial populations in the small intestine, where most of the digestion of food and absorption of nutrients takes place. The small intestine also possesses the most abundant immune tissue of the entire gastrointestinal tract.

Yet, details of which bacteria actually inhabit this long and important organ, the small intestine, are sketchy. This lack of knowledge has apparently not restricted much theorizing and speculation about the role of an overgrowth of colonic-type bacteria (referred to as small intestinal bacterial overgrowth – SIBO) in the small intestine in many symptoms, disorders, and diseases. According to one especially popular theory – the “leaky gut” hypothesis – the list of conditions is nearly endless. The “leaky gut” hypothesizes that dysbiosis in the small intestine (in other words SIBO) and a disruption of the gut barrier leads to “leakage” of bacteria and bacterial products into the circulation causing inflammation, allergy, and autoimmunity.

There are several leaps of faith involved in “leaky gut” including, of course, the definition and diagnosis of SIBO. Traditional methods of diagnosing SIBO (obtaining fluid samples directly from the upper small intestine or a variety of breath tests) are fraught with problems and, in essence, have precluded a universally accepted definition of SIBO.

Fundamental to this dilemma is the definition of the normal small intestinal microbiome – how can we diagnose abnormal when we do not know the limits of normality? I would contend that, while there are situations where it is undoubted (based on the clinical context and various laboratory and other findings) that SIBO is an issue, there are countless more instances where SIBO is over-diagnosed and incorrectly implicated as the cause of an individual’s symptoms. This is an important issue as it can lead to the inappropriate use of antibiotics – something we all wish to avoid.

There is some good news – clever techniques exist for obtaining uncontaminated fluid samples from the small intestine, a capsule technology that permits live sampling of intestinal gases (generated by bacteria) as it traverses the intestine and the application, at last, of high-throughput sequencing, metagenomics, metabolomics, and metatranscriptomics to small intestinal microbiota suggest that the accurate definition of the normal small intestinal microbiome is not far off. At that time, we can all agree on an accurate and clinically meaningful definition of SIBO.

 

Is probiotic colonization essential?

/in Consumer Blog, ISAPP Science Blog /by KC

By Prof. Maria Marco, PhD, Department of Food Science & Technology, University of California, Davis

It is increasingly appreciated by consumers, physicians, and researchers alike that the human digestive tract is colonized by trillions of bacteria and many of those bacterial colonists have important roles in promoting human health. Because of this association between the gut microbiota and health, it seems appropriate to suggest that probiotics consumed in foods, beverages, or dietary supplements should also colonize the human digestive tract. But do probiotics really colonize? What is meant by the term “colonization” in the first place? If probiotics don’t colonize, does that mean that they are ineffective? In that case, should we be searching for new probiotic strains that have colonization potential?

My answer to the first question is no – probiotics generally do not colonize the digestive tract or other sites on the human body. Before leaping to conclusions on what this means for probiotic efficacy, “colonization” as defined here means the permanent, or at least long-term (weeks, months, or years) establishment at a specific body site. Colonization can also result in engraftment with consequential changes to the gut microbiota composition and function. For colonization to occur, the probiotic should multiply and form a stably replicating population. This outcome is distinct from a more transient, short-term (a few days to a week or so) persistence of a probiotic. For transient probiotics, it has been shown in numerous ways that they are metabolically active in the intestine and might even grow and divide. However, they are not expected to replicate to high numbers or displace members of the native gut microbiota.

Although some studies have shown that digestive tracts of infants can be colonized by probiotics (weeks to months), the intestinal persistence times of probiotic strains in children and adults is generally much shorter, lasting only few days. This difference is likely due to the resident gut microbiota that develops during infancy and tends to remain relatively stable throughout adulthood. Even with perturbations caused by antibiotics or foodborne illness, the gut microbiome tends to be resilient to the long-term establishment of exogenous bacterial strains. In instances where probiotic colonization or long-term persistence was found, colonization potential has been attributed more permissive gut microbiomes specific to certain individuals. In either case, for colonization to occur, any introduced probiotic has to overcome the significant ecological constraints inherent to existing, stable ecosystems.

