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Episode 38: Microbes that break down mucus and milk to benefit the host, with Dr. Clara Belzer PhD

We discuss microbes, mucus, and milk with Dr. Clara Belzer PhD from Wageningen University in the Netherlands in this episode. Dr. Belzer, a molecular geneticist, specializes in studying the microorganisms that are equipped to break down the glycans in mucus and human milk within the host environment.

Key topics from this episode:

  • Dr. Belzer’s research focuses on the microbes living in the host that survive on glycans (chains of sugars) produced by the host: milk oligosaccharides and mucus. The host is not good at digesting these sugars, but can use them when they’re separated into smaller components. These long chains of sugars end up in the large intestine, where certain microbes begin to digest them.
  • There seems to be an evolutionary adaptation that sustains the symbiotic relationship between human milk and bacteria in the infant gut; many immune molecules in the human milk suppress pathogens, so the human milk oligosaccharides (HMOs) are available to the bacteria in the infant gut that can break them down. The bacteria are not suppressed by the acidic environment in the infant gut.
  • Human milk is the best food for infants, but innovations in infant formula may make it more similar to human milk.
  • Akkermansia is a genus of bacteria mostly found in adults, but also sometimes in infants, which grows in the mucosal layer of the intestines. (It doesn’t survive on dietary glycans.) Dr. Belzer’s hypothesis is that the environment created by human milk in the infant gut also fosters bacteria that can grow on mucus, creating a succession of host-benefitting bacteria. They found that HMOs, in addition to mucus, can support the growth and survival of Akkermansia, potentially helping it build a microbial network.
  • There’s a genetic component to the HMOs contained in human milk; similarly, the sugar content in the mucosal glycans is related to host genetics.
  • Lean individuals have a higher abundance of Akkermansia; these bacteria improve metabolism (for example, increasing insulin sensitivity) and have effects on the immune system, which both contribute to a lean phenotype. The root of these effects may be the strengthening of the gut barrier, which dampens signals from the lumen.
  • Dr. Belzer has used both omics and culture-based approaches in her research. As part of her research she tries to make microbial synthetic communities, growing them in the lab and stimulating them with different glycans. This technique yields insights about the functions and microbial ecology in the gut.
  • Killed Akkermansia are still able to bring health benefits to the host. Dr. Belzer had the idea that the pili structures on the bacteria were what communicated with the host, and sure enough, this was borne out in a study that showed the proteins in the pili (Amuc_1100) remained intact in the pasteurized bacteria and could stimulate the host immune system. This is a valuable finding because Akkermansia are difficult to culture.
  • When Akkermansia fails to occupy the niche in the mucus layer, Bacteroides species may occupy the niche instead, forming a different microbial community in the mucus. Research is ongoing about the effects of different microbes carrying out similar functions for the host. Furthermore, scientists have many more microbial functions to discover.

Episode abbreviations and links:

About Dr. Clara Belzer PhD:

Dr. Clara Belzer is Associate Professor Microbiology at the Laboratory of Microbiology of Wageningen University. The Belzer group is called ‘Microbes Mucus and Milk’ and the research is focused on the interaction of the gut microbiome with host mucus and milk. After obtaining her PhD at the Erasmus Medical Center Dr. Belzer did a postdoc at Harvard medical school. By now Dr. Belzer has years of experience on gut microbiome studies on anaerobes, including synthetic communities and different biotic concepts, with a special interest for the Akkermansia muciniphila. The group of Dr. Belzer works on several microbiome HMO and mucus related topics funded by national and international grants, some also in collaboration with medical centers and industry.

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

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/

Episode 32: How microbes and mucus interact in the gut

How microbes and mucus interact in the gut, With Dr. Mindy Engevik PhD

How microbes and mucus interact in the gut, With Dr. Mindy Engevik PhD

Episode summary:

In this episode, the ISAPP hosts discuss mucus-microbe interactions in the digestive tract with Dr. Mindy Engevik PhD from the Medical University of South Carolina, USA. They discuss how mucus in the gut is produced and degraded, and different ways that pathogens and commensal microbes interact with the mucus layer. Dr. Engevik describes some different ways that commensal bacteria make use of mucus, as well as dietary influences on gut mucus production.

