Are probiotics effective in improving symptoms of constipation?

By Eirini Dimidi, PhD, Lecturer at King’s College London

Constipation is a common disorder that affects approximately 8% of the general population and is characterised by symptoms of infrequent or difficult bowel movements (1). People who suffer with constipation often report that it negatively affects their quality of life and the majority use some sort of treatment, such as fibre supplements and laxatives, to alleviate their symptoms (2). However, approximately half of those report they are not completely satisfied with the treatment options currently available to them, mainly due to lack of effectiveness in improving their symptoms (2).

Could probiotics offer an effective alternative way to treat constipation symptoms?

Our team at the Department of Nutritional Sciences at King’s College London has investigated the potential benefits of probiotic supplements in chronic constipation. We have extensively reviewed the available evidence on their mechanisms of action in affecting gut motility and their effectiveness in improving symptoms, and we have also conducted a randomised controlled trial of a novel probiotic in 75 people with chronic constipation (3-5).

USE OF PROBIOTICS

Before looking at the evidence on the effectiveness of probiotics in constipation, it is easy to see that some people with constipation already choose to try probiotics for their gut health. A national UK survey of over 2,500 members of the public, which included people with and without constipation, showed that people with constipation have a 5.2 higher chance of currently using probiotics for gut health, compared to people who don’t suffer from it (3).

However, the majority of doctors do not recommend probiotics for the relief of constipation symptoms, nor do they believe there is enough evidence to support their use in this condition (3).

So, what is the current evidence on probiotics and constipation?

MECHANISMS OF ACTION OF PROBIOTICS

Probiotics may impact gut motility and constipation through several mechanisms of action. Depending on the strain, they may affect the number and composition of gut microbes, as well as the compounds they release. The gut microbiota and their released compounds can then interact with our immune and nervous system, with the latter being the primary regulator of gut motility, ultimately improving constipation symptoms. Therefore, there is a rationale to support a potential improvement in constipation. But is this supported by evidence from clinical trials?

EFFECTIVENESS OF PROBIOTICS

A systematic review of the literature showed Bifidobacterium lactis strains appear to improve several symptoms of constipation, such as infrequent bowel movements and hard stools (4). At the same time, other probiotic species did not improve any symptoms. This is an important finding as it highlights that not all probiotics have the same effects in constipation, and that only certain probiotics may improve constipation. Therefore, people with constipation may only benefit from specific probiotic products – but which products would those be? Since the systematic review above showed that several B. lactis strains were effective, does this means that people with constipation may benefit from any B. lactis-containing product?

Unfortunately, it is a bit more complicated. Since the publication of the aforementioned review, new studies have been published showing that, while some probiotic products with B. lactis are effective, various other B. lactis probiotics do not impact constipation (5-6). This may be explained by strain-specific effects, but also other methodological differences among studies (e.g. probiotic dose).

TAKE HOME MESSAGE

Can we recommend probiotics for the management of constipation? At the moment, there is some low quality evidence to support the use of certain Bifidobacterium lactis strains to help manage symptoms of constipation. Further high-quality studies are needed to clarify which specific probiotic strains may be effective. However, given that there is some evidence in this area (albeit limited), along with the fact probiotics are safe for the general population to consume (unless clinically contraindicated), people with constipation could try a probiotic product of their choice for four weeks, should they wish to, bearing in mind the uncertainty in the evidence so far. But scientists continue to work to answer this question because the evidence is promising enough to warrant continued study of probiotics for constipation.

 

    1. Palsson, Gastroenterol 2020;158:1262-1273
    2. Johanson & Kralstein, Aliment Pharmacol Ther 2007;25(5):599-608
    3. Dimidi et al, Nutrition 2019;61:157-163
    4. Dimidi et al, Am J Clin Nutr 2014;100(4):1075-84
    5. Dimidi et al, Aliment Pharmacol Ther 2019;49:251-264
    6. Wang et al, Beneficial Microbes 2021;12:31-42

 

 

Can diet shape the effects of probiotics or prebiotics?

By Prof. Maria Marco PhD, University of California – Davis and Prof. Kevin Whelan PhD, King’s College London

If you take any probiotic or prebiotic product off the shelf and give it to several different people to consume, you might find that each person experiences a different effect. One person may notice a dramatic reduction in gastrointestinal symptoms, for example, while another person may experience no benefit. On one level this is not surprising, since every person is unique. But as scientists, we are interested in finding out exactly what makes a person respond to a given probiotic or prebiotic to help healthcare providers know which products to recommend to which people.

Among factors that might impact someone’s response to a probiotic or prebiotic – such as baseline microbiota, medications, and host genetics – diet emerges as a top candidate. Ample evidence has emerged over the past ten years that diet has direct and important effects on the structure and function of the gut microbiome. Overall the human gut microbiome is shaped by habitual diet (that is, the types of foods consumed habitually over time), but the microbes can also can fluctuate in response to short-term dietary shifts. Different dietary patterns are associated with distinct gut microbiome capabilities. Since probiotics and prebiotics may then interact with gut microbes when consumed, it is plausible that probiotic activity and prebiotic-mediated gut microbiome modulation may be impacted by host diet.

A discussion group convened at ISAPP’s 2022 annual meeting brought together experts from academia and industry to address whether there is evidence to support the impact of diet on the health effects of probiotics and prebiotics. To answer this question, we looked at how many probiotic or prebiotic studies included data on subjects’ diets.

  • Prebiotics: Our review of the literature showed that only a handful of prebiotic intervention studies actively measured background diet as a potential confounder of the effect of the prebiotic. One such study (Healey, et al., 2018) classified individuals based on habitual fiber intake, and in doing so found that the gut microbiome of individuals consuming high fiber diets exhibited more changes to microbiome composition than individuals with low fiber intake. While both groups consuming prebiotics showed enrichment of Bifidobacterium, those with high fiber intake uniquely were enriched in numerous other taxa, including butyrate-producing groups of microbes. Prebiotics also resulted in improved feelings of satiety, but only among the high fiber diet consumers.
  • Probiotics: We found no evidence of published human RCTs on probiotics that investigated diet as a possible confounding factor. This is a significant gap, since we know from other studies that host diet affects the metabolic and functional activity of probiotic lactobacilli in the digestive tract. Moreover, the food matrix for the probiotic may further shape its effects, via the way in which the probiotic is released in situ.

Our expert group agreed that diet should be included in the development of new human studies on probiotics and prebiotics, as well as other ‘-biotics’ and fermented foods. These data are urgently needed because although diet may be a main factor affecting outcomes of clinical trials for such products, it is currently a “hidden” factor.

We acknowledge there will be challenges in taking diet into account in future trials. For one, should researchers merely record subjects’ habitual dietary intake, or should they provide a prescribed diet for the duration of the trial? The dietary intervention (nutrient, food, or whole diet) must also be clearly defined, and researchers should carefully consider how to measure diet (e.g. using prospective or retrospective methods). In the nutrition field, it is well known that there are challenges and limitations in the ways dietary intake is recorded as well as the selection of dietary exclusion criteria. Hence, it is crucial that dietitians knowledgeable in dietary assessment and microbiome research contribute to the design of such trials.

If more probiotic and prebiotic trials begin to include measures of diet, perhaps we will get closer to understanding the precise factors that shape someone’s response to these products, ultimately allowing people to have more confidence that the product they consume will give them the benefits they expect.

Human milk oligosaccharides as prebiotics to be discussed in upcoming ISAPP webinar

Human milk oligosaccharides (HMOs), non-digestible carbohydrates found in breast milk, have beneficial effects on infant health by acting as substrates for immune-modulating bacteria in the intestinal tract. The past several years have brought an increase in our understanding of how HMOs confer health benefits, prompting the inclusion of synthetic HMOs in some infant formula products.

These topics will be covered in an upcoming webinar, “Human milk oligosaccharides: Prebiotics in a class of their own?”, with a presentation by Ardythe Morrow PhD, Professor of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine. The webinar will provide an overview of what HMOs are, how they are breaking new ground with the types of health benefits they can provide to infants and the recent technological innovations that will facilitate their translation into new infant formulas.

Dr. Karen Scott, Rowett Institute, University of Aberdeen, and Dr. Margriet Schoterman, FrieslandCampina, will host the webinar. All are welcome to join this webinar, scheduled for Wednesday, Oct 19th, 2022, from 10-11 AM Eastern Daylight Time. Registration is free of charge. Spaces may be limited.

Register here.

A pediatrician’s perspective on c-section births and the gut microbiome

By Prof. Hania Szajewska, MD, Medical University of Warsaw, Poland and Kristina Campbell, MSc, ISAPP Consulting Communications Director

The decision to have a Cesarean section (C-section) should always depend on whether this is the best choice for the mother and baby, and it is never made by pediatricians. However, pediatricians are often asked about the consequences of C-section delivery for a child later in life and whether potential C-section-related harms may be reduced.

