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Archive Highlight: New evidence on the virome in gut-brain communication and stress, with Nathaniel Ritz and Thomaz Bastiaanssen

/in Podcast, Season Three /by Laura

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Continuing our series on the microbiota-gut-brain axis, we are highlighting Episode 34 from our archives. In this episode, the ISAPP hosts discuss a new study on how the gut virome affects the host during stress, with Nathaniel (Nate) Ritz from the Institute for Systems Biology in Seattle, USA and Thomaz Bastiaanssen from APC Microbiome Ireland. The guests give an overview of the microbiota-gut-brain axis, then delve into a new study they led on the virome and its effects on stress responses in mice.

Key topics from this episode:

  • The gut and the brain communicate in various ways, and the microbiota play a role in some of these modes of communication. Various studies use animal models to look at mechanisms that might be applicable to humans.
  • Why would the microbiota affect the human brain? Because we evolved with a ‘background’ of microbes and have relied on them as we evolved. For example, gut microbes produce metabolites the human body is unable to produce by itself.
  • The newly published paper is titled “The gut virome is associated with stress-induced changes in behaviour and immune responses in mice”.
  • Most microbiota-gut-brain axis research to date has looked at the bacterial component of the microbiome, but this misses the bigger context. The virome is the collection of viruses in the gut, mostly consisting of bacteriophages (which infect bacteria in the gut). This study focused on the virome and how it influenced the gut bacteriome as well as host behavior.
  • Bioinformatics challenges exist when working with the virome for several reasons. For one, distinguishing the biology of a bacteriophage from its host can be challenging.
  • The study used a fecal virome transplant: taking a fecal sample, removing the cellular organisms and small particulates so that the bacteriophages were left over, and then concentrating them and administering them. The researchers took this entire virome from a mouse, then transferred it back to the same individual mouse while it was undergoing stress.
  • After stress, differences were seen in the mouse gut bacteriome and virome. The mice had higher anxiety- and depression-like behaviour, plus changes in their immune systems. But after the fecal virome transplant, some of their behaviours were improved.
  • Do the viruses impact the host nervous system directly, or do they only affect the host by way of the bacteriome? This is not fully known, but there appears to be very little interaction of the bacteriophages with the host. 
  • Analysis of the gut bacteriome or virome must respect the compositional nature of the data. The types of measurements used to analyze the microbiome and virome are confounded by compositional effects, and in the field this is not respected as much as it should be.
  • The next step after this study is to explore the changes in microbiome function in the mice, perhaps pinpointing which bacterial groups need to be changed to normalize the mouse behaviours.

Episode links:

About Nathaniel Ritz:

Dr. Nathaniel Ritz completed his PhD in Prof. John Cryan’s lab at APC Microbiome Ireland where he studied the role of the bacteriome and the virome in social and stress-related disorders. His interests lie in elucidating microbiota-host interactions and establishing microbiota causality within the microbiota-gut-brain axis. Nathaniel has recently moved to Seattle, Washington, USA, to join the lab of Dr. Sid Venkatesh as a postdoctoral fellow at the Institute for Systems Biology to further unravel the mechanisms underpinning microbe-host interaction. Outside of the lab, Nathaniel is an avid rock climber, dog walker, and partner to fellow scientist Dr. Minke Nota. More details and current position can be found at https://venkatesh.isbscience.org/

About Thomaz Bastiaanssen:

Dr. Thomaz Bastiaanssen is the lead bioinformatician in Prof. John F. Cryan’s microbiota-gut-brain axis group in Cork, Ireland. He is interested in the ecological dynamics governing host-microbe communication and how this complex interplay can impact human well-being. He will soon transition to a new role at Amsterdam UMC, the Netherlands, where he will continue to study the microbiome gut-brain axis. Besides working on multi-omics analyses, he enjoys horror stories, tabletop games and spending time with his wife, son, and corgi. His website can be found at: https://thomazbastiaanssen.github.io/

Archive Highlight: The role of microbes in gut-brain communication, with Prof. Emeran Mayer MD

/in Podcast, Season Three /by Laura

 

Podcast: Play in new window | Download

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Continuing our series on the microbiota-gut-brain axis, we are highlighting Episode 26 from our archives. In this episode, ISAPP podcast host Prof. Dan Tancredi PhD welcomes guest Prof. Emeran Mayer MD, a gastroenterologist and researcher at University of California Los Angeles. They talk about the microbiota-gut-brain axis, covering its evolutionary origins and how this complex system works in the human body to support overall health.

Key topics from this episode:

  • Microbiota-gut-brain communication has a long evolutionary history: microbes have been around for billions of years and they stored a lot of information in their genes. At some point in evolution microbes got inside the digestive tube of a primitive marine animal called hydra and it proved advantageous for this animal.
  • The hydra shows the origin of the human enteric nervous system (ENS): microbes live inside this tube and transfer genes to the nerve cells of this digestive tube, showing the origin of neurotransmitters.
  • Today in humans the neurotransmitters influence gene expression of microbes and change the microbial behaviors; the metabolites produced feed back to the brain.
  • Prof. Mayer’s initial interest as a gastroenterologist was the ENS and how it regulates motility. Subsequently the ENS was found to regulate many gut functions. The gut also houses a large part of the immune system and a complex hormonal system, and all these systems are connected with each other and communicate with the brain.
  • There is an increasing understanding that many chronic diseases relate to Inappropriate engagement of the immune system, starting in the gut.
  • When Prof. Mayer started in the field, the term “gut health” did not exist. Now it’s a ubiquitous term which has associations with wellbeing, acknowledging the gut has influence on many other body systems.
  • The associations between gut (microbiota) and brain health started with provocative animal experiments from Cork, Ireland, in which researchers manipulated the gut microbiome and found changes in emotion-like behaviors of animals. However, it has been difficult to translate to human interventions.
  • How do microbiome-targeted dietary interventions affect the brain? We do know the “Standard American Diet” (deficient in fiber) has changed the gut microbes in a way that compromises the production and maintenance of the gut barrier. 
  • There are many misconceptions about “leaky gut”, but basically contact between beneficial microbes and immune system sensors stimulate the immune system of the gut to low-grade inflammation. This can alter the tight junctions, making the gut more permeable, and ultimately this can affect the brain. Diet can affect the role of microbes in maintaining an effective gut barrier.
  • Prof. Mayer describes how he ended up studying the microbiota-gut-brain axis – he would not have predicted how important and popular this field would become.
  • In the future, there will be more sophisticated and personalized interventions. He sees a paradigm shift happening from reductionist approaches in medicine to systems biological approaches. This field is making us acknowledge that diet will play a major role.

Episode links:

About Prof. Emeran Mayer MD:

Emeran A Mayer is a Gastroenterologist, Neuroscientist and Distinguished Research Professor in the Department of Medicine at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress & Resilience and Founding Director of the Goodman Luskin Microbiome Center at UCLA. He is one of the pioneers and leading researchers in the bidirectional communication within the brain gut microbiome system with wide-ranging applications in intestinal and brain disorders. He has published 415 scientific papers, co edited 3 books and has an h-index of 125. He published the best selling books The Mind Gut Connection in 2016, the Gut Immune Connection in June 2021, and the recipe book Interconnected Plates in 2023. He is currently working on a MasterClass and a PBS documentary about the mind gut immune connection. He is the recipient of numerous awards, including the 2016 David McLean award from the American Psychosomatic Society and the 2017 Ismar Boas Medal from the German Society of Gastroenterology and Metabolic Disease.

Archive Highlight: Biotics in animal and human nutrition, with Prof. Kelly Swanson PhD

/in Podcast, Season Three /by Laura

 

Podcast: Play in new window | Download

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Completing our series on the role of biotics in animal health, we are highlighting Episode 22 from our archives. In this episode, Prof. Kelly Swanson PhD from University of Illinois at Urbana-Champaign discusses the role of biotics in animal and human nutrition. He reviews the criteria for prebiotics and synbiotics, then discusses how we gain knowledge about nutrition and the role of biotics in animals compared to humans.