Key topics from this episode:

  • The gut epithelium has special cells called goblet cells that actively secrete mucus. In the small intestine, mucus forms a light barrier but in the colon, it forms a thicker barrier with two layers: an inner layer free of microbes, and an outer layer where mucus and microbes coexist.
  • Bacteria in the gut make use of mucus in different ways. Many microbes have the capacity to degrade mucus, and it can provide a carbon source for bacteria to survive. Even bacterial quorum sensing can be influenced by mucus.
  • Bifidobacteria increase mucus production. Akkermansia are good at degrading mucus and also increasing mucus production. Pathogens, however, degrade the mucus and cause inflammation so mucus production is suppressed.
  • Several human diseases involve a dysfunctional gut mucus layer – for example, inflammatory bowel disease.
  • Various models are used for studying mucus – for example, traditional cell lines and human intestinal organoids.
  • Dr. Engevik’s work has found interactions between Clostridioides difficile and Fusobacterium nucleatum in the gut: these bacteria can interact to form biofilms that are more antibiotic-resistant than normal.
  • Individual differences exist in gut microbes as well as glycan structure in the gut, so the best insights will likely come from understanding the entire network of microorganisms, metabolites, and mucus. 
  • Dietary components influence the gut microbiota, which influences mucus production in the gut. High dietary fiber increases the amount of mucus produced by the goblet cells. Some bacteria degrade dietary substrates, then switch over to mucus when they don’t get what they need from the diet.
  • Dr. Engvik is an avid science communicator and advocates for scientists being present on social media. She has found science communication a great way to engage with the public as well as fostering scientific collaborations. The Instagram account showing microscopy images from her lab is @the_engevik_labs

Episode links:

About Dr. Mindy Engevik PhD:

Mindy Engevik is an Assistant Professor at the Medical University of South Carolina. She has Ph.D. in Systems Biology & Physiology and an interest in microbe-epithelial interactions in the gastrointestinal tract. Her lab focuses on how commensal friendly bacteria in the human gut interact with intestinal mucus and she tries to leverage this information to treat intestinal disorders. You can follow her on Twitter at @micromindy.

Episode 31: Microbial species and strains: What’s in a name?

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.

Microbial species and strains: What’s in a name? with Dr. Jordan Bisanz PhD

Episode summary:

In this episode, the ISAPP podcast hosts speak with Dr. Jordan Bisanz PhD, Assistant Professor of Biochemistry and Molecular Biology at Penn State University in State College, USA. They discuss how to define a bacterial strain, the diversity of strains within a species, and how genetic differences correspond with functional differences. They also talk about manipulating microbial communities for insights about health and disease.

Key topics from this episode:

  • Dr. Bisanz says just because strains within a species are genetically related doesn’t mean they do the same things. Bacteria gain and lose genes rapidly, but we don’t yet know what a lot of those genes do.
  • Natural variation in strains can be used as a tool to find out the functions of genes. 
  • Metagenomics illuminates strain-level differences, but that assumes we know what makes a strain. There’s no single accepted definition of a strain.
  • Knowing the mechanisms behind the effects of a strain on a host is important for predicting if closely related strains will have the same effect.
  • Moving forward, it could be useful to have functional information to go along with strains and their taxonomic descriptors.
  • Dr. Bisanz’s lab tests experimentally how microbial genes are gained and lost in vivo, both through wetlab experiments and computational approaches.
  • Experiments on strains are essential – for example, two strains with differences in 1000 SNPs might be functionally the same, while differences in 2-3 key SNPs might make a big difference.
  • When testing probiotic effects, you may be testing something derived from the original microbial genome but not identical. How can this be managed in industry? Understanding the mechanisms is important, strains that function similarly can qualify as the same strain.
  • A microbiome involves multiple microbes working together, acting differently from all the strains in isolation.
  • Dr. Bisanz studies tractable microbial communities: find the microorganisms that are different in a disease state compared to a healthy state, and create a synthetic community of the microbes that are absent. What are the functions of this community?
  • The challenge is that microbiologists need to be able to manipulate the microbes but cannot do this in a whole human fecal sample.
  • Is gut microbiome sequencing useful? At the level of individual, it may not provide value. But putting the data all together, in the future it may provide interesting information. The challenge with interpretation is that the microbiome is driving, but also responding to, dietary inputs.
  • In the microbiome field, gnotobiotic models (using humanized mice) need to be taken a step further than they currently go – specifying not only which microbes established in the host, but also how they could plausibly affect the mechanism.