The data show that delivery by C-section is now more common than ever globally. The World Health Organization estimates the  C-section rate is around 21% of all births, and predicted to continue increasing. Although C-section rates are increasing both in developed and developing countries, Korea, Chile, Mexico, and Turkey have the highest rates in the world, with C-sections constituting 45% to 53% of all births. C-sections outnumber vaginal births in countries that include Dominican Republic, Brazil, Cyprus, Egypt, and Turkey.

Cesarean delivery is a medical procedure that can of course save an infant (or a mother) in a moment of danger, making birth less risky overall. But analyses have shown not all C-sections are initiated for safety reasons—some are driven by convenience and other non-medical factors. In areas with the highest C-section rates, only around half of the time are they required for life-saving reasons. Although the rate of medically necessary C-sections globally is difficult to establish, the WHO estimates it is between 10-15% of all births.

Non-essential C-sections would be perfectly reasonable if the health risks later in life were negligible. But are they? Scientific work in the past decade has shown that, in fact, there may be downsides to being born by C-section—and these health risks may manifest later in a child’s life.

By now, many observational studies have associated Cesarean births with an increased risk of various chronic health conditions that appear long after birth. C-section is associated with a higher risk of asthma and allergy, as well as obesity and type 2 diabetes. A systematic review and meta-analysis (incorporating 61 studies, which together included more than 20 million deliveries) also linked C-sections with autism spectrum disorders and attention deficit hyperactivity disorder (ADHD). Type 1 diabetes is also more prevalent in children born by c-section.

Since association is not the same as causation, scientists have looked at possible biological correlates of C-section and how they could be tied to future health problems. A leading hypothesis is that C-section deliveries cause health problems by disrupting the infant’s normal gut microbiota (i.e. the collection of microorganisms in specific ‘habitats’ on the infant’s body, such as the gut) within a critical time window for immune system development.

An altered microbiota in C-section births

One of the main clues about whether C-section births affect health via the microbiota is the consistent observation that infants born by C-section have a different collection of microorganisms in their digestive tracts and elsewhere on their bodies immediately after birth, compared with vaginally-born controls. Newborns delivered by C-section tend to harbor in their guts disease-causing microbes commonly found in hospitals (e.g. Enterococcus and Klebsiella), and lack strains of gut bacteria found in healthy children (e.g. Bacteroides species). Because it is known that gut microbiota are in close communication with the immune system, this difference in birth microbes may set the immune system up for later dysfunction.

However, an important confounding factor exists. Antibiotic administration is a recommended medical practice for C-section births in order to prevent infections. Antibiotics are potent disruptors of microbial communities – in this case the mother’s, or perhaps the infant’s if antibiotics are administered prior to umbilical cord clamping. It is not yet clear whether the timing of antibiotic administration can prevent such disruptions. (See conflicting evidence here and here; also see here.).

Gut microbiota disruption is associated with C-sections, but since C-section and antibiotics nearly always go together (with potential exposure of the infant to these drugs), it is not clear to what extent C-section and/or antibiotic treatments drive increased risk of chronic disease later in life. Antibiotic treatments within the first 2 years of life are independently associated with an increased risk of several conditions: childhood-onset asthma, allergic rhinitis, atopic dermatitis, celiac disease, overweight / obesity, and ADHD.

Options for microbiota ‘restoration’

If mechanistic studies continue to support the idea that the C-section-disrupted gut microbiota is the trigger for chronic diseases later in life, strategies could be proposed for ‘restoring’ or normalizing the infant gut microbiota after such births. Already some microbiota modifying interventions have been evaluated:

  • Probiotics: Undesired changes in microbiota composition and function caused by antibiotic treatments and/or caesarean birth may be addressed by probiotics—i.e. “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. In one study, a mixture of several probiotic strains along with at least partial breastfeeding shifted the infant gut microbiota toward a more favorable profile. Intriguingly, probiotics (of various strains) prevent IgE-associated allergy until age 5 years, specifically in cesarean-delivered children but not in all children.
  • Synbiotics: A study showed supplementation with scGOS/lcFOS and B. breve M-16V appeared to compensate for delayed Bifidobacterium colonization in the guts of C-section delivered infants.
  • Maternal vaginal microbial transfer (otherwise known as ‘vaginal seeding’ or ‘microbial bath’: This is a procedure in which infants born by C-section, immediately after birth, are swabbed with gauze that contains microbes from the mother’s vaginal tract. After the media attention given to early studies, there is increased demand from parents for this procedure. Although some studies have found it effective for normalizing the infant gut microbiota, safety is not completely established and it is too early for routine use of this procedure. Parents wishing to try this approach are advised to participate in a study as part of an institutional review board-approved research protocol.
  • Maternal fecal microbiota transplantation: This procedure involves fecal microbes from the mother, orally administered to C-section infants after birth. A proof-of-concept study showed that after this intervention the gut microbiota of C-section-born infants looked more similar to that of vaginally born infants. But for this procedure, as above, the risk of transmitting harmful microbes is a concern, making it too early to recommend the procedure unless it is part of an institutional review board-approved research protocol.
  • Breastfeeding: Breastfeeding is the gold standard for infant nutrition, and breast milk contains live microorganisms as well as other components that interact with the gut microbiota. Exclusive breastfeeding for about 6 months of C-section infants helps the gut microbiota shift toward a profile seen in vaginally born infants.

So far, probiotics, synbiotics, and microbiota ‘restoration’ are not sufficiently reliable solutions for correcting the microbiota disruptions that accompany C-section births. Further studies are needed to develop these approaches.

A leading strategy

At present, breastfeeding is the main strategy for supporting the infant gut microbiota after C-section for the greatest chance of avoiding negative health consequences. Breastfeeding has multiple benefits, but may be of increased importance after C-section birth. Mothers should be supported after giving birth by C-section to breastfeed the infant during this critical period of early life and immune system development.

 

Probiotics vs. prebiotics: Which to choose? And when?

By Dr. Karen Scott, PhD, Rowett Institute, University of Aberdeen, Scotland

As consumers we are constantly bombarded with information on what we should eat to improve our health. Yet the information changes so fast that it sometimes seems that what was good for us last week should now be avoided at all costs!

Probiotics and prebiotics are not exempt from such confusing recommendations, and one area lacking clarity for many is which of them we should pick, and when. In this blog I will consider the relative merits of probiotics and prebiotics for the gut environment and health.

By definition, both probiotics and prebiotics should ‘confer a health benefit on the host’. Since an improvement in health can be either subjective (simply feeling better) or measurable (e.g. a lowering in blood pressure) it is clear that there is not a single way to define a ‘health benefit’. This was discussed nicely in a previous blog by Prof Colin Hill.

Although consumption of both probiotics and prebiotics should provide a health benefit, this does not mean that both need to act through the gut microbiota. Prebiotics definitively need to be selectively utilised by host microorganisms – they are food for our existing microbiota. However, depending on the site of action, this need not be the gut microbiota, and prebiotics targeting other microbial ecosystems in or on the body are being developed. Traditionally prebiotics have specifically been used to boost numbers of gut bacteria such as Bifidobacterium and the Lactobacilliaceae family, but new prebiotics targeting different members of the gut microbiota are also currently being researched.

Probiotics are live bacteria and despite a wealth of scientific evidence that specific probiotic bacterial strains confer specific health benefits, we often still do not know the exact mechanisms of action. This can make it difficult both to explain how or why they work, and to select new strains conferring similar health benefits. Many probiotics exert their effects within the gut environment, but they may or may not do this by interacting with the resident gut microbiota. For instance probiotics that reduce inflammation do so by interacting directly with cells in the mucosal immune system. Yet strains of lactobacilli (see here for what’s included in this group of bacteria) may do this by modulating cytokine production while Bifidobacterium strains induce tolerance acquisition. These very different mechanisms are one reason why mixtures containing several probiotic species or strains may in the end prove the most effective way to improve health. On the other hand, some probiotics do interact with the resident gut microbes: probiotics that act by inhibiting the growth of pathogenic bacteria clearly interact with other bacteria. Sometimes these may be potential disease-causing members of the resident microbiota, normally kept in check by other commensal microbes that themselves have become depleted due to some external impact, and some may be incoming pathogens. Such interactions can occur in the gut or elsewhere in the body.

This brings me back to the original question, and one I am frequently asked – should I take a probiotic or a prebiotic? The true and quick answer to this question is ‘it depends’! It depends why you are asking the question, and what you want to achieve. Let’s think about a few possible reasons for asking the question.

I want to improve the diversity of my microbiota. Should I take a prebiotic or a probiotic?

