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Can we use fermented foods to modulate the human immune system?

By Dr. Paul Gill PhD, Monash University

Fermented foods have grown in popularity in recent years, marketed for their purported health effects, including on the gut microbiome and immune system. Many of us have had a family member or friend recommend to us kombucha or sauerkraut based on a claim of curing their ailments. However, a reliable recommendation goes beyond anecdotal evidence and the science of how fermented foods confer any health benefits is often poorly understood. We often associate health effects of fermented foods with bacteria such as lactobacilli or Bifidobacterium, but what is lesser known is the role of microbial metabolites. These have sparked recent interest, particularly amongst researchers.

Many fermented foods naturally contain a mixture of live microorganisms and metabolites, such as phenolic compounds and short-chain fatty acids (SCFA). All of these components have the potential to impact host immunity, through two main mechanisms. Firstly, by directly interacting with local gut immune cells that have receptors for bacterial components such as lipopolysaccharide or peptidoglycan. Secondly, by modulating gut microbiota composition or function that will lead to indirect changes to host immunity. Together, these mechanisms are important for regulation of gut barrier integrity and immune homeostasis. Furthermore, bacterial metabolites such as SCFA are also absorbed by the portal vein and reach peripheral circulation, suggesting that they may also play a role in regulating systemic immune responses.

Although many of these findings are based upon observations from in vitro studies or pre-clinical models, several pilot studies in humans have also reported similar effects. A recent trial in a small cohort of healthy people found that consumption of an average of six servings of fermented foods per day for 10 weeks was associated with reduced serum inflammatory markers. Furthermore, consumption of a diet that included three servings of apple cider vinegar each day for three weeks, increased levels of plasma short-chain fatty acids and reduced subsets of circulating lymphocytes in a group of 20 healthy people. Taken together, these studies highlight the potential anti-inflammatory effects of fermented foods and postbiotics.

It remains a challenge to attribute consumption of fermented foods to alterations in host immunity, particularly due to the complex nature of these foods. This is particularly the case for traditional fermented food products that are not well characterised. After isolation and identification of individual metabolites within fermented foods, characterisation of how these compounds are absorbed and interact within the body is also necessary to determine how frequently they should be consumed to have meaningful effects on the immune system. Future studies need to be designed of sufficient duration, with a realistic dietary intervention and optimal timing of biological sampling is crucial to validate observations from exploratory trials. Finally, studies in patients with immune deficiencies will be needed to assess safety and potential therapeutic benefit. Alternatively, studies in healthy people during an immune challenge, such as during vaccination, are another desirable approach to investigate immune and therapeutic effects of fermented food consumption.

The scientific and medical communities, alongside the food industry, are continuing to improve our understanding of how fermented foods may benefit our health and immune system, including which components are responsible for any health benefits. Future studies are still needed to confirm if these may be of therapeutic benefit, and who may benefit the most from consuming these products. As our knowledge evolves, it is important that we continue to follow expert groups such as ISAPP to keep well informed and correctly communicate this information to patients and the public.

Are the microbes in fermented foods safe? A microbiologist helps demystify live microbes in foods for consumers

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 the Dairy Products Institute (CONICET-UNL), Santa Fe, Argentina.

Since very early in my career I was drawn to science communication. I feel that rather than just producing my own results, silently in my lab, I can extend the reach of the science by amplifying other people’s work. At least in the southern cone where budgets for research have been always limited, science communication is a way to be active in science.

Before the pandemic I used my Instagram account mostly to share personal moments with my circle of family and friends. But when the COVID-19 pandemic hit, I saw interest in fermented foods skyrocket. I started sharing tips about how to prepare fermented foods, telling the science behind them, separating myths from facts, making Instagram Live videos with fermentationists, nutritionists, pediatricians and gastroenterologists, and I turned my personal Instagram account into a public one with an outreach of more than 100,000 followers (@gvinde), from Mexico down to Argentina.

During the pandemic, people were largely homebound and concerned about staying healthy.  The idea of healthy food to keep a diverse gut microbiome that had the potential to enhance our gut and respiratory immune systems against coronavirus really resonated with people. I even had the chance to participate in several radio and TV programs discussing these topics as well as making yoghurt, kefir, kombucha, sauerkraut and sourdough bread at home. I saw that people had the time to devote part of their days at home to keep these communities of microbes “cooking” for them. But these activities revealed to me that more people than I realized did not know that we can eat microbes in a safe way and that they may actually be good for us.

In my encounters, I found much confusion about fermented dairy products. People believe that dairy products must be kept refrigerated, but at the same time they see ultrapasteurized milk, powdered milk or hard cheeses marketed at room temperature. People find it difficult to understand why pasteurized milk should go in the refrigerator but not unopened ultrapasteurized milk.

Some hesitancy around bacterial safety exists because Argentina leads the world in annual cases of Uremic Hemolitic Syndrome (UHS), a life-threatening condition for children, especially those under the age of 5 years, caused by shiga-toxin producing Escherichia coli. Almost 400 children get sick in Argentina every year due to UHS. Among other recommendations, pediatricians tell parents not to offer their children unpasteurized dairy products. This leads to the the most common question I receive on Instagram from parents worried about yoghurt safety: Is yoghurt pasteurized?  “No!” I emphasize. “Yoghurt is not pasteurized, but it is made out of pasteurized milk. In fact, yoghurt has viable bacteria.” And this is when the panic begins.

If yoghurt has live bacteria, then can’t any bacteria grow there, even the bacteria responsible for UHS? If I leave yoghurt outside the refrigerator or in my car too long, won’t this make it more likely that the UHS bacteria will grow?” This is where I try to use an army of arguments to communicate science in the simplest possible way, from more philosophical to more science-based facts.

The first thing I share is that fermentation was invented well before refrigerators. Fermentation was used by people to preserve foods, for periods well longer than the time it takes to take the yoghurt from the supermarket to make it home or than the time a yoghurt sits in the backpack of my child waiting for school lunchtime. I once posted that I ate a yoghurt that was left in my car for one whole day. That generated a lot of debate on social media!

Then I inform them that the fermentation process to make yoghurt causes the pH to drop well below values needed for pathogens to grow. That it is highly unlikely that a pathogen can enter a well-sealed yoghurt, and in the event that it would be possible, the acidic conditions would impair the pathogen from growing to a level that could be life-threating.

People not only worried about yoghurts bought in the supermarket, well-sealed and made under the strictest safety conditions in industry. In the pandemic many parents learned how to make yoghurt at home, and they wanted to know how safe it is. In these cases, I advised the following to assure their homemade yogurt was safe: use a yoghurt from the supermarket to launch your own fermentation, use pasteurized milk, use good quality water to wash your kitchen devices, and wash your hands properly. In addition you can use a domestic pHmeter or pH indicators to make sure pH dropped below 4.5. In a successful fermentation – after about 1 gallon sitting 8-12 hours at a warm temperature – the fluid milk will transform into a gel. If not, you should discard it.

If these arguments are not enough, then I draw their attention to the well-respected product milk kefir. At least in this region, kefir is surrounded by a halo of “something that is good, no matter what”. People are familiar with the process of fermenting milk kefir at room temperature for a full day. So I make this comparison: commercial yoghurt is fermented for 6 hours, then it is refrigerated and taken to the supermarket. If you are OK letting milk kefir ferment for a whole day, shouldn’t yogurt sitting without refrigeration for a few more hours be harmless enough? It likely would only get more acidic because bacteria will resume fermentation. This fermented food would not become a life-threatening food in just a couple of hours. If milk kefir does not in 24 hours, why should yoghurt?

To further argue, I comment that kombucha is fermented at room temperature for 10 days, sauerkraut for 2 weeks and kimchi for several months. And they are all consumed with their microbes alive. They key is that the microbes that flourish make the environment inhospitable to pathogens.

Still I feel that there is a lot of uncertainty among consumers about the safety of fermented foods and this is may be an obstacle to making them more popular. Scientists must meet the challenge to communicate to lay audiences about how to make fermented foods safely at home and how to store them so they are safe. Nothing is ever 100% safe, but the small risks associated with fermented foods are greatly outweighed by the enjoyment of making and consuming fermented foods.

 

Additional reading:

Suggestions for Making Safe Fermented Foods at Home

2022 TEDx talk

2021 Teaching how to make kefir on TV during the pandemic

2019 participation in Argentina’s most famous TV show, featuring the same host for more than 50 years non-stop

Food of the future: Fermented and sustainable

By Dr. Mary Ellen Sanders, ISAPP Executive Science Officer

An exciting research initiative at the crossroads of fermented foods and sustainable diets is underway. Funded by the EU and Switzerland, and coordinated by KU Leuven in Belgium, HealthFerm is a 4-year, 13.1 MM € project involving 23 partners from 10 countries. Prof. Christophe Courtin, KU Leuven, serves as the overall project coordinator.