Key topics from this episode:

  • A good argument can be made that biotics are essential for our diet; they are beneficial even if efficacy is sometimes difficult to prove.
  • Nutrients have an impact on the host’s health and simultaneously on the host-associated microbes.
  • Health benefits are essential to the FDA definition of fiber.
  • Antibiotics’ effect on the microbiota: short-term effects may be minor, but we still don’t know the long-term effects.
  • The synbiotics definition, criteria for products to meet this definition, and the health outcomes from using these biotic substances.
  • The difference between complementary and synergistic synbiotics.
  • When studying biotics in companion animals (cats and dogs), can results from one host be extrapolated to another host? Final studies should be in the target host.
  • Biotics are important in veterinary medicine and a popular topic of study.
  • Predictions about the future of nutrition science as informed by the microbiome.

Episode links:

Additional resources:

About Prof. Kelly Swanson:

Kelly Swanson is the Kraft Heinz Company Endowed Professor in Human Nutrition at the University of Illinois at Urbana-Champaign. His laboratory studies the effects of nutritional interventions, identifying how diet impacts host physiology and gut microbiota. His lab’s primary emphasis is on gastrointestinal health and obesity in dogs, cats, and humans. Much of his work has focused on dietary fibers and ‘biotics’. Kelly has trained over 40 graduate students and postdocs, published over 235 peer-reviewed manuscripts, and given over 150 invited lectures at scientific conferences. He is an active instructor, teaching 3-4 nutrition courses annually, and has been named to the university’s ‘List of Teachers Ranked as Excellent by Their Students’ 30 times. He serves on advisory boards for many companies in the human and pet food industries and non-profit organizations, including the Institute for the Advancement of Food and Nutrition Sciences and International Scientific Association for Probiotics and Prebiotics.

Targeting the rumen microbiota for reduced methane production, with Prof. Alex Hristov PhD

/in Podcast, Season Three /by Laura

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This episode features Prof. Alex Hristov PhD from Penn State University (USA) talking about the microbiota of ruminants and how it can be targeted for reduced methane production. The rumen (pre-stomach area) of cows and other animals contains microorganisms that digest the feed before it enters the rest of the gastrointestinal tract. Hydrogen is produced to inhibit further fermentation of the feed, and this hydrogen is rapidly converted to enteric methane, which is emitted by the animal – accounting for a large proportion of methane emissions that contribute to global warming. Several approaches exist for targeting the rumen microbiota with the aim of reducing methane emissions. Some feed additives, including one recently approved by regulators in the US, can reduce enteric methane by around 30% and appear safe for the animal. Vaccines against the methane-producing archaea in the rumen are another potential approach suitable for grazing livestock. Direct microbials have also been advanced. Many other sources of methane emissions exist besides livestock, but significantly reducing the methane production in the livestock industry could have a major positive impact on global warming. Feed additives for now are the leading strategy, and adoption of existing solutions in multiple places is critical. This episode is part of a series on the role of biotics in animal health.

Episode abbreviations and links:

Additional resources:

ISAPP blog post: Microbiota from a surprising source—baby kangaroos—might decrease cattle methane production

About Prof. Alex Hristov PhD:

Dr. Alexander N. Hristov is a Distinguished Professor of Dairy Nutrition in the Department of Animal Science at The Pennsylvania State University. He has a Ph.D. in Animal Nutrition from his native Bulgaria. Hristov has worked at the USDA-ARS Dairy Forage Research Center in Madison, WI, the Ag Canada Research Center in Lethbridge, AB, was on the faculty at the Department of Animal and Veterinary Science, University of Idaho from 1999 to 2008 and is at Penn State since 2008. Hristov’s main research interests are in the areas of mitigation of nutrient losses and gaseous emissions from dairy operations and protein and amino acid nutrition of dairy cattle. He has published over 220 peer-reviewed journal papers, books, and book chapters.

Episode 34: New evidence on the virome in gut-brain communication and stress, with Nathaniel Ritz and Thomaz Bastiaanssen

/in Podcast, Season Three /by Laura

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | RSS

In this episode, the ISAPP hosts discuss a new study on how the gut virome affects the host during stress, with Nathaniel (Nate) Ritz from the Institute for Systems Biology in Seattle, USA and Thomaz Bastiaanssen from APC Microbiome Ireland. The guests give an overview of the microbiota-gut-brain axis, then delve into a new study they led on the virome and its effects on stress responses in mice.

Key topics from this episode:

  • The gut and the brain communicate in various ways, and the microbiota play a role in some of these modes of communication. Various studies use animal models to look at mechanisms that might be applicable to humans.
  • Why would the microbiota affect the human brain? Because we evolved with a ‘background’ of microbes and have relied on them as we evolved. For example, gut microbes produce metabolites the human body is unable to produce by itself.
  • The newly published paper is titled “The gut virome is associated with stress-induced changes in behaviour and immune responses in mice”.
  • Most microbiota-gut-brain axis research to date has looked at the bacterial component of the microbiome, but this misses the bigger context. The virome is the collection of viruses in the gut, mostly consisting of bacteriophages (which infect bacteria in the gut). This study focused on the virome and how it influenced the gut bacteriome as well as host behavior.
  • Bioinformatics challenges exist when working with the virome for several reasons. For one, distinguishing the biology of a bacteriophage from its host can be challenging.
  • The study used a fecal virome transplant: taking a fecal sample, removing the cellular organisms and small particulates so that the bacteriophages were left over, and then concentrating them and administering them. The researchers took this entire virome from a mouse, then transferred it back to the same individual mouse while it was undergoing stress.
  • After stress, differences were seen in the mouse gut bacteriome and virome. The mice had higher anxiety- and depression-like behaviour, plus changes in their immune systems. But after the fecal virome transplant, some of their behaviours were improved.
  • Do the viruses impact the host nervous system directly, or do they only affect the host by way of the bacteriome? This is not fully known, but there appears to be very little interaction of the bacteriophages with the host. 
  • Analysis of the gut bacteriome or virome must respect the compositional nature of the data. The types of measurements used to analyze the microbiome and virome are confounded by compositional effects, and in the field this is not respected as much as it should be.
  • The next step after this study is to explore the changes in microbiome function in the mice, perhaps pinpointing which bacterial groups need to be changed to normalize the mouse behaviours.

Episode links:

About Nathaniel Ritz:

Dr. Nathaniel Ritz completed his PhD in Prof. John Cryan’s lab at APC Microbiome Ireland where he studied the role of the bacteriome and the virome in social and stress-related disorders. His interests lie in elucidating microbiota-host interactions and establishing microbiota causality within the microbiota-gut-brain axis. Nathaniel has recently moved to Seattle, Washington, USA, to join the lab of Dr. Sid Venkatesh as a postdoctoral fellow at the Institute for Systems Biology to further unravel the mechanisms underpinning microbe-host interaction. Outside of the lab, Nathaniel is an avid rock climber, dog walker, and partner to fellow scientist Dr. Minke Nota. More details and current position can be found at https://venkatesh.isbscience.org/

About Thomaz Bastiaanssen:

Dr. Thomaz Bastiaanssen is the lead bioinformatician in Prof. John F. Cryan’s microbiota-gut-brain axis group in Cork, Ireland. He is interested in the ecological dynamics governing host-microbe communication and how this complex interplay can impact human well-being. He will soon transition to a new role at Amsterdam UMC, the Netherlands, where he will continue to study the microbiome gut-brain axis. Besides working on multi-omics analyses, he enjoys horror stories, tabletop games and spending time with his wife, son, and corgi. His website can be found at: https://thomazbastiaanssen.github.io/

New paper outlines the value of studying probiotics in the small intestine

/in ISAPP Science Blog /by KC

Even though the human digestive tract extends from the mouth down through the small and large intestines, the study of probiotics and their activities has tended to focus on the colon. While the colon (or perhaps more accurately its proxy, the faecal sample) is relatively accessible and easy to study, recently some researchers have argued that crucial information can be gained from looking at another digestive tract site: the small intestine.