My first reaction was that there is an easy answer to this question – a prebiotic. Prebiotics are ‘food’ for your resident bacteria, so it follows that if you want to improve the diversity of your existing microbiota you should take a prebiotic. However, in reality this is too simplistic. Since prebiotics are selectively utilised by a few specific bacteria within the commensal microbiota to provide a health benefit, taking a prebiotic will boost the numbers of those specific bacteria. If the overall bacterial diversity is low, this may indeed improve the diversity. However, if the person asking the question already has a diverse microbiota, although taking one specific prebiotic may boost numbers of a specific bacterium, it may not change the overall diversity in a measurable way. In fact the best way to increase the overall diversity of your microbiota is to consume a diverse fibre-rich diet – in that way you are providing all sorts of different foods for the many different species of bacteria living in the gut, and this will increase the diversity of your microbiota.  Of course, if you already consume a diverse fibre-rich diet your microbiota may already be very diverse, and any increased diversity may not be measurable.

I want to increase numbers of bifidobacteria in my microbiota. Should I take a prebiotic or a probiotic?

Again, I initially thought this was easy to answer – a prebiotic. There is a considerable amount of evidence that prebiotics based on fructo-oligosaccharides (FOS or inulin) boost numbers of bifidobacteria in the human gut. But this is only true as long as there are bifidobacteria present that can be targeted by consuming suitable prebiotics. Some scientific studies have shown that there are people who respond to prebiotic consumption and people who do not (categorised as responders and non-responders). This can be for two very different reasons. If an individual is devoid of all Bifidobacterium species completely, no amount of prebiotic will increase bifidobacteria numbers, so they would be a non-responder. In contrast if someone already has a large, diverse bifidobacteria population, a prebiotic may not make a meaningful impact on numbers – so they may also be a non-responder.

However, for those people who do not have any resident Bifidobacterium species, the only possible way to increase them would indeed be to consume a probiotic- specifically a probiotic containing one or several specific Bifidobacterium species. Consuming a suitable diet, or a prebiotic alongside the probiotic, may help retention of the consumed bifidobacteria, but this also depends on interactions with the host and resident microbiota.

I want to increase numbers of ‘specific bacterium x’ in my microbiota. Should I take a prebiotic or a probiotic?

The answer here overlaps with answer 2, and depends on the specific bacterium, and what products are available commercially, but the answer could be to take either, or a combination of both – i.e. a synbiotic.

If bacterium x is available as a probiotic, consuming that particular product could help. If bacterium x has been widely researched, and the specific compounds it uses for growth have been established, identifying and consuming products containing those compounds could boost numbers of bacterium x within the resident microbiota. Such research may already have identified combination products – synbiotics – that could also be available.

One caveat for the answers to questions 2 and 3 is that probiotics do not need to establish or alter the gut microbiota to have a beneficial effect on health. In fact, a healthy large intestine has a microbial population of around 1011-1012 bacterial cells per ml, or up to 1014 cells in total, while a standard pot of yogurt contains 1010 bacterial cells (108 cells/ml). Assuming every probiotic bacterial cell reaches the large intestine alive, they would be present in a ratio of 1: 10,000. This makes it difficult for them to find a specific niche to colonise, so consuming a probiotic may not “increase numbers of ‘specific bacterium x’ in my microbiota”, but this does not mean that the function of the probiotic within the gut ecosystem would not provide a health benefit. Many probiotics act without establishing in the microbiota.

I’ve been prescribed antibiotics. Should I take a prebiotic or a probiotic?

In this case the answer is clear cut – a probiotic.

There is a lot of evidence that consumption of probiotics can alleviate symptoms of, or reduce the duration of, antibiotic associated diarrhoea. From what we know about mechanisms of action, consumption of antibiotics kills many resident gut bacteria, reducing the overall bacterial population and providing an opportunity for harmful bacteria to become more dominant. Consuming certain probiotics can either help boost bacterial numbers in the large intestine, preventing the increased growth in pathogenic bacteria until the resident population recovers, or can increase production of short chain fatty acids, decreasing the colonic pH, preventing growth of harmful bacteria. Ideally probiotics would be taken alongside antibiotics, from day 1, to avoid the increase in numbers of the potentially harmful bacteria in the first place. This has been shown to be more effective. Consuming the probiotic alongside prebiotics that could help the resident microbiota recover more quickly may be even more effective. Even if you’ve already started the course of antibiotics, it’s not too late to start taking probiotics to reduce any side-effects. Always remember to complete taking the course of antibiotics as prescribed.

 

 

Putting all of this together to answer the initial question of whether it’s better to take probiotics or prebiotics, a better answer may in fact be take both to cover the different effects each has, maximising the benefit to health. There are specific times when probiotics are better, and other times when prebiotics are better, and consuming both together may make each more effective. In any case care has to be taken to consume a product that has been confirmed through robust studies to have the specific benefit that is required.

 

Do polyphenols qualify as prebiotics? The latest scientific perspectives

Kristina Campbell, Consulting Communications Director, ISAPP

When the ISAPP scientific consensus definition of ‘prebiotic’ was published in 2017, the co-authors on the paper included polyphenols as potential prebiotic substances. At the time, the available data on the effect of polyphenols on the gut microbiota were insufficient to show a true prebiotic effect.

An ISAPP webinar held in April 2022, aimed to give an update on the health effects of polyphenols and their mechanisms of action, along with how well polyphenols fit the prebiotic definition. Prof. Daniele Del Rio from University of Parma, Italy, and Prof. Yves Desjardins from Université Laval, Canada, presented the latest perspectives in the field.

What are polyphenols?

Polyphenols are a group of compounds found in plants, with over 6000 types identified to date. They can be divided into two main categories, flavonoids and non-flavonoids.

Polyphenols are absorbed in two different ways in the body. A very small fraction is absorbed in the small intestine, but 95% of them reach the lower gut and interact with gut microbiota. Although polyphenols have a special capacity to influence the activities of microorganisms, some resident microorganisms, in turn, can change the chemical structure of polyphenols through enzymatic action. These interactions produce a unique array of metabolites, which may be responsible for some of polyphenols’ prebiotic effects.

What are the health effects of polyphenols?

Epidemiological studies show that polyphenols in the diet are associated with many health benefits, including prevention of cardiovascular disease, certain cancers, and metabolic disease. These effects occur through various mechanisms. However, association is not proof of causation. So how good is the evidence that polyphenols can lead to health benefits?

Numerous human studies exist, but the most robust study to date for the health benefits of polyphenols is a randomized, controlled trial of over 20,000 adults, published in 2022, which showed supplementation with cocoa extract reduced death from cardiovascular events (although it did not reduce the number of cardiovascular events).

What are the mechanisms of action for polyphenols?

Polyphenols have multiple mechanisms of action. Del Rio focuses on the metabolites produced from dietary polyphenols called flavan-3-ols, which are found in red wine, grapes, tea, berries, chocolate and other foods. Along with colleagues, he showed that the metabolites produced in response to a polyphenol-rich food occur two ‘waves’: a small wave in the first 2 hours after ingestion, and a larger wave 5-35 hours after ingestion. The second wave is produced when flavan-3-ols reach the colon and interact with gut microbiota.

Work is ongoing to link these metabolites to specific health effects. Along these lines, Del Rio described a study showing how cranberry flavan-3-ol metabolites help defend against infectious Escherichia coli in a model system of bladder epithelial cells. These polyphenols are transformed by the gut microbiota into smaller compounds that are absorbed—so the health benefit comes not from the activity of polyphenols directly, but from the molecule(s) that the gut microbiota has produced from the polyphenols.

How else do polyphenols work? Ample evidence suggests polyphenols interact in different ways with gut microbes: they have direct antimicrobial effects, they affect quorum sensing, they compete with bacteria for some minerals, and/or they modify ecology, thereby affecting biofilm formation. Desjardins explained that these interactions may occur in parallel: for example, polyphenols may exert antimicrobial effects when they reach the colon, and at the same time, microorganisms in the gut begin to degrade them.

The mode of action of polyphenols Desjardins studies is the prebiotic mode of action—or as he describes it, “prebiotic with a twist”. A landmark paper from 2015 showed how cranberry polyphenols had protective effects on metabolism and obesity through the creation of mucin in the intestine, which formed a good niche for Akkermansia muciniphila, a keystone bacterial species for good metabolic health. Other polyphenols have since been shown to work the same way: by stimulating production of mucin, thereby providing ideal conditions for beneficial bacteria to grow. In this way, polyphenols appear to show small-scale effects comparable to the effects of probiotics, by inducing a host response that alters the bacterial niche.

Are the effects of polyphenols individual?

Del Rio offered some evidence that the health effects of polyphenols, via metabolites, is personalized: a study showed the existence of three distinct patterns of metabolite production in response to dietary polyphenols (ellagitannins). These may depend on the particular microbes of the gut and their ability to produce the relevant metabolites—so in essence, in each case the gut microbiota is equipped to produce a certain set of metabolites in response to polyphenols. More work is needed, however, to be able to personalize polyphenol intake.

Do polyphenols qualify as prebiotic substances?