HealthFerm seeks to understand how to transition toward more sustainable, healthy diets through leveraging fermented foods and technologies. Its overall aim is to understand the interaction between food fermentation microbiomes, fermented plant-based foods, the human gut microbiome and human health. Many information gaps will be addressed by the project, which is organized around six work projects that are designed to integrate basic research, intervention studies, fermentation technology, consumer behavior and communication strategies.

Scientific perspectives on fermented food is at the heart of HealthFerm. Fermented foods were defined in an ISAPP consensus paper as ‘foods made through desired microbial growth and enzymatic conversions of food components’. Predating ancient Egyptian society, fermented foods and beverages are thought to have originated over 8000 years ago, and today over 5000 varieties are enjoyed around the globe, contributing substantially to human nutrition. Fermented foods have many advantages over the raw materials from which they are made, including improved sensory characteristics, safety and stability as well as potential health benefits. How the live microbial components of fermented foods may drive the health benefits of fermented foods is an active area of research.

Prof. Courtin shares some of his thoughts about HealthFerm.

Why focus on fermentation as a means of attaining more sustainable diets?

Courtin: When considering a sustainable diet, we automatically look at replacing part of our animal-based foods with plant-based foods. But plant biomass is often less functional and more recalcitrant than animal-based materials. Look for example at the whipping behavior of egg proteins or the availability of iron. Getting more out of plant fiber through fermentation is also a point of attention. In short, we believe that fermentation can help us functionalize plant materials and make it more nutritious.

 

Fermented foods have been around a long time. Why do you think now is the time to leverage their benefits?

Courtin: Societies are increasingly interested in fermented foods for a large number of reasons. We want to leverage that. From a scientific point of view, state-of-the-art omics-technologies coupled with bioinformatics allow us to look in depth into food microbiomes better than ever before and use them in a targeted way to functionalize plant materials. In addition, they also allow performing human intervention trials and doing relevant analyses to understand if and how fermented foods can improve human health, focusing on the gut microbiome and cardiometabolic health.

 

Looking ahead, what is your greatest hope for the project?

Courtin: I hope we can come to a rational design of new fermentation processes and products for the crops we target (faba bean, yellow pea, wheat, oats), using microbial resources we mobilize in collaboration with citizens and companies through community science projects. I also hope we get clear results and mechanistic insights from the intervention trials on the effects of consuming fermented foods and diets.

 

ISAPP is represented on the HealthFerm Stakeholder Board, which convened its first meeting January 20, 2023.

 

Episode 9: An evolutionary perspective on fermented foods

The Science, Microbes & Health Podcast 

This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

An evolutionary perspective on fermented foods, with Assoc. Prof. Katie Amato

Episode summary:

In this episode, the ISAPP hosts talk about fermented foods and non-human primates with Katie Amato of Northwestern University, USA. Amato describes what she has learned from studying the gut microbiota of non-human primates and how it relates to our understanding of human and gut microbial co-evolution over time. She also talks about non-human primate behaviors around fermented foods and what they might tell us about the need for human fermented food consumption.

Key topics from this episode:

  • A list of species categorized as non-human primates.
  • Changes in the gut microbiota of primates depend on habitats and available food across different seasons.
  • Primates in captivity have a different gut microbiota from wild ones – for example, animals kept in the zoo have a lower gut microbiota diversity.
  • Fermentation as a process to improve access to nutritional components of food; knowledge about primates’ use of fermentation and their gut microbes can tell us something about early human evolution.
  • Primates may derive benefits from using fermented foods. Consumption of fermented foods (overripe fruits) by primates is linked to certain habitats and climate factors; some non-human primates appear to intentionally leave fruits to ferment before returning to consume them.
  • There are benefits to translating the knowledge obtained from studying gut microbiota of primates to humans. 

 

Episode abbreviations and links:

Dissertation study: The Gut Microbiota Appears to Compensate for Seasonal Diet Variation in the Wild Black Howler Monkey (Alouatta pigra)

Study: Fermented food consumption in wild nonhuman primates and its ecological drivers

Mentors mentioned: Kathy Cottingham, Matt Ayres, David Peart, John Gilbert, Mark McPeek, Craig Layne, Rob McClung.
Steve Ross, Alejandro Estrada, Paul Garber, Angela Kent, Rod Mackie, Steve Leigh, Rob Knight.

Additional resources:

Research on the microbiome and health benefits of fermented foods – a 40 year perspective. ISAPP blog
New ISAPP-led paper calls for investigation of evidence for links between live dietary microbes and health. ISAPP blog

 

About Assoc. Prof. Katie Amato:

Dr. Amato is a biological anthropologist at Northwestern University studying the influence of gut microbes on host ecology and evolution. Her research examines how changes in the gut microbiota impact host nutrition, energetics, and health. She uses non-human primates as models for studying host-gut microbe interactions in selective environments and for providing comparative insight into the evolution of the human gut microbiota. Her main foci are understanding how the gut microbiome may buffer hosts during periods of nutritional stress and how the gut microbiome programs normal inter-specific differences in host metabolism. Dr. Amato is the President of the Midwest Primate Interest Group, an Associate Editor at Microbiome, an Editorial Board member at Folia Primatologica, and a Fellow for the Canadian Institute of Advanced Research’s ‘Humans and the Microbiome’ Program.

Episode 3: The science of fermented foods, part 2

The Science, Microbes & Health Podcast 

This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

The science of fermented foods, part 2, with Prof. Bob Hutkins

Episode summary:

Before listening to this episode, it’s recommended that you check out episode #1, The science of fermented foods, Part 1. In this episode, the hosts continue their discussion of fermented foods with Prof. Bob Hutkins, University of Nebraska – Lincoln. Prof. Hutkins elaborates on how the microbes associated with fermented foods may confer health benefits, as well as how food scientists choose strains for fermentation. He emphasizes how the live microbes in fermented foods differ from probiotics.

Key topics from this episode:

  • Why working in the field of fermented foods is exciting and rewarding
  • The challenges for scientists, especially when it comes to designing clinical studies with various fermented foods
  • The benefits of fermented foods – from being safe as well as nutritious, to the health benefits that live microbes present in the foods can provide
  • How microbes are selected for fermentation; companies focus on strain performance – i.e., good growth and survival to preserve the food and provide a desired flavor and texture
  • The activities of live microbes present in fermented foods, from initiating the fermentation process to benefiting human health
  • The differences between probiotics and live microbes in fermented foods
  • How live microbes in fermented foods might affect your gut microbiota and why some scientists believe that fermented foods are important for getting regular doses of live microbes

 

Episode links:

Microbiology and Technology of Fermented Foods, 2nd Ed., by Robert W. Hutkins
The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on fermented foods
The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic
Gut-microbiota-targeted diets modulate human immune status, study by Stanford researchers

 

Additional resources:

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics.
Postbiotics. ISAPP infographic
Fermented foods. ISAPP infographic
What are fermented foods? ISAPP video
Do fermented foods contain probiotics? ISAPP blog post
How are probiotic foods and fermented foods different? ISAPP infographic
Are fermented foods probiotics? Webinar by Mary Ellen Sanders, PhD

 

About Prof. Bob Hutkins:

Bob Hutkins is the Khem Shahani Professor of Food Microbiology at the University of Nebraska. He received his Ph.D. from the University of Minnesota and was a postdoctoral fellow at Boston University School of Medicine. Prior to joining the University of Nebraska, he was a research scientist at Sanofi Bio Ingredients.

The Hutkins Lab studies bacteria important in human health and in fermented foods. His group is particularly interested in understanding factors affecting persistence and colonization of probiotic bacteria in the gastrointestinal tract and how prebiotics shift the intestinal microbiota and metabolic activities. The lab also conducts clinical studies using combinations of pro- and prebiotics (synbiotics) to enhance health outcomes. More recently we have developed metagenome-based models that can be used in personalized nutrition.

Professor Hutkins has published widely on probiotics, prebiotics, and fermented foods and is the author of the recently published 2nd edition of Microbiology and Technology of Fermented Foods.

Episode 1: The science of fermented foods, part 1

The Science, Microbes & Health Podcast 

This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotic (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

The science of fermented foods, part 1, with Prof. Bob Hutkins

Episode summary:

The hosts discuss fermented foods with Prof. Bob Hutkins, University of Nebraska – Lincoln. Prof. Hutkins wrote a popular textbook on fermented foods and has had a 40-year career in fermentation science. He shares why he ended up in fermentation science, as well as how fermented foods are made and how important live microbes are for their health benefits.