Photo by http://benvandenbroecke.be/ Copyright, ISAPP 2019.

This leads to the next question: Can probiotics confer health benefits even if they do not colonize? My answer is definitely yes! Human studies on probiotics with positive outcomes have not relied on intestinal colonization by those microbes to cause an effect. Instead of colonizing, probiotics can alter the digestive tract in other ways such as by producing metabolites that modulate the activity of the gut microbiota or stimulate the intestinal epithelium directly. These effects could happen even on short-time scales, ranging from minutes to hours.

Should we be searching for new probiotic strains that have greater colonization potential? By extension of what we know about the resident human gut microbiota, it is increasingly attractive to identify bacteria that colonize the human digestive tract in the same way. In some situations, colonization might be preferred or even essential to impacting health, such as by engrafting a microbe that performs critical metabolic functions in the gut (e.g. break down complex carbohydrates). However, colonization also comes with risks of unintended consequences and the loss of ability to control the dose, frequency, and duration of exposure to that particular microbe.

Just as most pharmaceutical drugs have a transient impact on the human body, why should we expect more from probiotics? Many medications need to be taken life-long in order manage chronic conditions. Single or even repeated doses of any medication are similarly not expected to cure disease. Therefore, we should not assume a priori that any observed variations in probiotic efficacy are due to a lack of colonization. To the contrary, the consumption of probiotics could be sufficient for a ripple effect in the intestine, subtly altering the responses of the gut microbiome and intestinal epithelium in ways that are amplified throughout the body. Instead of aiming for engraftment directly or hand-wringing due to a lack of colonization, understanding the precise molecular interactions and cause/effect consequences of probiotic introduction will lead to a path that ultimately determines whether colonization is needed or just a distraction.

Prebiotics do better than low FODMAPs diet

/in Consumer Blog, featured, ISAPP Science Blog /by ISAPP

By Francisco Guarner MD PhD, Consultant of Gastroenterology, Digestive System Research Unit, University Hospital Vall d’Hebron, Barcelona, Spain

Bloating and visible abdominal distention after meals is a frequent complaint of people suffering from irritable bowel syndrome, but even generally healthy people sometimes have these complaints. These symptoms are thought to be due to fermentation of food that escapes our digestive processes. Some sugars and oligosaccharides end up at the far end of our small bowel and cecum, where they become food for our resident microbes.

To manage this problem, medical organizations recommend antibiotics to suppress the microbial growth in our small intestine (known as small intestinal bacterial overgrowth or SIBO) or avoidance of foods that contain fermentable oligosaccharides, disaccharides, monosaccharides and polyols, called a low “FODMAP” diet. These approaches are generally successful in reducing symptoms, but do not provide permanent relief: symptoms typically return after the strategies are stopped.

Even worse, both approaches are known to disrupt the entire gut microbial ecosystem (not only at small bowel and cecum). Whereas a healthy microbial gut ecosystem has many different types of bacteria, antibiotics deplete them.  The low FODMAP diet deprives beneficial bacteria (such as Faecalibacterium, Roseburia, Bifidobacterium, Akkermansia, Lactobacillus and others) of the food they like to eat, and these species wane (see here).

Prof. Glenn Gibson, a founding father of prebiotic and synbiotic science, suggested that increasing ingestion of certain prebiotics could increase levels of bifidobacteria. These bifidobacteria in turn could prevent excessive gas production since they are not able to produce gas when fermenting sugars.  (Instead, bifidobacteria product short chain fatty acids, mainly lactate, which are subsequently converted to butyrate by other healthy types of bacteria, such as Faecalibacterium and Roseburia.)