Polyphenols clearly interact with gut microbiota to influence human health. The definition of a prebiotic is “a substrate that is selectively utilized by host microorganisms conferring a health benefit”. Given the available evidence that polyphenols are not metabolized or utilized by bacteria in all cases in the same direct way as carbohydrate prebiotics, Desjardins sees them as having a “prebiotic-like effect”. Rather, polyphenols are transformed into other biologically active molecules that ultimately provide health benefits to the host. These prebiotic-like properties of polyphenols are nicely summarized in a 2021 review paper and include decreasing inflammation, increasing bacteriocins and defensins, increasing gut barrier function (thereby reducing low-grade inflammation), modulating bile acids, and increasing gut immuno-globulins.

Overall, the speakers showed that polyphenols exert their health effects in several ways—and while the gut microbiota are important for their health effects, polyphenols, as a heterogenous group, may not strictly meet the criteria for prebiotics. Clearly, more research on polyphenols may reveal other mechanisms by which these important nutrients influence the gut microbiome and contribute to host health, and they may someday be regarded as prebiotics.

Watch the replay of the ISAPP webinar here.

Decoding a Probiotic Product Label

By Mary Ellen Sanders, PhD

Interested in knowing what’s in your probiotic product? Unfortunately, there are many ways that probiotic product labels can fall short.

First, not all items labeled as “probiotic” truly meet the scientific criteria for a probiotic product. See here for information on what qualifies as a probiotic. Some fermented foods are marketed today claiming to be ‘probiotic’. But these products often have undefined microbial content and lack any studies documenting health effects, criteria that are required for a probiotic. Instead, such products could legitimately be labeled as containing ‘live, active cultures’. Dietary supplement products formulated with untested microbes should similarly not be labeled as probiotics.

Also, a label might not provide adequate information on what types of microbes are contained in the product. Genus and species may be listed, but no strain designation. Maybe only “bifidobacteria” or “lactobacilli” are listed.

They might not disclose the potency of individual strains in the product. Some may provide a total count of colony forming units (cfu)/dose or serving, which in the case of a single strain product is informative. But in the case of a multi-strain product – products may contain a couple or up to 30 strains – you don’t know if equal amounts of all strains are included, or perhaps the bulk of the count is made up of the strain in the formulation that is least expensive to manufacture rather than the one that will make the probiotic more effective. Some products may provide one count for “Lactobacillus” and another count for “Bifidobacterium”, a slightly more informative approach than just total count, but still lacking in detail. Many challenges exist for multi-strain products, including the lack of robust methods to quantify different strains once combined, especially viable ones. This topic was one that was covered in an ISAPP webinar, Current issues in probiotic quality: An update for industry.

The label may state that the count is “at time of manufacture”, a number that is no doubt inadequate if you purchase the product close to the end of its shelf-life. Most probiotic strains suffer cell count decline over the course of shelf-life, with some strains more susceptible than others. This situation almost guarantees that by the pull-by date for a multi-strain product, the ratio of cfu of strains to each other is likely much different than at the time of formulation.

Surveys of probiotic product labels

Additionally, it is difficult for consumers to know what products are backed by studies documenting a health benefit. If a product is not labeled sufficiently, it is impossible to link it to evidence. Two studies surveyed commercial probiotic products in the Washington DC area, Retail Refrigerated Probiotic Foods and Their Association with Evidence of Health Benefits and More Information Needed on Probiotic Supplement Product Labels. Results showed that 45% of retail dietary supplement products did not provide strain designations and an equal number did not provide a measure of potency through the end of shelf-life. Only 35% of products could be linked (based on strain and dose) to evidence of a health benefit. Food products fared a bit better, with 49% of refrigerated probiotic food products being linked to evidence of a health benefit. One clear indication from this study was that if your food product discloses the strain designation, it is likely to have evidence of a health benefit. An overall conclusion was that product labeling – at least in this region – needs improvement.

Historical context on guidelines for probiotic product labels

According to the FAO/WHO 2002 Working Group on Guidelines for the Evaluation of Probiotics in Food (page 39 of this combined document), the following information should be on probiotic labels:

– Genus, species and strain designation for each probiotic strain in the product.

– Minimum viable numbers of each probiotic strain at the end of the shelf-life, typically expressed in colony forming units (or cfu).

– The suggested serving size (or dose) must deliver the effective dose of probiotics related to any health benefit communicated on the label.

– Health claim(s) (as allowed by law and substantiated by studies)

– Proper storage conditions

– Corporate contact details for consumer information

These principles are developed and reiterated in “Best Practices Guidelines for Probiotics” (2017) developed by the Council for Responsible Nutrition and IPA.

Additional information

ISAPP created an infographic to explain the information on a probiotic labels. Our example portrays an imaginary dietary supplement for sale in the United States. Labels on foods containing a probiotic or a probiotic produced in another country would be labeled differently from this example to comply with applicable regulations. For those interested in probiotic labels in the EU, see the infographic ISAPP created for a probiotic product in the European Union. Also of interest, USP.org created an infographic on “How to Read a Dietary Supplement Label” for U.S. products.

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 board members give a scientific overview of synbiotics in webinar

Many kinds of products are labeled as synbiotics – but how do they differ from each other? And do they all meet the scientific criteria for synbiotic ingredients?

To demystify the science of synbiotics – including ISAPP’s definition published in 2020 – ISAPP is holding a free webinar: Synbiotics: Definitions, Characterization, and Assessment. Two ISAPP board members, Profs. Bob Hutkins and Kelly Swanson, present on the implications of the synbiotic definition for science and industry. They clarify the difference between ‘complementary’ and ‘synergistic’ synbiotics and cover the basics of meeting the criteria for synbiotic efficacy and safety. One challenge is learning when a synbiotic is required to have demonstrated both selective utilization of the microbiota in the same study that measures the health outcome. A Q&A is scheduled for the last 20 minutes of the webinar.

This webinar is for scientists, members of the public, and media who want a scientific overview on synbiotics as they appear in more and more consumer products.

The live webinar was broadcast on Friday, January 28th, 2022, from 10:00 am – 11:10 New York (Eastern) time.

Find the webinar recording here.

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.

Do antibiotics ‘wipe out’ your gut bacteria?

By Dr. Karen Scott, University of Aberdeen, UK

Antibiotics have been an important tool in medicine to kill pathogenic bacteria and treat infectious diseases for many decades. But for most of those decades, scientists had limited awareness of the community of ‘good’ microbes that reside in our guts and other parts of the body. Now that we have ample evidence of the beneficial functions of these abundant resident microbial communities, we need to be aware of the potential impact antibiotics may have on them – and whether antibiotics might wipe them out, creating a different health problem.

Antibiotics act against basic cellular functions of microbes – targeting cell wall synthesis, DNA/RNA synthesis, protein synthesis and folate synthesis. In order to avoid the effects of the antibiotics, bacteria can either alter their own target molecule so that the antibiotic is ineffective, actively pump the antibiotic out of the cell, or inactivate the antibiotic. With bacteria constantly trying to survive in the face of antibiotics, we are in a continuous race to ensure that the disease-causing bacteria we are trying to eliminate remain susceptible to the antibiotics used to treat them.

The action of antibiotics against bacteria can be classified according to:

  • Bacteriostatic (inhibiting growth of the target microorganism) vs. bactericidal (killing cells)
  • Narrow spectrum (acting against a few specific bacteria) vs. broad spectrum (acting indiscriminately against many bacteria).

Clearly an ‘ideal’ antibiotic would be narrow spectrum and bactericidal, rapidly killing only the target bacteria. In contrast a broad spectrum, bacteriostatic antibiotic may only inhibit growth of the target bacterium and at the same time may be bactericidal to others.

And here we come to the basic problem of antibiotic use in general medicine. When a patient attends the doctor’s office with a complaint such as a sore throat or an ear infection, most likely due to a viral infection, the doctor has a few choices:

  1. The doctor can inform the patient that antibiotics would be ineffective, and that the infection will go away by itself in a few days, and that the patient go home, rest and take other remedies to target symptoms such as pain, fever, or congestion in the meantime.
  2. The doctor can succumb to pressure from the patient demanding a prescription ‘remedy’ and prescribe an unnecessary and useless course of antibiotics. While this was common in the past, in many countries doctors now stand firm, maintaining antibiotics would be ineffective and are not required.
  3. The doctor can offer a delayed antibiotic prescription – sending the patient away with a prescription but advising the patient to wait for a couple of days to see if symptoms resolve before deciding if the prescription is required. This approach is becoming more common and does reduce unnecessary antibiotic use.
  4. Finally, the doctor can determine that even if the original illness was caused by a virus, there is now a secondary bacterial infection and that a course of antibiotics is now required. The problem here is that without a laboratory test the doctor cannot be sure which bacterium is causing the disease so in order to be sure that the antibiotic will be effective, a broad spectrum antibiotic is often prescribed.