Key topics from this episode:

  • What fermented foods are
  • The scientific consensus definition published by ISAPP
  • Fermentation processes and practices used in early times and still used today
  • The benefits and safety of fermented foods, as well as the difference between fermentation and food spoilage
  • The live microbes present in fermented foods, how many are present, and their potential health benefits
  • Why some fermented foods have live microbes and others do not; and how even when live microbes are absent due to heat treatment, for example, these products may still be classified as fermented 
  • The differences between fermented foods, probiotics, and probiotic fermented foods

 

Episode links:

Microbiology and Technology of Fermented Foods, 2nd Ed., by Robert W. Hutkins
The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on fermented foods
The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic
Synbiotics: Definitions, Characterization, and Assessment – ISAPP webinar featuring Prof. Bob Hutkins and Prof. Kelly Swanson

 

Additional resources:

Fermented foods. ISAPP infographic
What are fermented foods? ISAPP video
Do fermented foods contain probiotics? ISAPP blog post
How are probiotic foods and fermented foods different? ISAPP infographic
Are fermented foods probiotics? Webinar by Mary Ellen Sanders, PhD

 

About Prof. Bob Hutkins:

Bob Hutkins is the Khem Shahani Professor of Food Microbiology at the University of Nebraska. He received his Ph.D. from the University of Minnesota and was a postdoctoral fellow at Boston University School of Medicine. Prior to joining the University of Nebraska, he was a research scientist at Sanofi Bio Ingredients.

The Hutkins Lab studies bacteria important in human health and in fermented foods. His group is particularly interested in understanding factors affecting persistence and colonization of probiotic bacteria in the gastrointestinal tract and how prebiotics shift the intestinal microbiota and metabolic activities. The lab also conducts clinical studies using combinations of pro- and prebiotics (synbiotics) to enhance health outcomes. More recently we have developed metagenome-based models that can be used in personalized nutrition.

Professor Hutkins has published widely on probiotics, prebiotics, and fermented foods and is the author of the recently published 2nd edition of Microbiology and Technology of Fermented Foods.

New ISAPP Webinar: Fermented Foods and Health — Continuing Education Credit Available for Dietitians

Dietitians – along with many other nutritional professionals – often receive questions about consuming fermented foods for digestive health. But how strong is the evidence that fermented foods can improve digestive health?

ISAPP is pleased to work with Today’s Dietitian to offer a free webinar in which Hannah Holscher, PhD, RD, and Jennifer Burton, MS, RD, LDN will discuss the foundational elements of fermented foods, the role of microbes in fermentation, how they differ from probiotics and prebiotics, and how to incorporate fermented foods into client diets in an evidence-based manner. Participants will come away with a grasp of the scientific evidence that supports fermented food consumption. This activity is accredited by the Academy of Nutrition and Dietetics Commission on Dietetic Registration (CDR) for 1.0 CPEUs for dietitians.

The one-hour virtual event, titled “Fermented Foods and Health — Does Today’s Science Support Yesterday’s Tradition?”, was held April 20th, 2022, at 2:00 pm Eastern Time.

See the webinar recording here.

ISAPP and Today’s Dietitian also collaborated on a self-study activity titled “Evidence-based use of probiotics, prebiotics and fermented foods for digestive health”. This free activity, which provides more detail on the topic that the 1-hour webinar above, was approved by CDR to offer 2.0 CPEUs for dietitians and is available here through November 2023.

Bacterial genes lead researchers to discover a new way that lactic acid bacteria can make energy and thrive in their environments

Lactic acid bacteria are an important group of bacteria associated with the human microbiome. Notably, they are also responsible for creating fermented foods such as sauerkraut, yogurt, and kefir. In the past two decades, culture-independent techniques have allowed scientists to sequence the genomes of these bacteria and discover more about their capabilities.

Researchers studying a type of lactic acid bacteria called Lactiplantibacillus plantarum found something unexpected: they contained genes for making energy in a way that had not been previously documented. Generally, living organisms obtain energy from their surroundings either by fermentation or respiration. L. plantarum have long been understood to obtain energy using fermentation, but the new genetic analysis found they had additional genes that were suited to respiration. Could they be using both fermentation and respiration?

ISAPP board member Prof. Maria Marco is a leading expert on lactic acid bacteria and their role in fermented foods and in human health. In her lab at University of California Davis, she decided to investigate why L. plantarum had genes equipping it for respiration. Her group recently published findings that show a new type of “hybrid” metabolism used by these lactobacilli.

Here is a Q&A with Prof. Marco about these exciting new findings.

What indicated to you that some of the genes in L. plantarum didn’t ‘belong’?

Organisms that use respiration normally require an external molecule that can accept electrons, such as oxygen. Interestingly, some microorganisms can also use solid electron acceptors located outside the cell, such as iron. This ability, called extracellular electron transfer, has been linked to proteins encoded by specific genes. L. plantarum had these genes, even though this species is known to use fermentation. We first learned about their potential function from Dr. Sam Light, now at the University of Chicago. Sam discovered a related pathway in the foodborne pathogen Listeria monocytogenes. Sam came across our research on L. plantarum because we previously published a paper showing that a couple of genes in this pathway are switched on in the mammalian digestive tract. We wondered what the proteins encoded by these genes were doing.

How did you set out to investigate the metabolism of these bacteria?

We investigated this hybrid metabolism in a variety of ways. Using genetic and biochemical approaches we studied the extent to which L. plantarum and other lactic acid bacteria are able to use terminal electron acceptors like iron. Our collaborators at Lawrence Berkeley National Lab and Rice University contributed vital expertise with their electrochemistry experiments, including making fermented kale juice in a bioelectrochemical reactor.

What did you find out?

We discovered a previously unknown method of energy metabolism in Lactiplantibacillus plantarum. This hybrid strategy blends features of respiration (a high NAD+/NADH ratio and use of a respiratory protein) with features of fermentation (use of endogenous electron acceptors and substrate-level phosphorylation).

We verified that this hybrid metabolism happens in different laboratory media and in kale juice fermentations. We also found that, in the complex nutritive environment of a kale juice fermentation, this hybrid metabolism increases the rate and extent of fermentation and increases acidification. Within the ecological context of the fermented food, this could give L. plantarum a fitness advantage in outcompeting other microorganisms. This could potentially be used to change the flavor and texture of fermented foods.

This discovery gives us a new understanding of the physiology and ecology of lactic acid bacteria.

Are there any indications about whether this energy-making strategy is shared by other lactic acid bacteria?

Some other fermentative lactic acid bacteria also contain the same genetic pathway. It is likely that we are just at the tip of the iceberg learning about the extent of this hybrid metabolism in lactobacilli and related bacteria.

Your finding means there is electron transfer during lactic acid bacteria metabolism. What does this add to previous knowledge about bacterially-produced ‘electricity’?

Certain soil and aquatic microbes have been the focus of research on bacterially-produced electricity. We found that by giving L. plantarum the right nutritive environment, it can produce current to the same level as some of those microbes. We believe there is potential to apply the findings from our studies to better inform food fermentation processes and to guide fermentations to generate new or improved products. Because strains of L. plantarum and related bacteria are also used as probiotics, this information may also be useful for understanding their molecular mechanisms of action in the human digestive tract.

How might this knowledge be applied in practice?

Our findings can lead to new technologies which use lactic acid bacteria to produce healthier and tastier fermented foods and beverages. Because this hybrid metabolism leads to efficient fermentation and a larger yield, it could also help minimize food waste. We plan to continue studying the diversity, expression, and regulation of this hybrid metabolism in the environments in which these bacteria are found.

Do fermented foods contain probiotics?

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

We frequently hear that “fermented foods are rich in beneficial probiotics.” But is this actually true? Do fermented foods contain probiotics?

The quick answer to this question is no – fermented foods are generally not sources of probiotics. Despite the popular assertion to the contrary, very few fermented foods contain microbes that fit the criteria to be called probiotic. But this fact does not mean that fermented foods are bad for you. To uphold the intent of the word probiotic and to explain how fermented foods actually are healthy, we need to find better ways to describe the benefits of fermented foods.

Probiotics are living microorganisms, that when administered in adequate amounts, confer a health benefit on the host (Hill et al 2014 Nat Rev Gastroenterol Hepatol). This current definition reflects minor updates to a definition offered by an expert consultation of scientists in 2001 convened by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization. Evident from the definition, a microbial strain is not a probiotic unless a health benefit has been found with its use. At a minimum, the strain should be proven to be beneficial in at least one randomized controlled trial (RCT). Probiotics must also be defined at the strain level through genome sequencing (a strain is a single genotype of a species).

Fermented foods, on the other hand, have no requirement to improve health. Fermented foods are foods and beverages made through desired microbial growth and enzymatic conversion of food components. This definition was recently formulated by an ISAPP consensus panel of scientific experts to affirm the common properties of all foods of this type and to differentiate foods that may look or taste similar but are not made using microbes (Marco et al 2021 Nat Rev Gastroenterol Hepatol). Fermented foods encompass an expansive variety of foods made from animal and plant sourced ingredients and produced from all types of microbial metabolism. The desired characteristics of these foods are frequently how they look, smell, and taste. There no expectation in this definition that fermented foods alter health in any way.

There is also no requirement for fermented foods contain living microbes at the time they are ingested. Foods such as bread, chocolate, and beer are fermented but then are baked, roasted, and/or filtered. This means those fermented foods cannot be probiotic.