A recent paper published in Cell Reports Medicine, titled Small intestine vs. colon ecology and physiology: Why it matters in probiotic administration, laid out the differences between probiotic actions and interactions in the small intestine versus the large intestine. The paper was the result of work by an expert group of the International Life Sciences Institute (ILSI) Europe – the Probiotics Taskforce.

The authors of the paper say the duodenum (the first part of the small intestine) is the most dynamic part of the digestive tract. The small intestine as a whole is the site where most of the body’s digestion and absorption takes place, it is also a site of high immune activity. Even though ingested materials move through this area more rapidly than the large intestine, the small intestine allows closer interaction between host and microbes because it has a lower rate of mucus secretion and looser gut barrier junctions. The microbiota of the small intestine is primarily shaped by the digestion and resulting abundance of simple carbohydrates and amino acids, whereas the colonic microbiota is driven by the metabolism of the remaining complex carbohydrates. These factors and others create very different environments for probiotic interaction and activity.

While the most relevant clinical question for a probiotic strain may be what health benefit it confers in the host, researchers may also be interested in gut microbiota manipulation via probiotics to transform host-microbe interactions at discrete locations in the digestive tract – potentially yielding new or improved benefits for the host. The paper raises the possibility of novel probiotics discovered or developed in the future to specifically target the small intestine.

Accessibility of the small intestine, however, remains a challenge. While animal and in vitro models can lead to valuable insights, the authors of the paper point to the need for more sensitive and cost-effective tools for sampling the small intestine in human study participants.

See this Q&A with the paper’s lead author, Dr. Arthur Ouwehand PhD, Global Health & Nutrition Sciences, International Flavors & Fragrances, Finland.

Why is it important to think about how probiotics interact at sites other than the colon?

Nutrient absorption, entero-hepatic circulation, and energy regulation are all happening in the small intestine and have a major impact on our health. Even some forms of diarrhoea originate from the small intestine. So, we should be better aware what happens in the small intestine and how probiotics may influence these processes.

What clues do we have that the small intestine is an important site for probiotic activity?

The most common argument is that the microbial numbers in the small intestine are much smaller and hence (with less competition) probiotics can better exert an effect there. Is that true? We don’t know yet, because small intestinal samples have been difficult to collect. We need to better understand what is happening in the human small intestine.

Do small intestinal interactions depend on the specific probiotic?

Very likely. Also interesting is how diet would shape the effects of the probiotic in the various parts of the small intestine.

What are some of the main questions researchers still need to address regarding how probiotics act in the small intestine?

  • What is the microbiota in the small intestine and how is it influenced?
  • What do these changes in composition and activity mean?
  • How can the small intestinal microbiota be influenced in a meaningful way?

How do you think researchers will overcome the challenges of gathering information about the small intestine?

Capsules that sample the small intestine are nothing new. They were already developed in the 1960s. Better and more affordable capsules are now coming on the market, so minimally invasive sampling of the human small intestine will soon be much more feasible. These new technologies should expand our understanding of the microbiota in different parts of the small intestine, and how probiotics interact in this environment.

Episode 29: Human milk oligosaccharides in the infant gut

/in Podcast, Season Two /by Laura

Podcast: Play in new window | Download

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The Science, Microbes & Health Podcast 

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

Human milk oligosaccharides in the infant gut, with Dr. Simone Renwick PhD

Episode summary:

In this episode, the ISAPP hosts discuss human milk and the infant gut with Dr. Simone Renwick PhD from Mother-Milk-Infant Center of Research Excellence (MOMI CORE) at UC San Diego, USA. Dr. Renwick talks about her work investigating how communities of microbes versus individual microbes in the infant gut metabolize human milk oligosaccharide (HMO) structures, and what we know about the origin and functions of the microbes contained in human milk.

Key topics from this episode:

  • Dr. Renwick studies how components of human milk foster the development of the infant gut microbiota. These components include HMOs (special sugars found in human milk) and the milk microbiota.
  • HMOs cannot be metabolized by the human body, but when microbes in the infant gut break them down, it has health benefits for the infant (because infants who receive no human milk are predisposed to a range of diseases).
  • Dr. Renwick used in vitro models to mimic infant microbiota communities, and found that these communities rapidly degraded the HMOs. This metabolism increased microbes associated with health and suppressed potentially pathogenic microbes. 
  • Although most research on HMOs focuses on bifidobacteria that are specially equipped to break them down, she looked at individual strains within the infant gut community and found approximately 100 species capable of directly degrading HMOs.
  • Once breastfeeding ceases, some microbes in the infant gut adapt to different sources of sugars, but others greatly decrease in abundance.
  • Microbes act differently in a community than on their own. Within a complex community, microbes that are better equipped to degrade the HMOs will act quickly, producing byproducts that are then are available to other members.
  • All of the different in vitro models have their advantages and disadvantages. The spatial relationships of the human body are often missing in in vitro models.
  • Humans appear to have the highest concentration of milk oligosaccharides of any mammal.
  • The milk microbiota is another active area of investigation. Live microbes are present in the mammary gland, but their source is still unknown. They tend to resemble the composition of the microbiota on the skin as well as the infant oral cavity, but curiously, anaerobic bacteria are also found in the milk microbiota. Somehow these microbes may move from the mother’s gut to the milk. These microbes may not directly metabolize HMOs. (See this paper.)
  • Formula companies are beginning to put HMO structures into their products – mainly 2′-Fucosyllactose.

Episode links:

About Dr. Simone Renwick PhD:

Dr. Simone Renwick is the Milk & Microbes postdoctoral fellow at the Mother-Milk-Infant Center of Research Excellence (MOMI CORE) at the University of California, San Diego, USA. Her research focuses on understanding the role of human milk components, such as the human milk oligosaccharides (HMOs) and milk microbiota, in fostering the developing infant gut microbiota. She is also interested in the potential therapeutic applications of milk components in diseases that affect adults. Currently, Simone is supervised by Drs. Lars Bode, Rob Knight, Pieter Dorrestein, and Jack Gilbert. Prior to her postdoc, Simone completed her PhD in Molecular and Cellular Biology (MCB) at the University of Guelph, Canada, under the supervision of Dr. Emma Allen-Vercoe.

She was the recipient of the Students and Fellows Association poster prize at the ISAPP 2023 meeting in Sitges, Spain.

Episode 26: The role of microbes in gut-brain communication

/in Podcast, Season Two /by Laura

 

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | RSS

The Science, Microbes & Health Podcast 

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

The role of microbes in gut-brain communication, with Prof. Emeran Mayer MD

Episode summary:

In this episode, ISAPP podcast host Prof. Dan Tancredi PhD welcomes guest Prof. Emeran Mayer MD, a gastroenterologist and researcher at University of California Los Angeles. They talk about the microbiota-gut-brain axis, covering its evolutionary origins and how this complex system works in the human body to support overall health.

Key topics from this episode:

  • Microbiota-gut-brain communication has a long evolutionary history: microbes have been around for billions of years and they stored a lot of information in their genes. At some point in evolution microbes got inside the digestive tube of a primitive marine animal called hydra and it proved advantageous for this animal.
  • The hydra shows the origin of the human enteric nervous system (ENS): microbes live inside this tube and transfer genes to the nerve cells of this digestive tube, showing the origin of neurotransmitters.
  • Today in humans the neurotransmitters influence gene expression of microbes and change the microbial behaviors; the metabolites produced feed back to the brain.
  • Prof. Mayer’s initial interest as a gastroenterologist was the ENS and how it regulates motility. Subsequently the ENS was found to regulate many gut functions. The gut also houses a large part of the immune system and a complex hormonal system, and all these systems are connected with each other and communicate with the brain.
  • There is an increasing understanding that many chronic diseases relate to Inappropriate engagement of the immune system, starting in the gut.
  • When Prof. Mayer started in the field, the term “gut health” did not exist. Now it’s a ubiquitous term which has associations with wellbeing, acknowledging the gut has influence on many other body systems.
  • The associations between gut (microbiota) and brain health started with provocative animal experiments from Cork, Ireland, in which researchers manipulated the gut microbiome and found changes in emotion-like behaviors of animals. However, it has been difficult to translate to human interventions.
  • How do microbiome-targeted dietary interventions affect the brain? We do know the “Standard American Diet” (deficient in fiber) has changed the gut microbes in a way that compromises the production and maintenance of the gut barrier. 
  • There are many misconceptions about “leaky gut”, but basically contact between beneficial microbes and immune system sensors stimulate the immune system of the gut to low-grade inflammation. This can alter the tight junctions, making the gut more permeable, and ultimately this can affect the brain. Diet can affect the role of microbes in maintaining an effective gut barrier.
  • Prof. Mayer describes how he ended up studying the microbiota-gut-brain axis – he would not have predicted how important and popular this field would become.
  • In the future, there will be more sophisticated and personalized interventions. He sees a paradigm shift happening from reductionist approaches in medicine to systems biological approaches. This field is making us acknowledge that diet will play a major role.