Any antibiotic prescription that the patient collects from the chemist (pharmacist) and starts taking, immediately causes collateral damage to their own resident microbiota. It is now well-established that a short course of antibiotics disrupts the gut bacterial community, killing many important resident bacteria. This can be observed by a reduction in diversity (see articles here and here, and figure here), meaning that fewer different bacterial groups can be detected. Normally once the patient stops taking the antibiotic the diversity of the community increases within a month, almost returning to the starting composition. Almost. Some bacterial species are particularly sensitive to certain antibiotics and may never recover. Oxalobacter formigenes, the bacterium that protects against kidney stone formation, is one example.

The other hidden effect of antibiotic treatment is that although all members of the microbial community may re-establish, they may not be the same as before. The levels of antibiotic resistance amongst bacteria isolated from samples from patients after seven days of antibiotic treatment were much higher than those from controls without any treatment, even four years later (see here). The selection pressure exerted on bacteria during short courses of antibiotic treatment results in transfer of antibiotic resistance genes, and the spread of resistance to many other members of the microbial community, increasing the overall resistance profile. Whilst this may not be immediately damaging to the health of the person, this change in baseline resistance does mean that a subsequent course of antibiotic treatment could be less successful because more bacteria will be able to withstand being affected by the antibiotic, and more bacteria will contain resistance genes that could be transferred to disease-causing bacterium.

Historically, as soon as we started using purified antimicrobials therapeutically, we started seeing rise of resistance to those antibiotics. The first recognised tetracycline resistance gene, otrA, was identified in Streptomyces, a genus of Gram-positive bacteria now known to produce many antimicrobial agents as secondary metabolites (see figure here).

The indiscriminate effects of antibiotics can be even more severe in hospitalised patients. Recurring Clostridioides difficile-associated diarrhoea (CDAD) is a direct consequence of antibiotic treatment. The microbial diversity decreases in patients receiving antibiotics for legitimate therapeutic reasons, and the Clostridioides difficile population expands to occupy empty niches. Overgrowth of C. difficile results in toxin production, abdominal pain, fever and ultimately CDAD. Treatment is difficult because some C. difficile strains are antibiotic resistant and C. difficile forms non-growing spores that persist during the antibiotic treatment. This means that even if the initial infection is successfully treated, once the antibiotic treatment ceases the spores can germinate and cause recurring C. difficile infections. Although initial treatment with antibiotics works for 75% of patients, the remaining 25% end up with recurring CDAD infections. A more effective treatment may be faecal microbial transplant (FMT) therapy (see blog post here).

Scientists have spent the last 20 years investigating the many ‘good microbes’ that inhabit our intestinal tracts leading to a much greater understanding of what they do, and the potential repercussions when we destroy them. This means we are now very aware of the collateral damage a course of antibiotics can have. A new era of developing the ‘good microbes’ themselves as therapeutic agents, using them to treat disease, or to recolonise damaged intestinal ecosystems, beckons. New drugs may take the form of next generation probiotics or whole microbial community faecal transplants, or even postbiotics, but the common feature is that they are derived from the abundance of our important natural gut inhabitants.

 

What do we mean by ‘conferring a health benefit on the host’?

By Prof. Colin Hill, University College Cork, Ireland

Four of the Consensus definitions produced by ISAPP in recent years (see 1-4 below) finish with a similar wording, insisting that probiotics, prebiotics, synbiotics and postbiotics must confer a health benefit on the host”. This proviso was included to explicitly reinforce the fact that the raison d’etre for these interventions is that they must demonstrably improve host health. It would perhaps be wise to just stop there and leave the interpretation of what this really means to each individual reader. But that would not make for a very long blog and I am not very wise. Furthermore, it is useful to be more precise for scientific and regulatory purposes. At least two aspects seem to be open to elaboration; what is meant by ‘host’ and what is a ‘health benefit’? I will base my thoughts on the probiotic definition, but the logic should apply equally to all four health-based definitions.

Host. According to the Google dictionary a host is an animal or plant on or in which a parasite or commensal organism lives’. This means there are millions of potential host species on our planet, something that could potentially create confusion. For example, if a well characterised microbe (or microbes) is shown to provide a measurable health benefit when administered in adequate amounts in a murine model (the host) then it clearly meets the stated definition of probiotic. But only for mice! It should not be referred to as a probiotic for other species, including humans, solely based on murine evidence. This creates a situation where the same microbe can clearly meet the criteria to be a probiotic for one host but not for another. This is not simply semantics; it is of vital importance that it should not be assumed that health benefits confirmed in one host will also be realised in another without supporting evidence. Since the majority of discussions of probiotics address human applications, it may serve all stakeholders well – even if not directly mandated by the definition – if the word ‘probiotic’ was only used without qualification for microbes with measurable benefits in humans while all others should be qualified with the target host; ‘equine probiotic’, ‘canine probiotic’, or even ‘plant probiotic’.

Health benefit. Health is of course a continuum from a desirable but almost certainly unattainable state where every organ is performing optimally (something I will term ‘ideal health’) to a point where death is imminent (that I will term ‘poor health’). Of course, health is multidimensional and far more complex than a straight line between ‘ideal’ and ‘poor’ but for simplicity I will treat it as such. If we place ideal health on the left end of our straight line and poor health at the right end, then obviously any shift towards the left can be considered a health benefit. It could even be reasonably argued that if someone is gradually progressing from left to right down our imaginary line (for example, as we age) then halting or slowing down that progression could also be considered a health benefit. From this perspective every individual (not just the unwell) could potentially derive a health benefit from a probiotic, prebiotic, synbiotic or postbiotic.

The issue of cosmetic benefits is more nuanced. If an intervention improves someone’s appearance (or reduces body odour for example) it might not be considered a health benefit per se, but of course it could well have a beneficial effect on an individuals’ mental health. I will leave it to the psychologists and psychiatrists to determine how this could be convincingly demonstrated.

There is also the issue of production characteristics where the host is a food animal or a crop. If a microbial-based intervention leads to faster growth rates and increased yields should this qualify as a health benefit? My own opinion is if the intervention leads to higher productivity by preventing infections it could be considered a health benefit, but not if it simply leads to faster growth rates by improving feed conversion for example.

Can changing the microbiome be considered a health benefit? A trickier question is whether a direct effect on the microbiome could be considered as a health benefit? Every host has a microbiome of a particular configuration, richness, and diversity. I don’t think we are yet at a point where measurable changes in these general indices of microbiome composition can be termed a health benefit in the absence of a link to a more established health outcome. The consequence of any change will be microbiome-specific in any event; a reduction in diversity in the vaginal microbiome might be desirable, whereas an increase in diversity in the gut microbiome might well be considered beneficial. But what if we can measure a reproducible reduction in a specific pathobiont like Clostridioides difficile, or an increase in a microbe that is associated with good health such as Bifidobacterium? In my opinion we are arriving at a point where we can begin to refer to these impacts as a health benefit. This will become more and more relevant as we establish direct causal links between individual commensal microbes and health outcomes. Equally, an intervention that preserves microbiome structure during a disruption (e.g. infection or antibiotic treatment) could also be considered as beneficial. I don’t know if regulators are yet at the point of accepting outcomes such as these as direct health benefits, but I believe a strong case can be made.

To finish, I believe that it is a very exciting time for all of us in the field of probiotics, prebiotics, synbiotics and postbiotics, but it is really important that all of this important science is not compromised by loose language or by literal interpretations that adhere to the letter of the definitions but not to the intent. If you want to fully understand the intent of the definitions, I encourage you to read the full text of the consensus papers.

 

  1. https://doi.org/10.1038/nrgastro.2014.66
  2. https://doi.org/10.1038/nrgastro.2017.75
  3. https://doi.org/10.1038/s41575-020-0344-2
  4. https://doi.org/10.1038/s41575-021-00440-6

Children and dogs in a household share gut microbes – and these microbes are modified by a canine probiotic

From longtime family pets to ‘pandemic puppies’, dog ownership is seemingly more popular than ever. In households with children, scientists have found that a pet dog is one of the environmental factors that influences the gut microbiota in early life – but can the microbes that children and dogs share be modified?

A new study from ISAPP president Prof. Seppo Salminen (University of Turku, Finland) and colleagues recently explored the impact of a household dog on children’s gut microbiota, before and after the dogs were given a canine probiotic. Not only did the gut microbiota of dogs and children in the same household share features in common, but also the gut microbes of both shifted after dogs received a probiotic.

The study, which was part of a larger investigation, looked at families with at least one member who had allergic disease. Thirty-one of the families in the current study had dogs, and 18 families (the control group) did not. From each household, the fecal microbiota of one child (aged 5 or under) was tested. The fecal microbiota of the dogs was tested, and further, they received either a probiotic containing 3 canine-derived strains, or placebo.