Some fermented foods, such as kimchi and kombucha, are typically eaten with living microbes present. However, the microbes in those foods usually do not meet the criteria to be called probiotic. Whether the fermented food was made at home or purchased from the supermarket, studies investigating whether the microbes in those fermented foods are specifically responsible for a health benefit remain to be done. Those foods also do not contain microbes defined to the strain level, nor is the number of living microbes typically known. An exception to this is if specific strains previously shown to provide a health benefit in one or more RCT are intentionally used in the production of the food and remain viable at expected numbers over the shelf-life of that fermented food product. An example of this would be a commercial fermented yogurt that has an added probiotic strain remaining viable at the time of consumption, beyond the strains that carried out the fermentation.

Despite these distinctions between probiotics an fermented foods, the probiotics term has pervaded common lexicon to mean “beneficial microbes”. In contrast to pathogenic or harmful microbes, beneficial microbes are those that are understood to help rather than hurt bodily functions. However, just as we do not assume that all pathogens cause the same disease or result in the same severity of symptoms, we should also not expect that beneficial microbes all serve the same purpose. By analogy, automobiles are useful vehicles which help us to get from place to place. We do not expect that all automobiles perform like those used for Formula 1 racing. Microbes are needed to make fermented foods and may be beneficial for us, but we should not assume that those drive health benefits like established probiotic strains.

What are the consequences of calling fermented foods probiotic when they include undefined numbers of living microbes for which strain identities are not known? One can suppose that there is no harm in labeling or describing those products as “probiotic” or “containing probiotics”. However, by doing so, confusion and misunderstanding is created and too often, spread by journalists, nutritionists, scientists, and medical professionals. For example, news articles in reputable sources have written that foods like kefir, kimchi, sauerkraut made from beets or cabbage, pickles, cottage cheese, olives, bread and chocolate are rich in probiotics. As misuse perpetuates, what becomes of bona fide probiotics shown with rigorous study to benefit health, such as reducing the incidence and duration of diarrhea or respiratory infections? It becomes difficult to know which strains have scientific proof of benefit. Just as there are laws for standards of food identity, we should strive to do the same when describing microbes in fermented foods.

Avoiding the term probiotic when describing fermented foods should not stop us from espousing the myriad of positive attributes of those foods. Besides their favorable sensory qualities, fermented foods are frequently safer and better tolerated in the digestive tract than the foods they are made from. During the production of fermented foods, microbes remove or reduce toxins in the ingredients and produce bioactive compounds that persist long after the microbes that make them are gone.

Even though the living microbes in fermented foods may not rise to the standard of a probiotic, they may provide health benefits. We just don’t have the studies to prove that they do. With more study, we may find that viable microbes in fermented foods work similarly to probiotics in the digestive tract through shared mechanisms. This is already known for yogurts. Yogurt cultures share the ability to deliver lactase to the intestine, thereby improving tolerance of lactose by intolerant individuals. Clinical and epidemiological studies performed on fermented foods already suggest an association between them and different health benefits but as we recently explained (Marco et al 2021 J Nutrition), more work is needed in order to understand if and what benefits these microbes provide.

For now, we should simply continue enjoying the making and eating of fermented foods and reserve the term probiotics for those specific microbial strains which have been shown to improve our health. Marketers should resist labeling products as containing probiotics if their products do not meet the criteria for a probiotic. Indeed, the descriptor “live and active cultures” more accurately reflects the microbial composition of many fermented foods, and should be used until controlled human trials demonstrating health benefits are conducted.

 

Additional resources:

How are probiotic foods and fermented foods different? ISAPP infographic.

Fermented foods. ISAPP infographic.

What are fermented foods? ISAPP video.

Are fermented foods probiotics? Webinar by Mary Ellen Sanders, PhD.

 

ISAPP’s 2021 year in review

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

The upcoming year-end naturally leads us to reflect about what has transpired over the past 12 months. From my perspective working with ISAPP, I witnessed ISAPP board members and the broader ISAPP community working creatively and diligently to find solutions to scientific challenges in probiotics, prebiotics and related fields. Let’s look back together at some of the key developments of 2021.

ISAPP published outcomes from two consensus panels this year, one on fermented foods and one on postbiotics. The popularity of these articles astounds me, with 49K and 29K accesses respectively, as of this writing. I think this reflects recognition on the part of the scientific community of the value – for all stakeholders – of concise, well-considered scientific definitions of terms that we deal with on a daily basis. If we can all agree on what we mean when we use a term, confusion is abated and progress is facilitated. The postbiotics definition was greeted with some resistance, however, and it will remain to be seen how this is resolved. But I think ISAPP’s response about this objection makes it clear that productive definitions are difficult to generate. Even if the field ultimately embraces another definition, it is heartening to engage in scientific debate about ideas and try to find alignment.

Keeping with the idea of postbiotics, a noteworthy development this year was the opinion from the European Food Safety Authority that the postbiotic made from heat-treated Akkermansia muciniphila is safe for use as a novel food in the EU. Undoubtedly, this development is a bellwether for likely future developments in this emerging area as some technological advantages to postbiotics will make these substances an attractive alternative to probiotics IF the scientific evidence for health benefits becomes available.

Recognizing the existing need for translational information for clinicians, ISAPP developed a continuing education course for dietitians. Published in March, it has currently reached close to 6000 dietitians. This course focused on probiotics, prebiotics and fermented foods: what they and how they might be applied in dietetic practice. It is a freely available, self-study course and completion provides two continuing education credits for dietitians.

On a sad note, in March of this year, ISAPP suffered the loss of Prof. Todd Klaenhammer. Todd was a founding ISAPP board member, and directed many of our activities over the course of his 18-year term on the board. He was also my dear friend and major advisor for my graduate degrees at NC State many years ago.  As one former collaborator put it, “I was not prepared to finish enjoying his friendship and mentorship.” See here for a tribute to Prof. Klaenhammer on the ISAPP blog: In Memoriam: Todd Klaenhammer.

So where will 2022 lead ISAPP? The organization has now published five consensus definitions: probiotics, prebiotics, synbiotics, postbiotics and fermented foods – extending its purview beyond where it started, with probiotics and prebiotics. Through the year ahead, ISAPP is committed to providing science-based information on the whole ‘biotics’ family of substances as well as fermented foods. Our Students and Fellows Association is growing, supported by the opportunity for young scientists to compete for the Glenn Gibson Early Career Researcher Prize. We continue to see our industry membership expand. Through our new Instagram account and other online platforms, our overall community is increasing. The ISAPP board of directors continues to evolve as well, with several long-term members leaving the board to make room for younger leaders in the field who will direct the future of the organization. This applies to me as well, as I have made the difficult decision to depart ISAPP in June of 2023. Thus, hiring a new executive director/executive science officer is an important priority for ISAPP in 2022. My 20 years with ISAPP have seen the organization evolve tremendously, through the hard work of incredible board members as well as many external contributors. We will strive to make 2022 – our 20th anniversary – ISAPP’s best year yet.

Research on the microbiome and health benefits of fermented foods – a 40 year perspective

By Prof. Bob Hutkins, PhD, University of Nebraska Lincoln, USA

Many ISAPPers remember when fermented foods attracted hardly any serious attention from scientists outside the field. Certainly, most clinicians and health professionals gave little notice to fermented foods. In the decades before there were artisan bakeries and microbreweries proliferating on Main Street USA, even consumers did not seem very interested in fermented foods.

When I began my graduate program at the University of Minnesota in 1980, I was very interested in microbiology, but I did not know a lot about fermented foods. Accordingly, I was offered two possible research projects. One involved growing flasks of Staphylococcus aureus, concentrating the enterotoxins, feeding that material to lab animals, and then waiting for the emetic response.

My other option was to study how the yogurt bacterium, Streptococcus thermophilus, metabolized lactose in milk. This was the easiest career choice ever, and the rest, as they say, is history.

Indeed, that lab at Minnesota was one of only a handful in North America that conducted research on the physiology, ecology, and genetics of microbes important in fermented foods. Of the few labs in North America delving into fermented foods, most emphasized dairy fermentations, although some studied vegetable, meat, beer, wine, and bread fermentations. Globally, labs in Europe, Japan, Korea, Australia, and New Zealand were more engaged in fermented foods research than we were in North America, but overall, the field did not draw high numbers of interested researchers or students.

That’s not to say there weren’t exciting and important research discoveries occurring. Most research at that time was focused on the relevant functional properties of the microbes. This included carbohydrate and protein metabolism, flavor and texture development, tolerance to acid and salt, bacteriocin production, and bacteriophage resistance. Despite their importance, even fewer labs studied yeasts and molds, and the focus was on lactic acid bacteria.

Other researchers were more interested in the health benefits of fermented foods. Again, yogurt and other cultured dairy foods attracted the most interest. According to PubMed, there were about 70 randomized clinical trials (RCTs) with yogurt as the intervention between 1981 and 2001. Over the next 20 years, there were more than 400 yogurt RCTs.