Episode abbreviations and links:

Additional resources:

About Dr. Jordan Bisanz PhD:

Jordan Bisanz is an assistant professor of Biochemistry and Molecular Biology at the Pennsylvania State University and the One Health Microbiome Center. The Bisanz lab combines computational analyses and wet lab experimentation to understand how gut microbes interact with each other and their host. The lab specializes in coupling human intervention studies with multi ‘omics approaches and gnotobiotic models to understand how host-microbe interactions shape health generating both mechanistic insights and translational targets.

Episode 29: Human milk oligosaccharides in the infant gut

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

 

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.

Episode 25: The effects of metabolites in the colon

 

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 effects of metabolites in the colon, with Prof. Kristin Verbeke PhD

Episode summary:

In this episode, the ISAPP podcast hosts talk about colonic metabolites with Prof. Kristin Verbeke PhD, from KU Leuven, Belgium. She talks about characterizing microbial metabolism in the colon and the consequences of producing various metabolites, both beneficial ones (such as short-chain fatty acids) and potentially detrimental ones.

Key topics from this episode:

  • Prof. Verbeke is a pharmacist by training, and now leads hospital breath testing and carries out research on microbial metabolites in the gastrointestinal tract, including how prebiotics and probiotics can change bacterial metabolism.
  • The majority of protein in the diet is digested in the small intestine, but about 5% of animal protein and 10-15% of plant protein reaches the large intestine to be fermented by the microbiota. This produces metabolites, which are shown in vitro to be toxic. However, in vivo there is less evidence of toxicity; the negative effects of these metabolites may be reduced by the interactions of different compounds in the colon.
  • Short-chain fatty acids (SCFAs) are produced when the body digests dietary fiber, and Prof. Verbeke’s group and others are investigating whether they are responsible for the benefits of eating fiber.
  • Most SCFAs are quickly absorbed in the large intestine, and they serve as an energy source for the cells. They then travel to the liver via portal circulation, where they have additional functions. What’s left over reaches systemic circulation.
  • The difficulty is knowing how many SCFAs are produced in the colon, and how many reach systemic circulation. In one experiment, they labeled the SCFAs that were administered to the colon via capsule; 36% ended up in systemic circulation. Further, when SCFAs were administered at physiological doses the subjects receiving them (compared to placebo) showed a lower cortisol response to stress.
  • SCFAs also affect fat oxidation and fat synthesis in the liver. Their relevance to non-alcoholic fatty liver disease are being investigated.
  • It’s important to eat fiber, and lots of different types. After fiber consumption, SCFAs increase in a sustained manner and take about 8h to get back to baseline. But with SCFA delivery via capsule they spike quickly and then disappear.
  • As for coatings to deliver to the colon, some coatings are time-dependent, pH dependent, etc. and this is an area for further exploration.

Episode links:

About Prof. Kristin Verbeke PhD:

Kristin Verbeke graduated from the KU Leuven, Belgium as a pharmacist in 1991. She obtained a PhD in Pharmaceutical Sciences at the Laboratory of Radiopharmaceutical Chemistry in 1995 and subsequently spend a postdoctoral period in developing radioactively labelled compounds. In 2002, she was appointed at the department of gastroenterology of the Medical Faculty of the Leuven University where she got involved in the use of stable isotope labelled compounds to evaluate gastrointestinal functions. Within the University Hospitals Leuven, she is responsible for the clinical application of diagnostic 13C- and H2-breath tests. Her current research interest specifically addresses the microbial bacterial metabolism in the human colon. Her team has developed several analytical techniques based on mass spectrometry and stable isotope or radioisotope technologies to evaluate several aspects of intestinal metabolism and function in humans (transit time, intestinal permeability, carbohydrate fermentation, protein fermentation, metabolome analysis). Collaborative research has allowed showing an aberrant bacterial metabolism in patient groups with end stage renal failure, inflammatory bowel diseases, irritable bowel disorders and alcohol abuse. These collaborations all have resulted in high quality peer-reviewed papers. In addition, she showed the impact of dietary interventions (modulation of macronutrient composition, pre- or probiotic interventions) on the microbial metabolism and its impact on health. As a PI, she acquired grant support from the university and different funding bodies and successfully completed these projects. Similarly, she supervised several PhD projects that all resulted in the achievement of a PhD degree. Her research resulted in over 200 full research papers. Together with colleague Prof. J. Delcour, she was the beneficiary of the W.K. Kellogg Chair in Cereal Sciences and Nutrition (2010-2020). She is the president of the Belgian Nutrition Society, the vice-chair of the Leuven Food Science and Nutrition Center, and the co-chair of the Prebiotic task force at ILSI Europe. Furthermore, Kristin Verbeke is the editor of the journal Gut Microbiome and member of the editorial board of Gastrointestinal Disorders. Kristin joined the ISAPP Board of Directors in 2023.