The data supported previous observations that dogs and children share gut microbes: the children living with dogs had a distinct fecal microbiota composition. The most striking microbiota differences were a higher abundance of Bacteroides and short-chain fatty acid producing bacteria.

Moreover, when the household dogs were given a probiotic, both the dogs and the children living with them showed a gut microbiota shift, with a reduction in Bacteroides. (The exact probiotic strains were not tracked in the feces of either the dogs or the children.)

Were the changes beneficial? It’s not certain, since health outcomes in the children were not part of the study. But these findings provide more evidence for the effect of home environments and pets on the gut microbiota of children, and highlight the modifiability of both the dog’s and children’s gut microbiota. The ability to modify a child’s gut microbiota is of particular interest in the early years, when gut microbiota / immune interactions have the potential to shape health through the lifespan.

The study authors conclude, “Our promising data invite the idea that the compositional development of the gut microbiota in children is potentially modifiable by indirect changes in household pets and justify the further search of novel modes of intervention during critical period when the scene is set for the consolidation of the child later health.”

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)

 

The Microbiome — Can it aid in the diagnosis and therapy of irritable bowel syndrome (IBS)?

By Eamonn M M Quigley, MD FRCP FACP MACG FRCPI MWGO

Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders and seems to be prevalent across the globe1. Although non-fatal, IBS impacts on quality of life, personal relationships and productivity and can impose a significant socioeconomic burden on the individual as well as on society at large. Despite considerable effort there is still no test to diagnose IBS and, in clinical practice, the diagnosis commonly rests on the presence of characteristic symptoms, such as those defined by the Rome criteria2, in an individual in which alternate diagnoses have been excluded or deemed unlikely. The concern of the IBS sufferer and his/her physician is that because IBS symptoms are relatively non-specific (abdominal pain, altered bowel habit and bloating) a diagnosis based on symptoms alone may miss “something serious”.

Several challenges confront those who attempt to design a diagnostic test or new therapy for IBS. First, IBS is not a homogeneous disorder; symptoms, their severity and impact vary considerably. Second, symptoms tend to fluctuate over time with periods of calm interposed between episodes of much distress. Third, it is almost certain that IBS is multifactorial with various factors contributing to a variable extent in each sufferer. Over the years, genetic predisposition, gut motility and sensation, how the brain senses activity in the gut, and how the body responds to stress have all been invoked to explain the development of symptoms in IBS. While all of these factors undoubtedly contribute, none has yielded a diagnostic test.

One concept, that of the gut-brain axis, has served as a useful paradigm to explain IBS symptoms with dysfunction at various points along the axis, which extends all the way from the cerebral cortex to gut muscle, nerve and mucosa and back again, variably contributing to the presentation of IBS in different individuals3,4. Now, connections between the gut and the brain have been extended to include a new participant, the microbiome. This leads to the concept of the microbiome-gut-brain axis, whereby bacteria resident in the gut could impact on the “big brain” and even contribute to neurological and neuropsychiatric disease5. There is substantial experimental data to indicate that gut microbes influence components of the gut barrier, the intestinal immune system and the neuromuscular apparatus of the gastrointestinal tract, as well as central nervous system structure and function6.

Could the gut microbiome produce a diagnostic test for IBS?

That microbiota might be a factor in IBS was first suggested by the observation that IBS could develop de novo in the aftermath of acute enteric bacterial, viral or parasitic infections7. More recently, modern sequencing technology has been applied to fecal and colonic microbiota in IBS with the aim of determining relationships between a variety of clinical and demographic parameters and microbiota. Although data remain limited, and not always consistent, it is evident that IBS patients have an altered fecal microbiota relative to healthy individuals8. Currently available data are fraught with challenges in interpretation – small study populations, variations in patient selection and methodology, not to mention a failure to account for such confounders as diet, stool form and consistency, therapy, co-morbid psychopathology and symptom severity. Nonetheless, some overall patterns have emerged: the fecal and colonic mucosal microbiota are different in IBS and the fecal microbiota may not only predict severity9, but also responsiveness to one common intervention – the low fermentable oligo-, di- and monosaccharides and polyols (FODMAP) diet10. It is now abundantly clear that the expectation that a single microbial signature might typify IBS was naïve.

Recent progress

While we are not yet able to diagnose IBS using the microbiome, some very interesting observations have resulted from applying the highest quality microbiome science to what was once regarded as fringe and unimportant.

  1. Lessons from multi-omics

In the first of these studies, Kashyap’s lab, and its collaborators, employed a multi-omics approach in a longitudinal study of a reasonably large cohort of IBS sufferers and were able to identify IBS subtype-specific and symptom-related variations in microbial composition and function and to relate certain bacterial metabolites with physiological mechanisms relevant to IBS in the host11. A disturbed microbiome or an aberrant host response to the microbiome might well involve the generation of intraluminal molecules with biological effects on motility, sensation, gut barrier function, immune activation and, of course, communication with the central nervous system. A very high level of methodological complexity was needed to identify these relationships since IBS symptoms vary not only between individuals but over time within individuals.

  1. Food-related symptoms – linking bacteria, food antigens and the immune response

IBS sufferers have been telling us for decades that having a meal often makes their symptoms worse. Various explanations have been advanced to explain this phenomenon ranging from an exaggerated gastro-colonic reflex to food allergy and intolerance. A recent paper from Aguilera-Lizarraga and colleagues reveals just how complicated this story might well be – involving an interaction between bacterial infection, dietary antigens and immunoglobulin (Ig)E and mast cell responses in the host. In a mouse model, infection with Citrobacter rodentium led to a breakdown in oral tolerance to the food antigen ovalbumin which resulted in the development of an IgE antibody-mediated response locally in the colon and ultimately to diarrhea and visceral hypersensitivity, a common feature of IBS12. They went on to show that the injection of some common food antigens (soy, wheat, gluten and milk) into the rectosigmoid mucosa of IBS sufferers resulted in edema and mast cell activation. It was notable that the development of visceral hypersensitivity in the mouse model did not appear to be related to any change in the resident microbiome or to ongoing chronic inflammation but seemed to be a very specific interaction between the original infectious insult, loss of oral tolerance and the subsequent development of IgE antibodies to a dietary antigen. The net result was the activation of neural pathways responsible for visceral hypersensitivity.  These findings certainly extend our understanding of post-infection IBS, but to what extent they relate to IBS, in general, remains to be determined.

  1. Beyond bacteria

To date the focus on studies of the microbiome in IBS (or, for that matter, in most disease entities) has been on bacteria. Das and colleagues expanded their microbiota inquiry to consider the contributions of fungi (the mycobiome) to IBS13. They found significant differences in mycobiome diversity between IBS sufferers and control subjects but the mycobiome could not differentiate between IBS subtypes. Interestingly, mycobiome alterations co-varied with those in the bacteriome but not with dietary habits. Unfortunately, as has been the case with studies of bacterial populations, these changes in the mycobiome proved “insufficient for clinical diagnosis”.

  1. Fecal microbiota transplantation and IBS

Based on the assumption that gut microbial communities are disturbed in IBS and considering the success and overall excellent safety record of fecal microbiota transplantation/transfer (FMT) in the management of severe or recurrent Clostridioides difficile infection, it should come as no surprise that FMT has been employed in IBS14-24. Results to date have been mixed and, for now, preclude a recommendation that FMT be adopted to treat IBS. Two observations are of note. Both are derived from a randomized double-blind, placebo-controlled, clinical trials where the instillation of the patient’s own feces served as the control. First, the positive clinical results in the studies by El-Salhy and his colleagues seem to relate to the use of a “super-donor”20. Second, the report from Holvoet and colleagues suggests that the baseline microbiome of the recipient predicted response to FMT albeit in a very unique group of IBS sufferers21.  Indeed, it appears that a successful FMT, in IBS, is associated with the normalization of a number of components of the colonic luminal milieu22-24. Herein may lie clues to guide the future use of “bacteriotherapy” in IBS.

Conclusions 

It should come as no surprise, given advances in techniques to study the microbiota coupled with exciting data from animal models, that the paradigm of the microbiota-gut-brain axis has been proposed as relevant to IBS. The possibility that a disturbed microbiome, or an aberrant host-response to that same microbiome, might be relevant to IBS and could impact on the CNS is now being contemplated seriously as an avenue to understand disease progression and treatment as well as to open new diagnostic and therapeutic possibilities on this challenging disorder. As much of the extant data comes from animal models one must remain cautious in their interpretation – no single animal model can recapitulate the IBS phenotype. The bi-directionality of microbiota-gut-brain interactions must also be remembered – the complex interactions between inflammation and the gut microbiota exemplify how a disease state can impact on the microbiota.  With regard to interventions, there are many intriguing approaches, but still a long way to go to achieve personalized pharmabiotic therapy for that very special individual – the IBS sufferer.