Fast forward a generation or two to 2021, and now fermented foods and beverages are all the rage. Certainly, having the molecular tools to sequence genomes and interrogate entire microbiomes of these foods has contributed to this new-found interest. Scanning the recent literature, there are dozens of published papers on microbiomes (and metabolomes) of dozens of fermented foods, including kombucha (and their associated symbiotic cultures of bacteria and yeast, known as SCOBYs), kefir, kimchi, beer (and barrels), cheese (and cheese rinds), wine, vinegar, miso and soy sauce, and dry fermented sausage.

It’s not just fermentation researchers who are interested in fermented foods. For ecologists and systems biologists, fermented foods serve as model systems to understand succession and community dynamics and how different groups of bacteria, yeast, and mold compete for resources.

Moreover, consumers can benefit when companies that manufacture fermented foods take advantage of these tools. The data obtained from fermented food microbiota analyses can help to correlate microbiome composition to quality attributes or identify potential sources of contamination.

Importantly, it is also now possible to screen microbiomes of fermented foods for gene clusters that encode potential health traits. Indeed, in addition to microbiome analyses of fermented foods, assessing their health benefits is now driving much of the research wave.

As mentioned above, more than 400 yogurt RCTs were published in the past two decades, but alas, there were far fewer RCTs reported for other fermented foods. This situation, however, is already changing. The widely reported fiber and fermented foods clinical trial led by Stanford researchers was published in Cell earlier this year and showed both microbiome and immune effects. Other RCTs are now in various stages, according to clinicaltrials.gov.

Twenty years ago, when ISAPP was formed, I suspect few of us would have imagined that the science of fermented foods would be an ISAPP priority. If you need proof that it is, look no further than the 2021 consensus paper on fermented foods. It remains one of the most highly viewed papers published by Nature Reviews Gastroenterology and Hepatology.

Further evidence of the broad interest in fermented foods was the recently held inaugural meeting of The Fermentation Association. Participants included members of the fermented foods industry, culture suppliers, nutritionists, chefs, food writers, journalists, retailers, scientists and researchers.

Several ISAPP board members also presented seminars, including this one who remains very happy to have made a career of studying fermented foods rather than the emetic response of microbial toxins.

Hands holding mobile phone

Virtual events continue to fill gaps as in-person meetings are being planned

Prof. Bob Hutkins, PhD, University of Nebraska – Lincoln, USA

For scientists, annual meetings provide coveted opportunities to hear about the latest scientific advances from expert researchers, and they are where students and trainees get to present their research, often for the first time. Of course, meeting and socializing with colleagues, both new and old, during breaks and evening sessions is also an important part of these conferences.

Yet over the past two years, most occasions to meet face-to-face were canceled. Virtual meetings became the new normal and, even though a poor substitute for in-person gatherings, provided opportunities to connect and share emerging science. As we anticipate being together again in person – hopefully for 2022 meetings – take note of three upcoming conferences to fill the gap. Each of these feature meetings are related to the gut microbiome, diet, and health.

(1) In October, the Agriculture and Health Summit: Cultivating Gut Health at the Crossroads of Food & Medicine is a FREE three-day virtual conference that brings together a unique combination of researchers, industry leaders and thought leaders from the biomedical and agricultural sectors for important conversations about the future of human health. The event will provide a rare opportunity for individuals with diverse areas of expertise to discuss opportunities and challenges in creating ‘foods for health’ through the gut microbiome, working toward solutions in nutrition and medicine. More information can be found here. Among the presenters are ISAPP Executive Science Officer, Mary Ellen Sanders, and board members, Dan Merenstein and Bob Hutkins.

 

(2) Then in November, a Nature-sponsored online conference called Reshaping the Microbiome through Nutrition will be held. According to the website, “this conference will bring together researchers working on the microbiome and nutrition to discuss how our microbiota use and transform dietary components, and how these nutrients and their products influence host health throughout life, including effects on development and infectious and chronic diseases. A central theme of the meeting will be how diet and dietary supplements could be harnessed to manipulate the microbiome with the aim of maintaining health and treating disease”More information is found here.

(3) Another meeting in November is organized across ten centers/institutes at the NIH and the Office of Dietary Supplements and the Office of Nutrition Research. This two-day conference November 5 and 8, titled Precision Probiotic Therapies—Challenges and Opportunities, features a Keynote address by Prof. Jeff Gordon, from the Washington University School of Medicine. ISAPP president Prof. Dan Merenstein, Georgetown University School of Medicine, is also presenting. To register for this FREE meeting, see here.

 

In this current era, interest in how diet (including probiotics, prebiotics, and fermented foods) influences the microbiome and affects human and animal health has never been greater, as is evident by these and other similarly-themed conferences.

ISAPP is planning its next annual by-invitation meeting, to be held in person.

 

Follow up from ISAPP webinar – Probiotics, prebiotics, synbiotics, postbiotics and fermented foods: how to implement ISAPP consensus definitions

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

On the heels of the most recent ISAPP consensus paper – this one on postbiotics – ISAPP sponsored a webinar for industry members titled Probiotics, prebiotics, synbiotics, postbiotics and fermented foods: how to implement ISAPP consensus definitions. This webinar featured short presentations outlining definitions and key attributes of these five substances. Ample time remained for the 10 ISAPP board members to field questions from attendees.

When considering the definitions, it’s important to remember that the definition is a starting point – not all criteria can be included. Using the probiotic definition as an example, Prof. Colin Hill noted that the definition is only 15 words – Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. This is a useful definition, stipulating the core characteristics of a probiotic. However, important criteria such as safety and identity are not specified in the definition yet are clearly delineated in the full paper on probiotics.

Several interesting topics emerged from this discussion, which will be explored in future blog posts. These include:

  • What is meant by host health? Microbe mediated benefits are numerous. But not all benefits are a benefit to host health. Benefits for user appearance, pets and potentially livestock may be measurable, economically important and desirable, but may not encompass ‘host health’.
  • What types of endpoints are appropriate for studies to meet the requirement of a health benefit? Endpoints that indicate improved health (such as symptom alleviation, reduced incidence of infections or quality of life measures) are targeted. Some physiological measures that may be linked to health (such as increased fecal short chain fatty acids or changes in microbiota composition) may not be sufficient.
  • What are the regulatory implications from these definitions? As suggested by the National Law Review article on the ISAPP consensus definitions, attorneys are interested in the scientific positions on how these terms are defined and characterized. Further, some regulatory actions – such as by Codex Alimentarius in defining probiotics – are underway. ISAPP is open to suggestions about the best way to communicate these definitions to regulators.
  • Is any follow-up by ISAPP to these papers anticipated in order to clarify criteria and provide simple guidance to their implementation?

Simple guidance to these substances can be found in the infographics: probiotics, probiotic criteria, prebiotics, fermented foodshow are probiotic foods and fermented foods different, synbiotics, and postbiotics. As mentioned above, watch for blog updates on implementation of the definitions for different stakeholder groups.

The recording of this webinar is available here under password protection for ISAPP industry members only.

Related information:

Consensus panel papers, all published in Nature Reviews Gastroenterology and Hepatology:

A roundup of the ISAPP consensus definitions: probiotics, prebiotics, synbiotics, postbiotics and fermented foods

 

 

 

 

A roundup of the ISAPP consensus definitions: probiotics, prebiotics, synbiotics, postbiotics and fermented foods

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

ISAPP has long recognized the importance of precise definitions of the ‘biotic’ family of terms. As a scientific organization working to advance global knowledge about probiotics, prebiotics, synbiotics, postbiotics and fermented foods, we believe carrying out rigorous scientific studies—and comparing one result to another—is more difficult if we do not start with a clear definition of what we are studying.

Over the past 8 years, ISAPP has endeavored to bring clarity to these definitions for scientists and other stakeholders. ISAPP board members have met with other top experts representing multiple perspectives and specialties in the field to develop precise, useful and appropriate definitions of the terms probiotics, prebiotics, synbiotics, postbiotics and fermented foods. The definitions of these first four terms have all entailed the requirement that the substance be shown to confer a health benefit in the target host. Fermented foods have multitudes of sensorial, nutritional and technological benefits, which drive their utility. A health benefit is not required.

The problem with health benefits

The definitions provide significant advantages for the scientific community in terms of clarity but complexity arises when the same definitions are accepted by regulatory agencies. This requirement for a health benefit as part of the probiotic definition has been rigorously implemented in the European Union. Currently, with the exception of a few member states, the term probiotic is prohibited. The logic is that since a health benefit is inherent to the term probiotic and since there are no approved health claims for probiotics in the EU*, the term ‘probiotic’ is seen to be acting as a proxy for a health claim. This has frustrated probiotic product companies who believe they have met the scientific criteria for probiotics, yet cannot identify their product as a probiotic in the marketplace because they have not received endorsement of their claims by the EU. This is not an issue resulting from an unclear definition, since probiotics surely should provide a health benefit, but rather from a lack of agreement as to what level of evidence is sufficient to substantiate a health benefit.

ISAPP remains committed to the importance of requiring a health benefit for the ‘biotic’ family of terms (outlined in the table below). It’s clear that all of these definitions are meaningless unless the requirement that they confer a health benefit is considered as essential by all stakeholders. One could reasonably discuss whether the required levels of evidence for foods and supplements are too high in some regulatory jurisdictions, but the value of these substances collapses in the absence of a health benefit.