Prof. Gibson’s hypothesis was tested in pilot studies where volunteers ingested a prebiotic known as galacto-oligosaccharide (Brand name: Bimuno). Healthy subjects were given 2.8 g/day of Bimuno for 3 weeks. At first, they had more gas: significantly higher number of daily anal gas evacuations than they had before taking the prebiotic (see here). The volume of gas evacuated after a test meal was also higher. However, after 3 weeks of taking the prebiotic, daily evacuations and volume of gas evacuated after the test meal returned to baseline. The microbe populations also started to recover. The relative abundance of healthy butyrate producers in fecal samples increased and correlated inversely with the volume of gas evacuated. This suggested that the prebiotic induced an adaptation of microbial metabolism, resulting in less gas.

Then researchers launched a second study, also in healthy volunteers, to look at how the metabolic activity of the microbiota changed after taking this prebiotic. They showed that adaptation to this prebiotic involves a shift in microbiota metabolism toward low-gas producing pathways (see here).

A third controlled study (randomized, parallel, double-blind), this time in patients with functional gastrointestinal disorders with flatulence, compared the effects of the prebiotic supplement (2.8 g/d Bimuno) plus a placebo diet (mediterranean-type diet) to a placebo supplement plus a diet low in FODMAPs. The study subjects were divided between these 2 diets, which they consumed for 4 weeks (see here). Both groups had statistically significant reductions in symptom scores during the 4-week intervention. Once subjects stopped taking the prebiotic, they still showed improved symptoms for 2 additional weeks (at this point, the study was completed). However, for subjects on the low-FODMAP diet, once the diet was stopped, symptoms reappeared. Very interestingly, these 2 diets had opposite effects on fecal microbiota composition. Bifidobacterium increased in the prebiotic group and decreased in the low-FODMAP group, whereas Bilophila wadsworthia (a sulfide producing species) decreased in the prebiotic group and increased in the low-FODMAP group.

The bottom line conclusion is that a diet including intermittent prebiotic administration might be an alternative to the low FODMAP diets that are currently recommended for people with functional gut symptoms, such as bloating and abdominal distention. Since low FOD MAP diets are low in fiber, the prebiotic option may provide a healthier dietary option.

 

  1. Halmos EP, Christophersen CT, Bird AR, Shepherd SJ, Gibson PR, Muir JG. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015;64(1):93–100.
  2. Mego M, Manichanh C, Accarino A, Campos D, Pozuelo M, Varela E, et al. Metabolic adaptation of colonic microbiota to galactooligosaccharides: a proof-of-concept-study. Aliment Pharmacol Ther. 2017;45(5):670–80.
  3. Mego M, Accarino A, Tzortzis G, Vulevic J, Gibson G, Guarner F, et al. Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904 galactooligosaccharide use in humans. Neurogastroenterol Motil. 2017;29(9):e13080.
  4. Huaman J-W, Mego M, Manichanh C, Cañellas N, Cañueto D, Segurola H, et al. Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut Disorders. Gastroenterology. 2018;155(4):1004-7.

 

Additional reading:

Halmos EP, Christophersen CT, Bird AR, Shepherd SJ, Gibson PR, Muir JG. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut. 2015;64(1):93–100.

Mego M, Manichanh C, Accarino A, Campos D, Pozuelo M, Varela E, et al. Metabolic adaptation of colonic microbiota to galactooligosaccharides: a proof-of-concept-study. Aliment Pharmacol Ther. 2017;45(5):670–80.

Mego M, Accarino A, Tzortzis G, Vulevic J, Gibson G, Guarner F, et al. Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904 galactooligosaccharide use in humans. Neurogastroenterol Motil. 2017;29(9):e13080.

Huaman J-W, Mego M, Manichanh C, Cañellas N, Cañueto D, Segurola H, et al. Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut Disorders. Gastroenterology. 2018;155(4):1004-7.

Halmos EP, Gibson PR. Controversies and reality of the FODMAP diet for patients with irritable bowel syndrome. J Gastroenterol Hepatol. 2019 Jul;34(7):1134-1142. doi: 10.1111/jgh.14650. Epub 2019 Apr 4.