References

  1. Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology 2020 [epub ahead of print].
  2. Lacy BE, Mearin F, Change L, et al. Bowel Disorders. Gastroenterology 2016;150:1393-1407.
  3. Camilleri M, Di Lorenzo C. Brain-gut axis: from basic understanding to treatment of IBS and related disorders. J Pediatr Gastroenterol Nutr. 2012;54:446-53.
  4. Camilleri M. Physiological underpinnings of irritable bowel syndrome: neurohormonal mechanisms. J Physiol. 2014;592:2967-80.
  5. Quigley EMM. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases. Curr Neurol Neurosci Rep 2017;17:94.
  6. Mayer EA, Tillisch K, Gupta A. Gut-brain axis and the microbiota. J Clin Invest. 2015;125:926-38.
  7. Klem F, Wadhwa A, Prokop LJ, et al. Prevalence, Risk Factors, and Outcomes of Irritable Bowel Syndrome After Infectious Enteritis: A Systematic Review and Meta-analysis. Gastroenterology. 2017;152:1042-1054.
  8. Pittayanon R, Lau JT, Yuan Y, et al. Gut Microbiota in Patients WithIrritable Bowel Syndrome-A Systematic Review. 2019;157:97-108.
  9. Tap J, Derrien M, Törnblom H, et al. Identification of an Intestinal Microbiota Signature Associated With Severity of Irritable Bowel Syndrome. Gastroenterology. 2017;152:111-123.
  10. Bennet SMP, Böhn L, Störsrud S, et al. Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs. Gut 2018;67:872-81.
  11. Mars RAT, Yang Y, Ward T, et al. Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome. 2020;183:1137-1140.
  12. Aguilera-Lizarraga J, FlorensMV, Viola MF, et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature 2021;590:151-156.
  13. Das A, O’Herlihy E, Shanahan F, et al. The fecal mycobiome in patients with Irritable Bowel Syndrome. Sci Rep 2021;11:124.
  14. Myneedu K, Deoker A, Schmulson MJ, Bashashati M. Fecal microbiota transplantation in irritable bowel syndrome: A systematic review and meta-analysis. United European Gastroenterol J. 2019;7:1033-1041.
  15. Halkjær SI, Christensen AH, Lo BZS, et al. Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study. 2018;67:2107-2115.
  16. Johnsen PH, Hilpüsch F, Cavanagh JP, et al.Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. Lancet Gastroenterol Hepatol. 2018;3:17-24.
  17. Aroniadis OC, Brandt LJ, Oneto C, et al. Faecalmicrobiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2019;4:675-685.
  18. Johnsen PH, Hilpüsch F, Valle PC, Goll R. The effect of fecal microbiota transplantation on IBS related quality of life and fatigue in moderate to severe non-constipated irritable bowel: Secondary endpoints of a double blind, randomized, placebo-controlled trial. 2020;51:102562.
  19. Lahtinen P, Jalanka J, Hartikainen A, et al. Randomised clinical trial: faecalmicrobiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel  Aliment Pharmacol Ther. 2020;51:1321-1331.
  20. El-Salhy M, Hatlebakk JG, Gilja OH, et al. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut. 2020;69:859-867.
  21. Holvoet T, Joossens M, Vázquez-Castellanos JF, et al. FecalMicrobiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial. 2021;160:145-157.
  22. Mazzawi T, Hausken T, Hov JR, et al. Clinical response tofecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels. Scand J Gastroenterol. 2019;54:690-699.
  23. Goll R, Johnsen PH, Hjerde E, et al. Effects offecal microbiota transplantation in subjects with irritable bowel syndrome are mirrored by changes in gut microbiome. Gut Microbes. 2020;12:1794263.
  24. El-Salhy M, Valeur J, Hausken T, Gunnar Hatlebakk J. Changes infecal short-chain fatty acids following fecal microbiota transplantation in patients with irritable bowel  Neurogastroenterol Motil. 2020:e13983.

 

ISAPP board members look back in time to respond to Benjamin Franklin’s suggestion on how to improve “natural discharges of wind from our bodies”

Benjamin Franklin, born in 1706, was a multi-talented politician and scientist best known for his discoveries related to electricity. Historians say he was scientifically pragmatic—aiming not just to advance theories, but to solve the most vexing problems of the day.

In 1780, when Franklin read about the intellectual contests being held by The Royal Academy of Brussels (today known as the Royal Flemish Academy of Belgium for Science and the Arts – KVAB), he took it upon himself to write an amusing letter that contained a suggestion for an important scientific challenge: “To discover some Drug wholesome & not disagreable, to be mix’d with our common Food, or Sauces, that shall render the natural Discharges of Wind from our Bodies, not only inoffensive, but agreable as Perfumes.”

Over two centuries later, the organization was prompted for a reply. Writer Brian Van Hooker wrote to the KVAB: ‘I am a writer at MEL Magazine and I am working on a piece about a letter that Benjamin Franklin sent to your organization’s predecessor, the Royal Academy of Brussels, 240 years ago. The letter was entitled “Fart Proudly,” and I’m reaching out to see if anyone at your organization might like to issue a reply to Mr. Franklin’s letter’.

Since ISAPP board member Prof. Sarah Lebeer (University of Antwerp, Belgium) is a KVAB Belgian Young Academy alumna with microbiome knowledge, Bert Seghers from the Academy asked her to help draft a reply. However, since the gut microbiome is not her main area of expertise, she consulted her fellow ISAPP board members. For example, Bob Hutkins, author of a popular ISAPP blog post on intestinal gas, immediately sent her a paper entitled Identification of gases responsible for the odour of human flatus and evaluation of a device purported to reduce this odour with the comment: “The next time a graduate student complains about their project, refer them to this paper and the 5th paragraph of the methods”—a paragraph that describes how scientists in the experiment were tasked with rating the odor of flatus and differentiating between the different smells of sulphur-containing gases.

But it was the answer of Prof. Glenn Gibson (University of Reading, UK) that was incorporated into the ‘formal’ reply to Franklin’s suggestion. “Your suggested topic on improving flatulence odour is amusing, but indeed also very relevant. An outstanding answer to the contest as you formulate it would be ground-breaking,” wrote Profs. Lebeer and Gibson. They noted that gases in the intestine are mainly released by the bacteria living there—but especially the sulphate reducing bacteria contribute to the “traditional” smell due to their production of noxious H2S —and that advances in probiotic and prebiotic science could one day lead to reduced (and “nicer smelling”) gas production by switching hydrogen gas production to methane or even acetate and away from H2S.

Brian Van Hooker summarized: “In other words, Mr. Franklin, they’re working on it and, perhaps sometime within the next 240 years, your dream of non-smelly farts might just come true.”

The KVAB response to Benjamin Franklin concluded: “Your letter is a ripple through time. It may not surprise you that scientific questions can have effects across decades and even centuries. This idea remains the tacit hope of many scientists working together for the progress of humanity. We have not yet invented a reverse time machine, but we send our answer along with your question forward in time, hoping that it may inspire future scientists as your question inspired us.”

Read the MEL Magazine article here.

Read more about gut microbiota & intestinal gas here.

ISAPP ha estado trabajando en colaboración con la Sociedad de Enterocolitis Necrotizante

La Asociación Científica Internacional para Probióticos y Prebióticos (ISAPP, por sus siglas en inglés), ha estado trabajando en colaboración con la Sociedad de Enterocolitis Necrotizante (NEC Society) en el desarrollo de una infografía sobre el rol de los probióticos en la prevención de la Enterocolitis Necrotizante (ECN).

La ECN es una enfermedad intestinal que puede poner en peligro la vida principalmente en bebés prematuros. Esta enfermedad produce un proceso inflamatorio que puede provocar daños en el tejido intestinal e incluso la muerte.

La leche materna de la madre del bebé es la forma más importante de ayudar a disminuir el riesgo de ECN. La leche pasteurizada de madres donantes es la segunda mejor opción. Adicionalmente, suministrar probióticos a bebés prematuros, junto con la leche materna, puede reducir el riesgo de ECN.

Los probióticos son microorganismos vivos que, cuando se administran en cantidades adecuadas, confieren un beneficio para la salud del huésped.

Los padres con hijos con riesgo de desarrollar ECN pueden consultar a los responsables de la Unidad de Cuidados Intensivos, sobre la posibilidad de utilizar probióticos para contribuir a prevenir el desarrollo de ECN.

ISAPP ha preparado una infografía en español con mayor información sobre este tema, la cual se puede encontrar aquí.

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.

 

The future is microbial: A post-pandemic focus on identifying microbes and metabolites that support health

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

The COVID-19 pandemic has been a sobering reminder of the significance that microorganisms have on human life. Despite the tremendous scientific and medical advances of the twentieth century, our best precautions against the virus have been to practice the oldest and most simplistic of all public health measures such as washing hands and maintaining physical distance from others. At the same time, the effectiveness of the new SARS-CoV-2 vaccines and the speed in which they were developed show how sophisticated and advanced our understanding of viruses has become. Taken together, the limitations and successes of responses to the pandemic underscore the power of investment in microbiology research. This research, which was first catalyzed by the pioneering work of Louis Pasteur, Robert Koch, and contemporaries in the late 1800s, was the basis for the overall reduction in infectious diseases during the twentieth century. Continued investment in these efforts will prepare us for the next pandemic threat.