Summary of ISAPP consensus definitions

With the publication of the most recent ISAPP consensus paper, this one on postbiotics, I offer a summary below of the five consensus definitions published by ISAPP. Each definition is part of a comprehensive paper resulting from focused discussions among experts in the field and published in Nature Reviews Gastroenterology and Hepatology (NRGH). These papers are among the top most viewed of all time on the NRGH website and are increasingly cited by scientists and regulators.

Table. Summary of ISAPP Consensus Definitions of the ‘Biotics’ Family of Substances. Probiotics, prebiotics, synbiotics and postbiotics have in common the requirement for a health benefit. They may apply to any target host, any regulatory category and must be safe for their intended use. Fermented foods fall only under the foods category and no health benefit is required.

Definition Key features of the definition Reference
Probiotics Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host Grammatical correction of the 2001 FAO/WHO definition.

No mechanism is stipulated by the definition.

 

Hill et al. 2014
Prebiotics A substrate that is selectively utilized by host microorganisms conferring a health benefit Prebiotics are distinct from fiber. Beneficial impact on resident microbiota and demonstration of health benefit required in same study. Gibson et al. 2017
Synbiotics A mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host Two types of synbiotics defined: complementary and synergistic. Complementary synbiotics comprise probiotic(s) plus prebiotic(s), meeting requirements for criteria for each. Synergistic synbiotics comprise substrate(s) selectively utilized by co-administered live microbe(s), but independently, the components do not have to meet criteria for prebiotic or probiotic. Swanson et al. 2020
Postbiotics Preparation of inanimate microorganisms and/or their components that confers a health benefit on the host Postbiotics are prepared from live microbes that undergo inactivation and the cells or cellular structures must be retained. Filtrates or isolated components from the growth of live microbes are not postbiotics. A probiotic that is killed is not automatically a postbiotic; the preparation must be shown to confer a health benefit, as well as meet all other criteria for a postbiotic. Salminen et al. 2021
Fermented Foods Foods made through desired microbial growth and enzymatic conversions of food components Fermented foods are not the same as probiotics. They are not required to have live microbes characterized to the strain level nor have evidence of a health benefit. Types of fermented foods are many and are specific to geographic regions. Compared to the raw foods they are made from, they may have improved taste, digestibility, safety, and nutritional value. Marco et al. 2021

 

 

*Actually, there is one approved health claim in the EU for a probiotic: Scientific Opinion on the substantiation of health claims related to live yoghurt cultures and improved lactose digestion (ID 1143, 2976) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

 

Further reading: Defining emerging ‘biotics’

ISAPP publishes continuing education course for dietitians

For dietitians, it’s often difficult to find practical, up-to-date resources with a scientific perspective on probiotics, prebiotics, synbiotics and fermented foods. ISAPP is pleased to announce a new resource to fill this need – a Special Continuing Education Supplement in Today’s Dietitian titled, “Evidence-based use of probiotics, prebiotics and fermented foods for digestive health”. This free continuing education course also includes infographic summaries, links to supplementary information, and even some favourite recipes. US dietitians can earn 2.0 CPEUs for completing this self-study activity.

The resource was written by dietitian and assistant professor Dr. Hannah D. Holscher, along with two ISAPP board members, Prof. Robert Hutkins, a fermented foods and prebiotics expert, and Dr. Mary Ellen Sanders, a probiotic expert.

“We hope this course will give dietitians an overview of the evidence that exists for probiotics, prebiotics, synbiotics and fermented foods, and help explain some of the practical nuances around incorporating them into their practice,” says Sanders. “In addition, we believe that this course will be a scientifically accurate overview that can counter prevalent misinformation. It can serve as a useful resource for diverse array of professionals active in this field.”

Find the supplement here.

What’s the evidence on ‘biotics’ for health? A summary from five ISAPP board members

Evidence on the health benefits of gut-targeted ‘biotics’ – probiotics, prebiotics, synbiotics, and postbiotics – has greatly increased over the past two decades, but it can be difficult to sort through the thousands of studies that exist today to learn which of these ingredients are appropriate in which situations. At a recent World of Microbiome virtual conference, ISAPP board members participated in a panel that provided an overview of what we currently know about the health benefits of ‘biotics’ and how they are best used.

Here’s a summary of what the board members had to say:

Dr. Mary Ellen Sanders: Probiotics and fermented foods

  • Probiotics are “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”.
  • Unfortunately, published assessments of probiotic products available on the market show that these products often fall short of required evidence. For example, their labels may not adequately describe the contents (including genus / species / strain in the product); they may not guarantee the efficacious dose through the end of the shelf life.
  • Contrary to common belief, probiotics do not need to colonize in the target site (e.g. the gut), impact gut microbiota composition, be derived from humans, or be resistant to stomach acid and other gut secretions such as bile.
  • Fermented foods are those made “through desired microbial growth and enzymatic conversions of food components”. The recent increased interest in fermented foods may come from people’s increased awareness of the role of gut microbes in overall health, but it is important to note that we have little direct evidence that the transient effects of fermented food microbes on the gut microbiota actually lead to health benefits. With that said, observational studies suggest that consuming some traditional fermented foods is associated with improved health outcomes.

Prof. Dan Merenstein, MD: Probiotics – How do I know what to prescribe for adult health?

  • A (limited) survey showed that most dietary supplement probiotic products cannot be linked to evidence because they do not provide enough information to determine what evidence exists to support their use – especially strains in the product. However, there are some probiotic products that have robust evidence.
  • Should every adult take a probiotic? The best evidence supports probiotics for improved lactose digestion and for prevention of difficile infection. Probiotics have also been shown to prevent common illnesses; reduce the duration of gut symptoms; and perhaps even reduce antibiotic consumption.
  • Studies will reveal more about the microbiome and about how probiotics work, for whom and for what indications. As with diet, the answer will most likely not be same for each person.

Prof. Glenn Gibson: Prebiotics and Synbiotics

  • A prebiotic is “a substrate that is selectively utilized by host microorganisms conferring a health benefit”. Researchers can test these substances’ activity in various ways: batch cultures, micro batch cultures, metabolite analysis, molecular microbiology methods, CF gut models, with in vivo (e.g. human) studies being required. Prebiotics appear to have particular utility in elderly populations, and may be helpful in repressing infections, inflammation and allergies. They have also been researched in clinical states such as IBS, IBD, autism and obesity related issues (Gibson et al., 2017).
  • A synbiotic is “a mixture, comprising live microorganisms and substrate(s) selectively utilized by host microorganisms, that confers a health benefit on the host.” While more studies are needed to say precisely which are useful in which situations, synbiotics have shown promise for several aspects of health in adults (Swanson et al. 2020): surgical infections and complications, metabolic disorders (including T2DM and glycaemia), irritable bowel syndrome, Helicobacter pylori infection and atopic dermatitis.

Prof. Hania Szajewska, MD: Biotics for pediatric use

  • Beneficial effects of ‘biotics’ are possible in pediatrics, but each ‘biotic’ needs to be evaluated separately. High-quality research is essential.
  • It is important that we view the use of ‘biotics’ in the context of other things in a child’s life and other interventions.
  • Breast milk is the best option for feeding infants
  • If breastfeeding is not an option, infant formulae supplemented with probiotics and/or prebiotics and/or postbiotics are available on the market.
  • Pro-/pre-/synbiotic supplemented formulae evaluated so far seem safe with some favorable clinical effects possible, but the evidence is not robust enough overall to be able to recommend routine use of these formulae.
  • Evidence is convincing on probiotics for prevention of necrotizing enterocolitis in preterm infants.
  • Medical societies differ in their recommendations for probiotics to treat acute gastroenteritis in children – they appear beneficial but not essential.
  • Synbiotics are less studied, but early evidence indicates they may be useful for preventing sepsis in infants and preventing / treating allergy and atopic dermatitis in children.

Prof. Gabriel Vinderola: Postbiotics

  • The concept of non-viable microbes exerting a health benefit has been around for a while, but different terms were used for these ingredients. Creating a scientific consensus definition will improve communication with health professionals, industry, regulators, and the general public. It will allow clear criteria for what qualifies as a postbiotic, and allow better tracking of scientific papers for future systematic reviews and meta-analyses.
  • The ISAPP consensus definition (in press) of a postbiotic is: “A preparation of inanimate microorganisms and/or their components that confers a health benefit on the host”.
  • Postbiotics are stable, so no cold-chain is needed to deliver them to the consumer. Safety is of less concern because the microbes are not alive and thus cannot cause bacteraemia.
  • Research in the coming years will reveal more about postbiotics and the ways in which they can promote human health.

See here for the entire presentation on Biotics for Health.