Episode 24: Reflections on the probiotic field and ISAPP’s role

 

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.

Reflections on the probiotic field and ISAPP’s role, with Dr. Mary Ellen Sanders PhD

Episode summary:

In this episode, the ISAPP podcast hosts talk about how the probiotic field has evolved over the past 20 years with Dr. Mary Ellen Sanders PhD, ISAPP’s outgoing executive director. She describes how ISAPP is a unique organization advancing the science in the field, highlights what she has enjoyed about being a part of the ISAPP community, and looks ahead to the future of the field.

Key topics from this episode:

  • Sanders describes her career path and how it led to her role with ISAPP. 
  • Both ISAPP and Sanders’ role have changed over time, but she always appreciated two things: great scientific discussions, and interacting with an excellent board of directors.
  • ISAPP has always been dedicated to following the science, highlighting where the evidence is but also the shortcomings of the evidence.
  • The development of microbiome science changed the field of probiotics but it remains important to focus on what probiotics can do for health, rather than what they can do for the microbiome.
  • Mechanisms are important to elucidate, but the most important thing is whether a product impacts health.
  • Sanders says regulations are needed and in the future she hopes regulators will reach out to the expert scientists more frequently and be clear about the standards they expect for a claim.
  • ISAPP meetings are unique–both scientifically enlightening and a lot of fun. Longtime ISAPP board member Gregor Reid had the initial idea for the successful ‘discussion groups’ held every year. 
  • In the future, Sanders thinks probiotics will be used more precisely, like medicines. But also the concept of live dietary microbes may become more popular, with quantities of safe microorganisms being consumed for health benefits.

Episode links:

About Dr. Mary Ellen Sanders PhD:

Mary Ellen Sanders, PhD has served in several roles within ISAPP. She was the founding president, executive science officer and executive director and has retired from ISAPP as of June 30, 2023. She is also a consultant in the area of probiotic microbiology. She works internationally with food and supplement companies to develop new probiotic products and offers perspective on paths to scientific substantiation of probiotic product label claims. She is the current chair of the United States Pharmacopeia’s Probiotics Expert Panel, was a member of the working group convened by the FAO/WHO that developed guidelines for probiotics and serves on the World Gastroenterology Organisation Guidelines Committee preparing practice guidelines for the use of probiotics and prebiotics for gastroenterologists.

Episode 23: Studying microbial ecosystems and how they support health

 

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.

Studying microbial ecosystems and how they support health, with Prof. Emma Allen-Vercoe PhD

Episode summary:

In this episode, the ISAPP podcast hosts talk about microbial ecosystems with Prof. Emma Allen-Vercoe PhD from the University of Guelph in Canada. Prof. Allen-Vercoe describes how her lab brings together information from microbial sequencing and culturing to learn about the human gut microbiome and how it supports health. She discusses what we know about the industrialized gut microbiome and possible ways to improve health by manipulating it.

Key topics from this episode:

  • What the microbiome is and the suite of tools that are typically used to study it.
  • Allen-Vercoe does both sequencing and culturing in her lab as well as metabolomics, proteomics, and transcriptomics to discover on a molecular level at what the microbes are doing. They have a model system called “Robogut” to study microbial ecosystems.
  • Culturing is still crucial and it’s important for trainees in microbiology to gain experience culturing organisms that are less straightforward to grow. The late Sydney Finegold inspired others to try culturing more challenging microorganisms.
  • The challenge of culturing is matching the techniques in the lab to what happens in nature when it grows. Her lab builds metagenome-associated genomes to be able to predict the particular substrates that a certain microbe needs to grow.
  • The “missing microbes” hypothesis is that the human microbiome has been depleted over a few generations in people from industrialized societies, and this correlates with an increase in chronic diseases.
  • The Yanomami people from South America have very diverse gut microbiomes and they share certain species with other non-industrialized societies very distant from them around the world, which are not found in industrialized populations. People in industrialized societies are never exposed to these microbes, but even if they were, the microbes might not stick around because the substrates needed to sustain them  (e.g. through the diet) are absent. 
  • The industrialized microbiome is not necessarily ‘bad’ but we do have to find out more about whether the lack of certain microbes has health effects. This is possible through the Robogut system, which can perturb microbial ecosystems and look at their behavior without affecting people’s health.
  • Fecal transplants have limitations, so they’ve started to work on therapeutic ecosystems. These are “clean” or defined ecosystems that can be administered therapeutically.