Episode links:

About Prof. Emeran Mayer MD:

Emeran A Mayer is a Gastroenterologist, Neuroscientist and Distinguished Research Professor in the Department of Medicine at the David Geffen School of Medicine at UCLA, the Executive Director of the G. Oppenheimer Center for Neurobiology of Stress & Resilience and Founding Director of the Goodman Luskin Microbiome Center at UCLA. He is one of the pioneers and leading researchers in the bidirectional communication within the brain gut microbiome system with wide-ranging applications in intestinal and brain disorders. He has published 415 scientific papers, co edited 3 books and has an h-index of 125. He published the best selling books The Mind Gut Connection in 2016, the Gut Immune Connection in June 2021, and the recipe book Interconnected Plates in 2023. He is currently working on a MasterClass and a PBS documentary about the mind gut immune connection. He is the recipient of numerous awards, including the 2016 David McLean award from the American Psychosomatic Society and the 2017 Ismar Boas Medal from the German Society of Gastroenterology and Metabolic Disease.

Biotics in animal and human nutrition

Episode 22: Biotics in animal and human nutrition

/in Podcast, Season Two /by Laura

Biotics in animal and human nutrition

 

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | RSS

The Science, Microbes & Health Podcast 

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

Biotics in animal and human nutrition, with Prof. Kelly Swanson

Episode summary:

In this episode, the ISAPP podcast hosts join guest Prof. Kelly Swanson PhD from University of Illinois at Urbana-Champaign, to discuss the role of biotics in animal and human nutrition. They review the criteria for prebiotics and synbiotics, then discuss how we gain knowledge about nutrition and the role of biotics in animals compared to humans.

Key topics from this episode:

  • A good argument can be made that biotics are essential for our diet; they are beneficial even if efficacy is sometimes difficult to prove.
  • Nutrients have an impact on the host’s health and simultaneously on the host-associated microbes.
  • Health benefits are essential to the FDA definition of fiber.
  • Antibiotics’ effect on the microbiota: short-term effects may be minor, but we still don’t know the long-term effects.
  • The synbiotics definition, criteria for products to meet this definition, and the health outcomes from using these biotic substances.
  • The difference between complementary and synergistic synbiotics.
  • When studying biotics in companion animals (cats and dogs), can results from one host be extrapolated to another host? Final studies should be in the target host.
  • Biotics are important in veterinary medicine and a popular topic of study.
  • Predictions about the future of nutrition science as informed by the microbiome.

Episode links:

Additional resources:

About Prof. Kelly Swanson:

Kelly Swanson is the Kraft Heinz Company Endowed Professor in Human Nutrition at the University of Illinois at Urbana-Champaign. His laboratory studies the effects of nutritional interventions, identifying how diet impacts host physiology and gut microbiota. His lab’s primary emphasis is on gastrointestinal health and obesity in dogs, cats, and humans. Much of his work has focused on dietary fibers and ‘biotics’. Kelly has trained over 40 graduate students and postdocs, published over 235 peer-reviewed manuscripts, and given over 150 invited lectures at scientific conferences. He is an active instructor, teaching 3-4 nutrition courses annually, and has been named to the university’s ‘List of Teachers Ranked as Excellent by Their Students’ 30 times. He serves on advisory boards for many companies in the human and pet food industries and non-profit organizations, including the Institute for the Advancement of Food and Nutrition Sciences and International Scientific Association for Probiotics and Prebiotics.

Episode 17: Using metabolomics to learn about the activities of gut microbes

/in Podcast, Season Two /by Laura

 

Podcast: Play in new window | Download

Subscribe: Apple Podcasts | Spotify | RSS

The Science, Microbes & Health Podcast 

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

Using metabolomics to learn about the activities of gut microbes, with Dr. Anisha Wijeyesekera

Episode summary:

In this episode, the ISAPP podcast hosts address the topic of metabolomics with Dr. Anisha Wijeyesekera, PhD, a Lecturer in the Department of Food and Nutritional Sciences at the University of Reading, United Kingdom. Dr. Wijeyesekera gives an overview of how metabolic profiling works, including the information provided by different biological samples, and discusses how metabolomics can be used to piece together the contributions of microbes to host health.

 

Key topics from this episode:

  • Dr. Wijeyesekera introduces the field of metabolomics and describes it as an essential part of systems biology. Metabolic profiling provides a real-time snapshot of the multiple metabolic processes going on in a system at the time the sample was collected.
  • Metabolites are the end products of metabolism; the gut microbiota is the most metabolically active of the microbiomes in the human body.
  • Methodology depends on what information you hope to uncover from your samples. Different biological samples (e.g. stool, urine, plasma) provide different pieces of information; this is cross-referenced with information on metabolic pathways.
  • One application of metabolomics is in identifying biomarkers that can predict patient outcomes. Identifying differences in microbes as well as metabolites could lead to the development of dietary-based supplements for patients to take alongside clinical treatments.
  • Changes in microbial composition may not be that meaningful if the bugs that change are doing the same thing in the end; this is what metabolomics helps uncover.
  • Metabolomics gives you insights into mechanisms when you have a probiotic or prebiotic trial with clinical outcomes. 
  • Short-chain fatty acids are metabolites that are frequently associated with health; changes in these is a clue that the gut microbiota has been impacted by the intervention.
  • Bile acids are metabolites that come from diet. Microbes convert primary bile acids to secondary, which circulate throughout the body. You can measure bile acids to see how gut microbiota are affected by an intervention.
  • Metabolomics is very promising and may be used in more probiotic and prebiotic studies in the future.

 

Episode abbreviations and links:

 

About Dr. Anisha Wijeyesekera:

Anisha is a Lecturer in the Department of Food and Nutritional Sciences at the University of Reading, United Kingdom. She previously worked at Imperial College London, where she also obtained her PhD (in Biochemistry). Anisha’s research applies a combined microbial and metabolic phenotyping approach, to better understand the tripartite relationship between diet, gut microbiota and human health. At the University of Reading, she conducts in vitro and in vivo studies for functional assessment of the gut microbiota, particularly in response to prebiotics and probiotics. The ultimate aim is to use this information to tailor nutritional or other interventional therapy to improve health outcomes.

Why researchers need to understand more about the small intestinal microbiome

/in ISAPP Science Blog /by KC

By Prof. Eamonn M. M. Quigley, MD, The Methodist Hospital and Weill Cornell School of Medicine, and Prof. Purna Kashyap, MD, Mayo Clinic

The phrase “gut microbiota” properly refers to the microorganisms living throughout the entire digestive tract, including the mouth and the upper digestive tract, through the length of the small intestine as well as the large intestine. Yet the vast majority of scientific studies on the gut microbiota make conclusions based only on stool samples, meaning that the contributions to health and disease of microorganisms from most of the digestive tract are largely unexplored.

Researchers have established that the microorganisms throughout different parts of the digestive tract vary greatly. In particular, the microorganisms living in the small intestine are fewer in number than those in the colon. They are less diverse, and they change more over time because of their dynamic environment (fluctuations in oxygen, digestive secretions, dietary substrates, among other influences).