Probiotics and fermented foods, by Dr. Mary Ellen Sanders (@1:15)

Postbiotics, by Prof. Gabriel Vinderola (@18:22)

Prebiotics and synbiotics, by Prof. Glenn Gibson (@33:24)

‘Biotics’ for pediatric use, by Prof. Hania Szajewska (@47:55 )

Probiotics: How do I know what to prescribe for adult health? by Prof. Dan Merenstein (@1:04:51)

Q&A (@1:20:00)

 

Probiotics in fridge

Designing Probiotic Clinical Trials: What Placebo Should I Use?

By Daniel J. Merenstein, MD, Professor, Department of Family Medicine and Director of Research Programs, Georgetown University Medical Center, Washington DC

Specifying a placebo is one of the most important decisions for a clinical trialist. The first trial I led was a study giving Benadryl to kids to see if it helped them sleep. We spent hours working with our pharmacist on the placebo to make sure it had the same sweet cherry taste of the active drug, Benadryl. We didn’t want parents to be able to determine whether they were randomized to Benadryl or the placebo by comparing the study product to what they had at home. Do study subjects really do this? Yes. Early in my career I was helping an orthopedist who was putting pain pumps directly into a patient’s ankle post-surgery in order to see if it would decrease oral narcotic usage. One of our first patients pulled his pump out, tasted the medicine and called us late at night complaining he was in the saline (placebo) group.

When undertaking a study on probiotics, and specifically probiotic yogurts, we can debate for weeks about the best placebo. Our intervention is yogurt fortified with an additional probiotic. Therefore, our intervention yogurt contains both the starter lactic acid bacteria and the probiotic. So assuming we want both groups to get nutritionally equivalent yogurt that can be blinded our placebo options could be as follows. Note that in recent years, we have become more cognizant that dead microbes may not be biologically inactive.

Placebo Microbiological content of Placebo Research question addressed
Yogurt Live starter cultures, no probiotic What is the contribution of probiotics to any health benefit?
Acidified yogurt No live or dead microbes What is the contribution of live probiotic + live starter cultures to any health benefit?
Heat treated yogurt No live microbes, dead starter microbes Beyond any contribution of dead starter cultures, what is the contribution of live probiotic + live starter cultures to the health benefit?
Heat treated probiotic yogurt No live microbes, dead starter + dead probiotic microbes Beyond any contribution of dead probiotics + dead starter cultures, what is the contribution of live probiotic + live starter cultures to the health benefit?
Probiotic yogurt using a different probiotic Live starter cultures, live probiotic different from the probiotic in the intervention What is the contribution of the intervention probiotic to any health benefit compared to the control probiotic?

 

We chose regular yogurt (the first option above) and now about eight papers later, I would say that about 50% of reviewers question our choice.

There are many reasons the placebo needs to be well considered, including the specific research question under consideration. But an important one is clinical equipoise, “a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial”, as defined Freedman 1987. Thus, for example in a study of a new hypertension drug, one cannot use a placebo that has no chance of lowering a patient’s blood pressure as a comparator as that is ethically indefensible. Instead, a well proven hypertension drug will be studied versus the new experimental drug.

For most of my career the goal in my studies was to pick a placebo that was as inactive as possible that still smelled, looked and tasted like my active intervention. However, the times are changing. When I started working there were fewer than 200 randomized controlled clinical probiotic trials retrievable from PubMed; today the number is over 2,300. Well that means we have gone beyond merely recognizing the value of probiotics in different indications, to detailed comparisons of different probiotic and non-probiotic interventions, so one has to consider how inactive their placebo is for probiotic intervention trials.

In 2020 the American Gastrointestinal Association came out with recommendations and guidelines after they conducted a thorough review of probiotic evidence. (See ISAPP blog ISAPP take-home points from American Gastroenterological Association guidelines on probiotic use for gastrointestinal disorders.) For three indications, they recommended using select probiotics over no or other probiotics, in populations of preterm low birthweight infants, patients receiving antibiotics, and patients with pouchitis. So what does this mean for trials evaluating one of these indications? It means that the placebo should be an active control, a probiotic versus probiotic trial.

Today if I’m asked what placebo should be used, my first question is what indication are you studying? If you are studying infant colic or preterm low birthweight infants, I think you need an active control, such as another probiotic. (Colleagues and I suggested this for probiotic studies on necrotizing enterocolitis in 2013.) If you are studying anxiety, then an inert placebo makes the most sense since insufficient evidence exists for any probiotic for this endpoint as yet. In the case of antibiotic associated diarrhea, it will be a much longer discussion as the data are not clear, but it would be reasonable for an IRB to argue that your placebo should be another probiotic. It is not ethical to deny a placebo group an effective intervention if one is available.

So in the last 15 years of my career the answer to what placebo should I use has greatly changed. As probiotic research has advanced, so has the evidence base for usage. As we proceed with research we now need to consider conducting our clinical trials differently. This is just another example of how probiotic evidence has matured over a relatively short period of time.

Video Presentation: Behind the scenes of the consensus panel discussion on the definition of fermented foods

Numerous misunderstandings and questions exist around the concept of fermented foods. For example:

  • If a food does not contain live microorganisms, can it still be a fermented food?
  • Should the live microbes in fermented foods be called probiotics?
  • Do fermentation microbes colonize the human gut?

The first step in answering these questions is for scientists to come to agreement on what constitutes a fermented food. A new global definition of fermented foods was recently published by 13 interdisciplinary scientists from various fields—microbiology, food science and technology, immunology, and family medicine. In their paper in Nature Reviews Gastroenterology & Hepatology, fermented foods are defined as: “foods and beverages made through desired microbial growth and enzymatic conversions of food components”.

The panel discussion and the definition of fermented foods are covered in this video presentation by the paper’s first author Prof. Maria Marco, from the Department of Food Science and Technology at the University of California, Davis. This presentation was originally given at the virtual ISAPP 2020 annual meeting.

The new definition is intended to provide a clearer conceptual understanding of fermented foods for the public and industry, with the authors expecting that in the years ahead, scientists will undertake more hypothesis-driven research to determine the extent that various fermented foods improve human health and precisely how this occurs. More studies that address fermented foods in promoting health will be useful for establishing the importance of fermented foods in dietary guidelines.

The panel acknowledged that regulations on fermented foods from country to country are mainly concerned with food safety — and that, when properly made, fermented foods and their associated microorganisms have a long history of safe use.

 

Can fermented or probiotic foods with added sugars be part of a healthy diet?

By Dr. Chris Cifelli, Vice President of Nutrition Research, National Dairy Council, Rosemont IL, USA

What about added sugar in fermented or probiotic foods? I am almost always asked this question whenever I give a nutrition presentation, no matter the audience. It’s not a surprising question as people care about what they eat and, often, are looking for ways to reduce their intake of sugar. Yet, if someone wants to add fermented or probiotic foods such as yogurt, kefir or kombucha to their diet, they often find the products available to them contain sugar as an added ingredient.

Should these products be part of you and your family’s healthy eating plan even if they have added sugar? The simple answer – yes, they likely can still fit into a healthy eating plan.

According to the U.S. Food and Drug Administration, ‘added sugars’ are defined as sugars that are either added during the processing of foods or are packaged separately as sugars (e.g. the bag of sugar you buy to make your treats). Added sugars in the diet have received attention because of their link to obesity and chronic disease risk. The World Health Organization, American Heart Association, Dietary Guidelines for America, and American Diabetes Association all recommend reducing added sugar intake to improve overall health. While data from the US National Health and Nutrition Examination Survey (NHANES) has shown that consumption of added sugar decreased from the 2007-2010 to the 2013-2017 surveys, the most recent Dietary Guidelines Advisory Committee report noted that the mean usual consumption of added sugars was still 13% of daily energy in 2015-16, which exceeds recommendations of 10%.

Including fermented foods in one’s diet may be important for overall health. The recent ISAPP consensus paper on fermented foods indicated that fermented foods, especially the live microbes contained in them, could benefit health in numerous ways, such as by beneficially modulating the gut microbiota or the immune system. Similarly, foods with added probiotics may confer health benefits ranging from impacting digestive health to metabolic parameters, depending on the probiotic contained in the product. Our understanding of the gut microbiota continues to evolve, but one thing is for certain: it is important for health. This provides a compelling reason to find ways to include these foods in healthy eating patterns.

So, back to the question at hand. Should you reduce or eliminate fermented foods and foods with probiotics from your diet if they have added sugars? Just like a “spoonful of sugar helps the medicine go down,” a little added sugar to improve the palatability of nutrient-dense foods is okay. Indeed, government and health organizations all agree that people can eat some sugar within the daily recommendations (which is 10% of total daily calories), especially in foods like yogurt or whole-grain cereals, or other healthy foods. And, there is no scientific evidence to show that the sugar in these products reduces the health benefits associated with eating foods like yogurt or probiotics. Human studies assessing health benefits of probiotic foods typically use products with added sugar, yet health effects are still observed.