Beyond pathogens to health-promoting microbes

As our attention turns to the promise of the New Year, we may also take this moment to appreciate the fact that microorganisms can also do good. Our “microbial friends” were first promoted by the lauded biologists Élie Metchnikoff, Henry Tissier, and Issac Kendall at the turn of the twentieth century. Since then, nearly another century passed before the power of microorganisms to benefit human health reached wider acceptance.

Marked by the emergence of laboratory culture-independent, nucleic-acid based methods to study microbial communities, there is now excitement in the identification of microorganisms that are important for health promotion. This interest is catalyzed by the urgency to find ways to prevent and treat cardiovascular diseases, cancers, and other non-communicable, chronic conditions that are now the leading causes of death worldwide. Much like the pressure to address infectious diseases as the primary cause of mortality prior to the twentieth century, so too is the need today for sustained research investments in studying how certain microorganisms contribute to, or may be essential for, preventing and treating the greatest threats to public health in the modern era.

Exemplified by the growing number of human microbiome studies, it is now broadly understood that the human microbiome contributes positively to digestive, immune, and endocrine systems function. Systematic reviews and meta-analyses of clinical trials support the use of probiotics for a variety of conditions and there are positive associations between the consumption of fermented dairy foods and good metabolic health. To understand how microbes can be beneficial, numerous mechanisms have been proposed (for example, modulation of the immune system and production of neurochemicals that can impact the gut-brain axis), and these mechanisms apply to both autochthonous microbiota and probiotics alike. However, our understanding of exactly how this occurs lags far behind what is currently known about microorganisms that cause harm.

Identifying microbes & metabolites that maintain health

The future of beneficial microbes is in identifying the specific, health-promoting metabolites, proteins, and other compounds that they make. Presently only a handful of such examples are known. Perhaps most recognized are the short chain fatty acids, butyrate, propionate, and acetate, which are known to bind specific human cell receptors to modulate numerous cell pathways including those that affect metabolism. Other microbial compounds generated as intermediate or end products of microbial metabolism (such as metabolites of amino acids), secondary metabolites (such as bacteriocins), and bacterial cell surface constituents (such as certain membrane proteins) were shown to benefit health, although a more complete description of mechanistic details for their effects remains to be discovered. Precise mechanistic descriptions of “beneficial factors”, or the microbial enzymatic pathways and molecules that induce desired cellular and systemic responses in the human body, will be pivotal for elucidation of the precise ways microorganisms sustain health and well-being (for more detail on this topic see here).

Based on what we know about the complexity of the human microbiome and the now many decades of probiotics research, this effort will require innovation and multi-disciplinary coordination. Just as early microbiologists raced to address the high rates of mortality due to microbial pathogens, we are in a new age where again microorganisms are regarded as emerging public health threats. However, we now have to our advantage the knowledge that not all microorganisms cause harm but instead the majority may offer solutions to the greatest health challenges of the twenty-first century.

 

 

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.

Ambient yogurts make a global impact

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

Quick, which country consumes the most yogurt? Must be France? Or the Netherlands? Maybe Turkey? The United States, perhaps? Try none of the above: the answer is China.

While many other countries consume way more yogurt than China on a per capita basis, China’s population gives it an advantage, with 1.4 billion potential consumers. And yogurt has become one of the most popular snack foods in China. It’s especially trendy among young and affluent urbanites. Indeed, total consumption of yogurt in China now exceeds that of France, the Netherlands, Turkey, and the United States, combined!

Whereas per capita consumption of yogurt in China in 2000 was around 1 kg per person per year, it’s now approaching 5 kg. Yogurt consumption even exceeds that of fluid milk.

Considering that dairy consumption was virtually non-existent in China for thousands of years, this trend is nothing short of a cultural phenomenon. While some of the yogurt consumed in the country is produced by domestic manufacturers, yogurt and yogurt ingredients are also being imported from other countries in the region, including New Zealand and Australia.

There is, however, one major difference between yogurt typically consumed in China and the products consumed in other regions. Indeed, ambient yogurt, short for “yogurt-based product for ambient distribution”, is all the rage in China.

Ambient yogurt and yogurt drink products, as the name implies, are stable at room temperature. This is achieved by heat-treating the yogurt after fermentation.  Many ambient yogurts are aseptically processed similar to ultra-high-temperature processed (UHT) products, leaving the product commercially sterile (i.e. without live microbes) and stable for up to a year. In China, these products can still be labeled as yogurt.

Not only are these ambient yogurt products convenient for retailers, but also, a cold-chain infrastructure, often absent in rural areas of China, is not necessary during transport and distribution. Perhaps for this reason, ambient yogurts are also being introduced in other regions, including Africa, South America, and the Middle East.

The popularity of yogurt in China, in the absence of a live microbe label declaration, is evidently due to the ‘healthy’ virtues or halo effect ascribed to yogurt, because of its high protein, calcium, and vitamin content. Perhaps there are also postbiotic benefits in the yogurt – this would be an interesting topic for research. But the novel flavors, textures and grab-and-go convenience, especially for drinkable yogurt products, also appeals to teens and young adults.

Traditionalists balk at the very idea of heat-treating yogurt and inactivating the live microorganisms. In some countries, such products cannot even be labeled as yogurt. In the U.S., these products can be labeled as yogurt but must be further labeled as “heat-treated”.

In reality, consumers’ expectation of live microbes in yogurt is so ingrained that heat-treated yogurts are nearly impossible to find in the United States. Indeed, yogurt, kefir, and other cultured milk and non-dairy products are promoted, in part, on the high number of viable microbes they contain. Probiotics are added to more than 90% of the yogurts sold in the United States.

According to international CODEX standards, yogurt must be made with Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus, AND must contain at least 107 CFU/g “through to the date of minimum durability after the product has been stored under the storage conditions specified in the labeling”. Any other labeled bacteria must be present at a minimum of 106 CFU/g. The CODEX standards have been widely adopted, although some countries have lower minimum levels.

Interestingly, and despite appeals by yogurt manufacturers, the U.S. Food and Drug Administration does not require minimum numbers of CFUs for yogurt. They have been considering changes that would be consistent with CODEX for more than a decade. In regions that do not require the CODEX standards, the International Dairy Foods Association offers the Live & Active Cultures (LAC) seal, which requires 107 CFU/g of yogurt cultures at time of manufacture.

The China National Food Safety Standard for Fermented Foods does specify a minimum Lactobacillus count of 106 CFU/g, but importantly, also includes the following footnote:

“products that have gone through heat treatment after the fermentation process will not be subjected to any requirements on the minimum Lactobacillus Count”

Such products, however, must be labeled as heat-treated. It should be noted that there is still a substantial market for more traditional (chilled) yogurt containing live microorganisms.  Still, ambient yogurts account for most of the yogurt consumed in China.

Given the relatively flat yogurt market in Europe and the United States, it should not be surprising that this rapidly growing market in China has attracted so much attention.  The China Nutrition Society and government policymakers have recommended that consumers increase dairy consumption to 3 times higher than current levels. That means a lot more yogurt will be consumed in China.

Translated, that means, from culture companies to processing and packaging industries, there will continue to be plenty of interest, innovation, and investment in yogurt for the Chinese population. For example, new generation yogurt products have recently been introduced with the claim of having 90 days’ shelf-life and containing live probiotic bacteria.

Still, whether by new or traditional technologies, the availability and consumption of live microbes in yogurt and other cultured products may be expected to increase as Chinese consumers become more informed about their health benefits. Perhaps, as cold-chain infrastructure also improves, these live yogurts may become a bigger part of the yogurt culture in China.

 

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

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

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

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

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

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

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

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

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

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

Read more about the efforts of the NEC Society here:

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

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

10 Things All Parents of NICU Babies Need to Know

9 Things You Need to Know About Necrotizing Enterocolitis

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

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

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

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

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

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

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

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

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

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

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

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

Prof. Maria Marco, PhD, University of California Davis

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

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

Prof. Bob Hutkins, PhD, University of Nebraska Lincoln

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

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

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

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

Prof. Dan Merenstein, MD, Georgetown University

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

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

Prof. Colin Hill, PhD, University College Cork

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

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

Prof. Dan Tancredi, PhD, University of California Davis

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

See ISAPP’s press release on this paper here.

Locally produced probiotic yogurt for better nutrition and health in Uganda

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

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

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

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

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

Further reading:

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

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

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

YOGURITO –the Argentinian social program with a special yogurt

 

 

 

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

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)