The dynamic composition and biologic functions of the small intestinal microbiome in health and disease are mostly unknown. Research has been hampered by the difficulty in obtaining samples from this area of the digestive tract and, in particular, its more distal reaches. Participants in a 2022 ISAPP discussion group argued, however, there are some good reasons to dedicate more effort to investigation of the small intestinal microbiome:

  • The small intestine has critical homeostatic functions in relation to nutrient digestion and absorption, immune engagement and interactions with the enteric and central nervous systems, as well as the neuroendocrine system. Each of these could be influenced by microbiota-host interactions. Important locations for these interactions include the gut barrier and mucosa- or gut-associated lymphoid tissue. The nature of microbiota-host interactions in these particular areas needs to be better understood, as they could have implications for systemic host health.
  • Diet plays a critical role in symptom generation in many gastrointestinal disorders; it is important to better understand diet-microbe interactions in the gut lumen to determine how the small intestinal microbiome may be contributing to diet-triggered symptoms.
  • A disordered small intestinal microbiome is commonly implicated in the pathogenesis of various gastrointestinal and non-gastrointestinal symptoms, from irritable bowel syndrome to Alzheimer’s disease, through the much-disputed concept of small intestinal bacterial overgrowth (SIBO). A precise definition of the normal small intestinal microbiome is a prerequisite to the accurate diagnosis of SIBO and linking it with various disease states.

How can we gain more information on the small intestinal microbiome? Our group tackled the limitations of current definitions and diagnostic methods, noting that this field may be advanced in the near future by new technologies for real-time sampling of intestinal gases and contents. The group discussed optimal methods for the sampling of small intestinal microbes and their metabolic products—noting that a full range of ‘omics technologies applied in well-defined populations could lead to further insights. In the meantime, the gastroenterologists in our group advised restraint in the diagnosis of SIBO and the need to exert caution in identifying it as the cause of symptoms. Clinical progress in this area is best achieved through the application of modern molecular methods to the study of human small intestinal microorganisms.

Bifidobacteria in the infant gut use human milk oligosaccharides: how does this lead to health benefits?

/in ISAPP Science Blog /by KC

By Martin Frederik Laursen, Technical University of Denmark, 2022 co-recipient of Glenn Gibson Early Career Research Prize

Breast milk is the ‘gold standard’ of infant nutrition, and recently scientists have zeroed in on human milk oligosaccharides (HMOs) as key components of human milk, which through specific interaction with bifidobacteria, may improve infant health. Clarifying mechanisms by which HMOs act in concert with bifidobacteria in the infant gut may lead to better nutritional products for infants.

Back in early 2016, I was in the middle of my PhD studies working on determinants of the infant gut microbiota composition in the Licht lab at the National Food Institute, Technical University of Denmark. I had been working with fecal samples from a Danish infant cohort study, called SKOT (Danish abbreviation for “Diet and well-being of young children”), investigating how the diet introduced in the complementary feeding period (as recorded by the researchers) influences the gut microbiota development 1,2. Around the same time, Henrik Munch Roager, PostDoc in the lab, was developing a liquid chromatography mass spectrometry (LC-MS)-based method for quantifying the aromatic amino acids (AAA) and their bacterially produced metabolites in fecal samples (the 3 AAAs and 16 derivatives thereof). These bacterially produced AAA metabolites were starting to receive attention because of their role in microbiota-host cross-talk and interaction with various receptors such as the Aryl Hydrocarbon Receptor (AhR) expressed in immune cells and important for controlling immune responses at mucosal surfaces 3,4. However, virtually nothing was known about bacterial metabolism of the AAAs in the gut in an early life context. Further, the fecal samples collected from the SKOT cohort were obtained in a period of life when infants are experiencing rapid dietary changes (e.g. cessation of breastfeeding and introduction of various new foods). Thus, we wondered whether the AAA metabolites would be affected by diet and whether these metabolites might contribute to the development of the infant’s immune system. Our initial results quickly guided us on the track of breastfeeding and bifidobacteria! Here is a summary of the story, published last year in Nature Microbiology5. (See the accompanying News & Views article here.)

We initially looked at the data from a subset of 59 infants, aged 9 months, from the SKOT cohort. Here we found that both the gut microbiome and the AAA metabolome were affected by breastfeeding status (breastfed versus weaned). It is well established that certain bifidobacteria dominate the bacterial gut community in breastfed infants due to their efficient utilization of HMOs – which are abundant components of human breastmilk 6. Our data showed the same, namely enrichment of Bifidobacterium in the breastfed infants, but also indicated that the abundance of specific AAA metabolites were dependent on breastfeeding.

Trying to connect the gut microbiome and AAA metabolome, we found striking correlations between the relative abundance of Bifidobacterium and specifically abundances of three aromatic amino acid catabolites – namely indolelactic acid (ILA), phenyllactic acid (PLA) and 4-hydroxyphenyllactic acid (4-OH-PLA), collectively aromatic lactic acids. These metabolites are formed in two enzymatic reactions (a transamination followed by a hydrogenation) of the aromatic amino acids tryptophan, phenylalanine and tyrosine. However, the genes involved in this pathway were not known for bifidobacteria. Digging deeper we discovered that not all Bifidobacterium species found in the infant’s gut correlated with these metabolites. This was only true for the Bifidobacterium species enriched in the breastfed infants (e.g. B. longum, B. bifidum and B. breve), but not post-weaning/adult type bifidobacteria such as B. adolescentis and B. catenulatum group.

We decided to go back to the lab and investigate these associations by culturing representative strains of the Bifidobacterium species found in the gut of these infants. Indeed, our results confirmed that Bifidobacterium species are able to produce aromatic lactic acids, and importantly that the ability to produce them was much stronger for the HMO-utilizing (e.g. B. longum, B. bifidum and B. breve) compared to the non-HMO utilizing bifidobacteria (e.g. B. adolescentis, B. animalis and B. catenulatum). Next, in a series of experiments we identified the genetic pathway in Bifidobacterium species responsible for production of the aromatic lactic acids and performed enzyme kinetic studies of the key enzyme, an aromatic lactate dehydrogenase (Aldh), catalyzing the last step of the conversion of aromatic amino acids into aromatic lactic acids. Thus, we were able to demonstrate the genetic and enzymatic basis for production of these metabolites in Bifidobacterium species.

To explore the temporal dynamics of Bifidobacteria and aromatic lactic acids and validate our findings in an early infancy context (a critical phase of immune system development), we recruited 25 infants (Copenhagen Infant Gut [CIG] cohort) from which we obtained feces from birth until six months of age. These data were instrumental for demonstrating the tight connection between specific Bifidobacterium species, HMO-utilization and production of aromatic lactic acids in the early infancy gut and further indicated that formula supplementation, pre-term delivery and antibiotics negatively influence the concentrations of these metabolites in early life.

Having established that HMO-utilizing Bifidobacterium species are key producers of aromatic lactic acids in the infant gut, we focused on the potential health implications of this. We were able to show that the capacity of early infancy feces to in vitro activate the AhR, depended on the abundance of aromatic lactic acid producing Bifidobacterium species and the concentrations of ILA (a known AhR agonist) in the fecal samples obtained from the CIG cohort. Further, using isolated human immune cells (ex vivo) we showed that ILA modulates cytokine responses in Th17 polarized cells – namely it increased IL-22 production in a dose and AhR-dependent manner. IL-22 is a cytokine important for protection of mucosal surfaces, e.g. it affects secretion of antimicrobial proteins, permeability and mucus production 7. Further, we tested ILA in LPS/INFγ induced monocytes (ex vivo), and found that ILA was able to decrease the production of the proinflammatory cytokine IL-12p70, in a manner dependent upon both AhR and the Hydroxycarboxylic Acid (HCA3) receptor, a receptor expressed in neutrophils, macrophages and monocytes and involved in mediation of anti-inflammatory processes 8,9. Overall, our data reveal potentially important ways in which bifidobacteria influence the infant’s developing immune system.