The next time you are out shopping you can choose your favorite fermented or probiotic-containing food guilt free, as long as you’re watching your overall daily intake of sugar. But, if are you are still concerned, then choose plain varieties to control your own level of sweetness or you could opt for a probiotic supplement to avoid the sugar. Whether you go with the sweetened or unsweetened version of your favorite fermented food, you’ll not only get the benefit of the live microbes in these products but also the nutritional benefit that comes with foods like yogurt.

 

Creating a scientific definition of ‘fermented foods’

By Prof. Maria Marco, Department of Food Science and Technology, University of California Davis, USA

A panel of scientific experts was recently convened by ISAPP to discuss the state of knowledge on fermented foods. While there was much agreement on the underlying microbiological processes and health-related properties of those foods and beverages, our conversation on definitions led to sustained debate. So what exactly is a fermented food?

The word “ferment” originates from fervere, which in Latin means to boil. According to the Merriam-Webster dictionary, the verb ferment is defined as “to undergo fermentation or to be in a state of agitation or intense activity”. Fermentation is defined as both a chemical change with effervescence and as an enzymatically controlled anaerobic breakdown of energy-rich compounds (such as a carbohydrate to carbon dioxide and alcohol or to an organic acid). In biochemistry, fermentation is understood as an ATP-generating process in which organic compounds act as both electron donors and acceptors. In industry, fermentation means the intentional use of bacteria and eukaryotic cells to make useful products such as drugs or antibiotics. As you can see, there are clearly many meanings implied in “ferment” and “fermentation”. We add onto this by defining how those words apply to foods.

As our ISAPP panel began to deliberate the definition of fermented foods, it quickly became clear how difficult reaching consensus can be! Even though many panel members shared similar academic backgrounds and scientific expertise, finding agreement on the definition required several rounds of debate and some consuming of fermented foods and beverages along the way. Finally, we defined fermented foods and beverages as being “foods made through desired microbial growth and enzymatic conversions of food components” (see the published consensus paper here).

Find ISAPP’s infographic on fermented foods here.

This definition is very specific by requiring microbial growth and enzymatic processes for the making of those foods. Activity of the endogenous enzymes from the food components or enzymes added to the food is not enough for a food to be regarded as fermented. Similarly, foods made by only adding vinegar or “pickling” should not be called fermented. The definition acknowledges the essential roles of microorganisms for making fermented foods but does not require their presence or viability at the time of consumption.

On the other hand, our definition does not restrict fermented foods to only those foods and beverages made using microorganisms using metabolic pathways implicit in the strict biochemical definition. Yogurt and kimchi made using lactic acid bacteria relying on fermentative energy metabolism are included as much as koji and vinegar, foods made using fermentation processes that employ fungi and bacteria that perform aerobic respiratory metabolism.

Each word in a definition needs to be carefully calibrated. The best example of this in our definition of fermented foods is the word “desired”. Unlike a food that is spoiled as a result of microbial growth and enzymatic activity, food fermentations generate wanted attributes. Other words such as “intentional”, “desirable”, or “controlled” may also be used to describe this meaning. However, those words also have caveats that not all fermented foods are made “intentionally”, at least in the way that they were first prepared thousands of years ago. Qualities of fermented foods may be “desirable’ in some cultures but not others. While some fermentations are “controlled”, others are spontaneous, requiring little human input.

The process of discussing the definition with a group of scientific experts was enlightening because it required us to deconstruct our individual assumptions of the term in order to reach agreement on descriptions and meaning. With a definition in hand, we can use a shared language to study fermented foods and to communicate on the significance of these foods and beverages in our diets. There will also certainly be more “fermenting” of these concepts to improve our knowledge on the production and health impacting properties of fermented foods for years to come.

Find the ISAPP press release on this paper here.

Read about another ISAPP-led publication on fermented foods here.

Learn more in a webinar on the science of fermented foods here.

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

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.

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

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)

Bulgarian yogurt: An old tradition, alive and well

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.

ISAPP’s popular educational videos now feature subtitles in multiple languages

ISAPP’s series of six English-language videos are a useful resource for helping consumers answer important questions about probiotics, prebiotics, and fermented foods. In order to make these popular educational videos accessible to a wider global audience, ISAPP has now updated them with subtitles in multiple languages: Dutch, French, German, Indonesian, Italian, Japanese, Russian, and Spanish.

Dr. Roberta Grimaldi, a principal clinical research scientist who served as ISAPP’s Industry Advisory Committee representative from 2017-2019, led the video subtitling efforts.

“The videos are a good way to communicate information about these products, which are still not fully understood by consumers,” says Grimaldi. She says that while consumers see “a lot of miscommunication and misleading information” online, the easy-to-understand ISAPP videos help bring the scientific perspective to a broad audience.

Multi-lingual members of the ISAPP community stepped up to help with the translations, with Grimaldi managing the task and co-ordinating with the video production agency. She says, “It was definitely an amazing team effort, which I think gave us really great results.”

Science Translation Committee head Dr. Chris Cifelli underlines how worthwhile the video subtitles project has been for ISAPP. “Since ISAPP is an international organization, we have been working hard to make our educational materials accessible to as many people as possible. The subtitles allow the information in these videos to be shared much more widely, ultimately helping consumers make more informed decisions about probiotics, prebiotics, and fermented foods.”

Many of ISAPP’s infographics are also available in multiple languages.

 

How to change the language subtitles on an ISAPP video:

Step 1 – On the ISAPP videos page, click on the video.

Step 2 – Press pause and click the gear-like ‘Settings’ icon, to the right of the ‘CC’ icon.

Step 3 – Click on ‘Subtitles’ and select the language subtitle you prefer.

Step 4 – Resume the video by pressing play.

ISAPP welcomes three new board members

By Mary Ellen Sanders, PhD, ISAPP Executive Science Officer

ISAPP is pleased to announce that Profs. Kelly Swanson PhD, Daniel Tancredi PhD, and Gabriel Vinderola PhD have joined the ISAPP board of directors. The expertise of these three globally recognized academic experts complements that of the current board members, together comprising a leading global group of distinguished scientific and clinical experts in the fields of probiotics, prebiotics, synbiotics, fermented foods, and postbiotics.

Read more about ISAPP’s newest board members:

Kelly Swanson is the Kraft Heinz Company Endowed Professor in Human Nutrition, a professor in the Department of Animal Sciences and Division of Nutritional Sciences and an adjunct professor in the Department of Veterinary Clinical Medicine at the University of Illinois at Urbana-Champaign. He is an expert in the field of fiber and prebiotics, and brings to ISAPP knowledge of application of these substances to companion and agricultural animals. Kelly, who trained with previous ISAPP Board member, George Fahey, is considered one of the top authorities in animal gut health, microbiome, and nutrition. His research has focused on testing the effects of nutritional intervention on health outcomes, identifying mechanisms by which nutrients impact gastrointestinal microbiota, host gene expression, and host physiology. Kelly served on the prebiotic consensus panel (here), led the ISAPP synbiotics consensus panel, and is lead author on the synbiotics outcome paper, currently in press with Nature Reviews Gastroenterology and Hepatology.

Dan Tancredi is a biostatistician with an appointment as an Associate Professor (full professor starting July 1, 2020) in Residence at UC Davis Department of Pediatrics, and is also with the Center for Healthcare Policy and Research. Dan works extensively on NIH-sponsored research and as an NIH scientific reviewer. He has an extensive record of collaboration with ISAPP; he has served as an invited expert and/or speaker at all but one ISAPP meeting since 2009, providing his perspectives on how to improve the quality and scientific impact of probiotic trials and how to conduct systematic reviews that rigorously and transparently synthesize the evidence from these trials. He has been a co-author on 6 ISAPP papers (here, here, here, here, here, here and here), including a 2020 paper “Probiotics as a Tx Resource in Primary Care” published in the Journal of Family Practice (see New publication gives a rundown on probiotics for primary care physicians). Dan was invited to author the Nature commentary on the landmark probiotics trial by Panigrahi, et al. for reducing newborn sepsis in the developing world—showing his reputation as a trusted voice for assessing the quality of probiotic research.

Gabriel Vinderola is a professor at National University of Litoral, Santa Fe, Argentina and Principal Researcher at CONICET, at the Dairy Products Institute (UNLCONICET). He is an expert in lactic acid bacteria, fermented foods, and probiotics. Gabriel has forged academic collaborations with academic and industrial scientists in numerous countries in Europe and with industrial colleagues in Argentina. He has been active in several countries in South America working with regulators to assure that their actions on probiotic guidelines are science-based, including his recent efforts consulting on guidelines for probiotics for the Codex Alimentarius. He has written blogs for ISAPP, translated ISAPP videos and infographics into Spanish, and was an expert on the ISAPP consensus panel on postbiotics. His research has focused on technological aspects of probiotics (biomass production, dehydration, storage, food matrices) and fermented foods. He is an active public science communicator in Argentina on the topics of probiotics, prebiotics, fermented foods, and the microbiome. See Growing interest in beneficial microbes and fermented foods in Argentina for some examples. Gabriel represents the first ISAPP board member from South America and we anticipate his involvement will help ISAPP expand its presence and connections in Latin America.