Figure 1 – HMO-utilizing Bifidobacterium species produce immuno-regulatory aromatic lactic acids in the infant gut.

Our study provided a novel link between HMO-utilizing Bifidobacterium species, production of aromatic lactic acids and immune-regulation in early life (Figure 1). This may explain previous observations that the relative abundance of bifidobacteria in the infant gut is inversely associated with development of asthma and allergic diseases 10–12 and our results, together with other recent findings13–15 are pointing towards aromatic lactic acids (especially ILA) as potentially important mediators of beneficial immune effects induced by HMO-utilizing Bifidobacterium species.

 

References

  1. Laursen, M. F. et al. Infant Gut Microbiota Development Is Driven by Transition to Family Foods Independent of Maternal Obesity. mSphere 1, e00069-15 (2016).
  2. Laursen, M. F., Bahl, M. I., Michaelsen, K. F. & Licht, T. R. First foods and gut microbes. Front. Microbiol. 8, (2017).
  3. Zelante, T. et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39, 372–385 (2013).
  4. Sridharan, G. V. et al. Prediction and quantification of bioactive microbiota metabolites in the mouse gut. Nat. Commun. 5, 1–13 (2014).
  5. Laursen, M. F. et al. Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut. Nat. Microbiol. 6, 1367–1382 (2021).
  6. Sakanaka, M. et al. Varied pathways of infant gut-associated Bifidobacterium to assimilate human milk oligosaccharides: Prevalence of the gene set and its correlation with bifidobacteria-rich microbiota formation. Nutrients 12, 71 (2020).
  7. Keir, M. E., Yi, T., Lu, T. T. & Ghilardi, N. The role of IL-22 in intestinal health and disease. J. Exp. Med. 217, (2020).
  8. Peters, A. et al. Metabolites of lactic acid bacteria present in fermented foods are highly potent agonists of human hydroxycarboxylic acid receptor 3. PLoS Genet. 15, e1008145 (2019).
  9. Peters, A. et al. Hydroxycarboxylic acid receptor 3 and GPR84 – Two metabolite-sensing G protein-coupled receptors with opposing functions in innate immune cells. Pharmacol. Res. 176, (2022).
  10. Fujimura, K. E. et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat. Med. 22, 1187–1191 (2016).
  11. Stokholm, J. et al. Maturation of the gut microbiome and risk of asthma in childhood. Nat. Commun. 9, 141 (2018).
  12. Seppo, A. E. et al. Infant gut microbiome is enriched with Bifidobacterium longum ssp. infantis in Old Order Mennonites with traditional farming lifestyle. Allergy Eur. J. Allergy Clin. Immunol. 76, 3489–3503 (2021).
  13. Meng, D. et al. Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine. Pediatr. Res. 88, 209–217 (2020).
  14. Ehrlich, A. M. et al. Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells. BMC Microbiol. 20, 357 (2020).
  15. Henrick, B. M. et al. Bifidobacteria-mediated immune system imprinting early in life. Cell 184, 3884-3898.e11 (2021).

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

/in Consumer Blog, ISAPP Science Blog /by KC

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”

/in News, Consumer Blog /by KC

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.

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

/in ISAPP Science Blog, Consumer Blog /by KC

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

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

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

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

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

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

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

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

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

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

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

Prof. Maria Marco, PhD, University of California Davis

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

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

Prof. Bob Hutkins, PhD, University of Nebraska Lincoln

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

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

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

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

Prof. Dan Merenstein, MD, Georgetown University

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

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

Prof. Colin Hill, PhD, University College Cork

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

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

Prof. Dan Tancredi, PhD, University of California Davis

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

See ISAPP’s press release on this paper here.

Precision approaches to microbiota modulation: Using specific fiber structures to direct the gut microbial ecosystem for better health

/in ISAPP Science Blog, News /by KC

By now, hundreds of scientific articles show the differences in gut microbiota composition and function between states of health and disease, leading to the idea that gut microbiota modulation is a promising way to achieve better health. But in practice, changing the complex community of microbes in the gut has proved challenging—the gut microbiota of the average adult is remarkably stable.

When it comes to diet, non-digestible carbohydrates are the main way to provide nutritional support to microbial populations and to modulate these communities, either in composition or in function. Can these dietary fibers be used to modulate the gut microbiota in a precise manner, with the aim of inducing certain health effects?

Prof. Jens Walter of APC Microbiome Ireland addressed this topic in a plenary lecture at the ISAPP 2020 annual meeting, titled: Precision microbiome modulation through discrete chemical carbohydrate structures.

Walter sees the gut microbiota as an complex ecological community of interacting microbes that is remarkably stable in healthy adults (albeit with a high degree of inter-individual variation). In order to precisely modulate gut microbiomes through diet, scientists must consider the ecological principles that shape these communities and determine how they function.

In the lecture, Walter introduced a perspective for using discrete fiber substrates to precisely modulate gut microbiota – a framework first articulated in a 2014 paper by Hamaker and Tuncil. According to this framework, gut microbiomes can be precisely manipulated, whether to achieve a certain microbiota composition or the production of health-relevant metabolites, through the use of specific fiber structures that are aligned with microbes that have the ability to utilize them. Walter explains some of the main challenges of the framework, which relate to the vast inter-individual differences in the gut microbes that are present, and their response to fiber; and discovering the exact dose of a fiber required for reliable changes in a person’s gut microbiota.

At the core of the presentation is a study by the Walter Lab that systematically tested the framework through a human dose-response trial using resistant starches with slight differences in their chemical structure. The findings of the study, which were published this year, illustrate how this ecological concept can be successfully applied. This shows the colonic microbiota can be successfully shaped in a desired manner with discrete dietary fiber structures.

See Prof. Walter’s presentation in full here.

Can the microbiota help protect against viral infections? Summary of an ISAPP discussion group

/in ISAPP Science Blog /by KC

By Drs. Karen Scott, University of Aberdeen, and Sarah Lebeer, University of Antwerp

As part of the ISAPP virtual annual meeting 2020, around 85 members of the ISAPP community joined us in a Zoom discussion forum to discuss the topic: “Do our resident microbes help protect against viral infections?” A scientific perspective on this topic is especially important during the COVID-19 pandemic, when many members of the general public are wondering about actions (if any) they can take to protect themselves before a SARS-CoV-2 vaccine becomes widely available.

We introduced the topic and were joined by several invited experts, who also gave short presentations:

  • Joel Dore (INRAE France)
  • Tine Licht (Technical University of Denmark)
  • Mary O’Connell-Motherway (APC Microbiome, Cork)

The ensuing conversation, open to all participants, was wide-ranging, starting with the gut microbiota and expanding to include the microbiota at other body sites, and the effects of the gut microbiota around the body gut via transport of metabolites. Here are some of the main take-home messages from this discussion.

Components of the microbiota (bacteria, fungi, archaea, viruses and others) at a body site interact with each other. Although scientists often study one component of the (gut) microbiota at a time, members of the microbiota from different kingdoms interact with each other in ways that can be positive or negative for the host. In particular, specific activities of bacteria can be widespread, frequent or rare among members of the microbiota – and it is often the rare activities that have important impacts on the course of a disease: e.g. specific antimicrobial agents produced by some bacteria prevent Salmonella infections in pigs and cure mastitis in cows.

Mechanistic work shows bacteria in the microbiota can prevent, eliminate or promote viral infections. Studies have shown some microbes can prevent attachment of viruses to cell surfaces by offering alternative receptors. In contrast, virus particles can utilise other bacterial cells to “mask” them and facilitate entry into host cells. Other bacteria can stimulate the immune system to promote elimination of a viral infection, while under specific circumstances this same immune activation may promote viral infection. When it comes to the microbiota of the respiratory tract, studies have shown its bacterial members play a crucial defensive role. Probiotics that are already shown to be effective against other viral upper respiratory tract infections may have promise for COVID-19 (either for preventing infection or enhancing recovery), and currently studies are underway to investigate these.

Probiotics or prebiotics could be useful adjuncts to vaccination, but they are not likely to become a reality for COVID-19. Scientists are perennially interested in the topic of vaccine efficacy, and some probiotics have been shown to increase efficacy for widely available vaccines in certain populations. But in the current pandemic, developing a safe and effective vaccine (or vaccines) is the primary concern. Testing the possibility of probiotic or prebiotic combination therapies would be secondary, since the necessary testing would take longer in order to evaluate the adjuvant potential of different probiotic strains. Because the expression of cell surface molecules that can mediate adjuvant activity is strain-dependent, screening and selecting the best strains would probably take too long to become a reality for COVID-19. Certainly, participants agreed that introduction of a safe, effective vaccine was the priority, without any delays to test out ‘extras’.

A scientific rationale exists for maintaining gut microbiota diversity in order to reduce the development of diseases which, as “underlying health conditions”, may result in more severe COVID-19 outcomes. It is clear that individuals with certain underlying health conditions—related to the central nervous system and gastrointestinal system, and to metabolic and immunological dysfunction—tend to experience a more severe disease, with worse outcomes, following SARS-CoV-2 infection. Many of these conditions are also associated with a gut microbiota that is different from that of healthy controls. Research consistently shows that individuals with metabolic disease, for example, have a less diverse, lower ‘richness’ microbiota, which is often linked to increased intestinal permeability, higher gut inflammation and more oxidative stress throughout the body. This increased oxidative stress then exacerbates the microbial dysbiosis, causing more inflammation and increased intestinal permeability – creating a vicious cycle effect. This cycle is linked with obesity and metabolic disorders. In healthy individuals who are at risk of developing such conditions, the diversity of the existing resident microbiota may be increased by the application of prebiotics or synbiotics, included within a healthy, diverse, high-fibre diet. These approaches may improve bacterial fermentation in the large intestine, resulting in increased production of important bacterial metabolites that help regulate host metabolism, including short-chain fatty acids.

Until a SARS-CoV-2 vaccine is available, supporting a diverse and complex gut microbiota through diet may contribute to maintaining health in at-risk populations. Despite the intense worldwide scientific efforts and collaborations, it is unlikely that an effective vaccine against COVID-19 will be widely available soon. In the meantime, we have to protect ourselves and our local ‘at-risk’ populations as best we can. We are learning more and more about the mechanisms of dietary fibre’s health effects, in which gut bacteria play a major role. Evidence suggests that keeping our gut microbiota as complex and diverse as possible by consuming a high-fibre diet (supplemented by fermented foods, probiotics and prebiotics) might help mitigate susceptibility to infections in general.

Prebiotics do better than low FODMAPs diet

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

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

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

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

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

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

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

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

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

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

 

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

 

Additional reading:

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

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

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

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

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

 

 

ISAPP’s 2019 annual meeting in Antwerp, Belgium: Directions in probiotic & prebiotic innovation

/in featured, News /by ISAPP

Kristina Campbell, Microbiome science writer, Victoria, British Columbia

We live in a time when a simple Google search for ‘probiotics’ produces over 56.8 million hits; a time when almost everyone has heard of probiotics through one channel or another, and when an ever-increasing variety of probiotic and prebiotic products is available in different regions of the world.

The next five to ten years will be telling: will probiotics and prebiotics join the ranks of other trendy health products that experienced a wave of popularity before something else took their place? Or will they be recognized as important contributors to health through the lifespan, and establish a permanent position in the clinical armamentarium?

According to the global group of 175 academic and industry scientists who met for the ISAPP annual meeting in Antwerp (Belgium) May 14-16, 2019, one thing above all is necessary for the world to recognize the significance of probiotics and prebiotics for health: scientific innovation. Not only are technological capabilities advancing quickly, but also, new products are being evaluated by better-educated consumers who demand more transparency about the health benefits of their probiotics and prebiotics.

Participants in the ISAPP conference came together to talk about some of the leading innovations in the world of probiotics and prebiotics. Here are three of the broad themes that emerged:

Better health through the gut-brain axis

Gut-brain axis research is rapidly growing, with many investigators in search of probiotic and prebiotic substances capable of modulating brain function in meaningful ways. Phil Burnett of Oxford (UK) presented on “Prebiotics, brain function and stress: To what extent will prebiotics replace or complement drug therapy for mental health?”. Burnett approached the challenge by administering prebiotics to healthy adults and giving them a battery of psychological tests; in one experiment he found people who consumed a prebiotic (versus placebo) showed benefits that included reduced salivary cortisol and positively altered emotional bias. For those with diagnosed brain disorders, Burnett concludes from the available data that prebiotics have potential anxiolytic and pro-cognitive effects in these populations, and that prebiotics may eventually be used to complement the established treatments for some mental disorders.

Short-chain fatty acids (SCFAs) are of interest as potential modulators of brain function, but so far very little research has been carried out in this area. Kristin Verbeke of Leuven (Belgium) gave a talk entitled “Short-chain fatty acids as mediators of human health”, which covered the extent to which interventions with fermentable carbohydrates can alter systemic SCFA concentrations (rather than gut SCFA concentrations)—since the former are more relevant to effects on the brain.

Also, a students and fellows feature talk by Caitlin Cowan of Cork (Ireland) explored a role for the microbiota in psychological effects of early stress. She spoke on the topic “A probiotic formulation reverses the effects of maternal separation on neural circuits underpinning fear expression and extinction in infant rats”.

A clear definition of synbiotics

Immediately before the main ISAPP meeting, a group of experts met to propose a consensus definition of ‘synbiotic’, with the objective of clarifying for stakeholders a scientifically valid approach for the use of the increasingly-popular term. A key point of discussion was whether the probiotic and prebiotic substances that make up a synbiotic are complementary or synergistic. And if the two substances have already been tested separately, must they be tested in combination to give evidence of their health effect? The group’s conclusions, which will undoubtedly steer the direction of future R&D programs, will be published in a forthcoming article in Nature Reviews Gastroenterology & Hepatology.

Probiotics and prebiotics for pediatric populations

Probiotics and prebiotics have been studied for their health benefits in pediatric populations for many years, but in this area scientists appear to have a renewed interest in exploring new solutions. Maria Carmen Collado of Valencia (Spain) covered “Probiotic use at conception and during gestation”, explaining some of the most promising directions for improving infant health through maternal consumption of probiotics.

In recent years, technical advancements have made possible the large-scale production of some human milk oligosaccharides (HMOs); it is now an option to administer them to infants. Evelyn Jantscher-Krenn of Graz (Austria) presented a novel perspective on HMOs, with “HMOs in pregnancy: Roles for maternal and infant health”, giving a broad overview of the many ways in which HMOs might signal health status and how they might be fine-tuned throughout a woman’s pregnancy.

A discussion group on “prebiotic applications in children”, chaired by Dr. Michael Cabana of San Francisco (USA) and Gigi Veereman of Brussels (Belgium), discussed evidence-based uses of prebiotics in children in three areas: (1) prevention of chronic disease; (2) treatment of disease; and (3) growth and development. While the latter category has the best support at present (specifically for bone development, calcium absorption, and stool softening), the other two areas may be ripe for more research and innovation. The chairs are preparing a review that covers the outcomes of this discussion group.

Next year in Banff

ISAPP’s next annual meeting is open to scientists from its member companies and will be held on June 2-4, 2020 in Banff, Canada.

 

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

New ISAPP video gives an overview of fermented foods and their health benefits

/in featured, News /by Mary Ellen Sanders

Fermented foods are not the same as probiotic-containing foods. So what’s the difference? Do both of them confer the same health benefits?

These topics are addressed in ISAPP’s latest video, which takes viewers through the scientific basics of fermented foods (see here). Yogurt, kimchi, and cheese fall into this category of foods, which are transformed by growth and metabolic activity of microbes.

Some fermented foods contain live microbes that travel through the digestive tract, interact with cells, and support the intestinal microbiota. Their potential health benefits are of interest, too: not only do fermented foods improve digestibility, but initial studies show they also improve the immune system and prevent acute illnesses.

The upshot? Naturally fermented foods are worth incorporating in your daily diet.

This educational video was commissioned by the ISAPP board of directors with input from several additional scientific experts.

ISAPP’s prebiotics & probiotics infographic now available in Russian

/in featured, News /by Mary Ellen Sanders

‘International’ is the first word in ISAPP’s title—and the organization takes seriously its commitment to advancing education about probiotics and prebiotics in countries around the world. ISAPP members are happy to announce that the infographic “Effects of Prebiotics and Probiotics on our Microbiota” is now available in Russian. See here.

In an effort to reach broader global populations with its science-based communications on probiotics, prebiotics and fermented foods, ISAPP is undertaking steps to translate its infographics into multiple languages. Expected in the next month are translations of ISAPP’s popular “Probiotics” and “Prebiotics” infographics, which will be available in Bulgarian, Chinese, Dutch, French, Indonesian, Italian, Polish, Portuguese, Russian, and Spanish. (See here for all available translations of ISAPP infographics.)

The translation efforts, led by Dr. Roberta Grimaldi from University of Reading (UK), are made possible by many translators who are contributing generously of their time and skills.

Importance of understanding probiotic mechanisms of action

/in featured, ISAPP Science Blog /by Mary Ellen Sanders

By Prof. Sarah Lebeer, Universiteit Antwerpen, Belgium

At present, we do not fully understand the mechanistic basis of many well established probiotic health benefits. This limits our ability to predict which probiotics are likely to be effective.

For instance, prevention of antibiotic-associated diarrhea and necrotizing enterocolitis are health benefits that are well substantiated by meta-analyses, which combine results on many probiotic strains. But what the effective strains have in common from a mechanistic perspective is not known. We cannot yet pinpoint one or a few molecules produced by these strains that might drive the clinical effects. This is likely due to interplay between both host and probiotic factors. These health conditions are complex pathologies and the probiotic strains are living micro-organisms likely working through multiple mechanisms and molecules.

This is in contrast to some more clearly defined situations. Lactose maldigestion results from a deficiency in the enzyme lactase, which is required for converting lactose to glucose and galactose in the small intestine. If lactose is not broken down, it reaches the colon and is fermented by the gut microbiota, leading to symptoms. Some probiotic bacteria (including those present in yoghurt) contain lactase, which can reduce the typical symptoms of lactose digestion.

Several colleagues and I published a recent paper (Kleerebezem et al. 2019) discussing the importance of understanding mechanisms of action. We argue that such knowledge will enable: “(i) selection of more effective probiotic strains; (ii) optimization of probiotic product manufacturing and quality assurance, (iii) improved design of probiotic formulation, and (iv) support of the design of effective clinical trials with the best chance of realizing benefits to human health.”

While knowledge of the mechanism of action is not necessary for translation to effective products, it provides important insights that can improve actions throughout the translational pipeline.

The strain-specificity of different mechanisms of action is another point that will be clarified by future mechanism-focused research. Different probiotic strains clearly express different mechanisms, but some mechanisms are also shared (Sanders et al. 2018). How different host- and probiotic-specific factors interact to achieve a clinically successful intervention remains to be unraveled.

ISAPP’s 2019 Annual Meeting Program Released

/in featured, News /by Mary Ellen Sanders

ISAPP is pleased to announce the release of the official program for its 2019 Annual Meeting, scheduled for May 14-16, 2019, in Antwerp. Unlike the 2018 ISAPP meeting in Singapore, which was an open registration meeting, the 2019 event will comprise only invited academic experts and industry scientists from member companies. For program details, see the meeting website.

The 2019 program offers a strong lineup of probiotic, prebiotic and microbiome presentations. Featured topics include human milk oligosaccharides, learnings from the Flemish Gut Flora project, and leveraging political infrastructure to advance important science and public health messaging. Half-day breakout discussion groups are scheduled for May 15th, covering timely topics relevant to both industry and clinical practice, such as recommended dietary allowance (RDA) for live cultures, and the use of probiotics and prebiotics as adjuncts to drugs. Prof. Glenn Gibson will host the “fishbowl”, a session designed to integrate audience and experts’ perspectives in an interactive format; this year’s topic is: What can scientists and industry do to spring probiotics and prebiotics into mainstream health management?

For companies interested in participating in this meeting, now’s the time to join ISAPP and become part of its active industry advisory committee. Details on industry membership can be found here. ISAPP’s industry members help ISAPP achieve its mission of advancing the science of probiotics and prebiotics—see  here for a summary of our latest accomplishments.

Students and fellows will constitute an important presence at the annual meeting. Members of the ISAPP students and fellows association (SFA) will be keen participants, having organized a poster session as well as two SFA oral presentations. The group will also run a half-day parallel student-focused program.

The local host for ISAPP’s 2019 Annual Meeting, Prof. Sarah Lebeer, University of Antwerp, is excited to welcome her ISAPP colleagues to Antwerp. The history of Antwerp goes back to the 4th century and today the city remains an important European cultural and trade center. ISAPP Annual Meeting participants are invited to join a riverboat trip and dinner to get to know this historic city.

 

 

ISAPP Releases a Mission-Based Summary of 2018 Activities

/in featured, News /by Mary Ellen Sanders

The mission of ISAPP is to advance scientific excellence in probiotics and prebiotics. ISAPP is an independent, science-based voice for the probiotic and prebiotic fields. The newly released short summary details ISAPP’s accomplishments in 2018 based around the core value of Stewardship, Advancing the Science, and Education. See here for the summary, also featuring ISAPP’s recent publications.

Thank you to the ISAPP Board of Directors for their leadership, dedication and scientific expertise, making these accomplishments possible.

Thank you to the Industry Advisory Committee for their ongoing support of ISAPP, providing the resources needed for ISAPP to accomplish its mission to advance the science of probiotics and prebiotics.

Click here to see the 2018 Summary.

See all Annual Reports and Short Summaries here.

YOGURITO –the Argentinian social program with a special yogurt

/in featured, ISAPP Science Blog /by Mary Ellen Sanders

Dra. María Pía Taranto, CERELA-CONICET, Argentina and Prof. Seppo Salminen PhD, University of Turku, Finland

It is widely accepted that technologies play a central role in the processes of social change. The Argentinian experience has documented that yogurt can be a promising tool for promoting social development.  The program is called “Scholar Yogurito, the social probiotic” and the probiotic product is called “Yogurito”. This social program began with the development of a probiotic food, in the form of yogurt. This yogurt contains the probiotic strain Lactobacillus rhamnosus CRL1505, whose functional and technological characteristics are widely documented by CERELA-CONICET researchers. These researchers conducted clinical studies that demonstrated that the consumption of this probiotic product improves natural defenses and prevents respiratory and intestinal infections, the infectious events of greatest relevance in childhood. The “Yogurito Social Program” benefits some 300,000 schoolchildren in the province of Tucumán and some 50,000 in other provinces and municipalities of Argentina. This social transfer project, implemented in 2008 in the province of Tucumán, is a paradigm of interaction between the scientific sector, the manufacturing sector and the state, to improve the quality of life of highly vulnerable populations.

The social and economic implications for such translational research are significant and especially pertinent for people living in poverty, with malnutrition and exposure to environmental toxins and infectious diseases including HIV and malaria. This example of probiotic applications illustrates the power of microbes to positively impact the lives of women, men, and children, right across the food value chain. The researchers are looking for grants that would enable them to compare outcomes of schools given Yogurito to schools with no participation in the program.

 

Additional 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.

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. Benef Microbes. 2018 Sep 18;9(5):707-715. doi: 10.3920/BM2018.0015.

 Senior Researcher Maria Pia Taranto and the Yogurito product

 

Maria Luz  Ovejero, a teacher at Primary School 252 Manuel Arroyo y Pinedo, explains probiotics to 4-6 year old children in Tucuman province in Argentina