Episode links:

About Prof. Emma Allen-Vercoe PhD:

Emma obtained her BSc (Hons) in Biochemistry from the University of London, and her PhD in Molecular Microbiology through an industrial partnership with Public Health England. Emma started her faculty career at the University of Calgary in 2005, with a Fellow-to-Faculty transition award through CAG/AstraZeneca and CIHR, to study the normal microbes of the human gut. In particular, she was among the few that focused on trying to culture these ‘unculturable’ microbes in order to better understand their biology. To do this, she developed a model gut system to emulate the conditions of the human gut and allow communities of microbes to grow together, as they do naturally. Emma moved her lab to the University of Guelph in late 2007, and has been a recipient of several Canadian Foundation for Innovation Awards that has allowed her to develop her specialist anaerobic fermentation laboratory further. This has been recently boosted by the award of a Tier 1 Canada Research Chair in Human Gut Microbiome Function and Host Interactions. In 2013, Emma co-founded NuBiyota, a research spin-off company that aims to create therapeutic ecosystems as biologic drugs, on a commercial scale. The research enterprise for this company is also based in Guelph.

How to navigate probiotic evidence and guidelines for pediatric populations

Episode 20: How to navigate probiotic evidence and guidelines for pediatric populations

How to navigate probiotic evidence and guidelines for pediatric populations

 

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.

How to navigate probiotic evidence and guidelines for pediatric populations, with Dr. Hania Szajewska

Episode summary:

In this episode, the ISAPP podcast hosts talk about evidence and guidelines for probiotics in pediatric populations, with Prof. Hania Szajewska MD PhD, of the Department of Paediatrics at the Medical University of Warsaw, Poland. They talk about some of the inconsistencies between different medical organizations’ guidelines for pediatric probiotic use, and how clinicians can move forward with recommendations based on the best available evidence.

 

Key topics from this episode:

  • Guidelines exist on probiotic use for gastroenterological issues in children, but there are differences (especially regarding acute gastroenteritis) between guidelines from different medical societies: European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) and The American Gastroenterological Association (AGA).
  • Realistic expectations are necessary when prescribing probiotics. Different probiotics have different benefits, but they are not a ‘magic bullet’. For example, the evidence shows certain probiotics for acute gastroenteritis reduce diarrhea by an average of one day. This could have a big impact on the quality of life of the end user, but for clinicians it may not sound like a lot so they must set expectations accordingly.
  • The market is overflowing with probiotic products, many of which do not have proven efficacy. This makes it difficult for end users and healthcare professionals to distinguish the best products.
  • Always look for evidence-based probiotics with documented efficacy for the indication for which they are intended.
    • Physicians have the ethical duty to prescribe evidence-based products (that is, clinically proven, effective products).
    • The exact strains and doses matter.
  • Formal training and education of healthcare professionals regarding the beneficial effects of microbes, the microbiome, and probiotics are currently lacking.
  • Is it more valuable to know probiotics’ mechanism of action, or to have evidence from clinical trials that they are effective?
    • Ideally we would have both, but since we don’t know the exact mechanism for all probiotics, positive evidence from clinical trials is crucial. 
    • We also need to make clear to healthcare professionals and end users what to expect from taking probiotics. For example, some probiotics reduce the chances of developing antibiotic-associated diarrhea by 50%. For colic, some probiotics can reduce the crying time by half an hour. These are modest benefits but for the affected individual they may be impactful.
  • For vulnerable populations such as preterm infants, we need high-quality products with proven safety and efficacy.

 

Episode abbreviations and links:

 

About Prof. Hania Szajewska

Hania Szajewska, MD, is Professor and Chair of the Department of Paediatrics at the Medical University of Warsaw and the Chair of the Medical Sciences Council. Among her various functions, she served as the Editor-in-Chief of the Journal of Pediatric Gastroenterology and Nutrition; a member of the Council and then as the General Secretary of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN); the Secretary of the ESPGHAN Committee on Nutrition. Most recently, she joined the Board of Directors of the International Scientific Association for Probiotics and Prebiotics (ISAPP). Prof. Szajewska has broad interests in pediatric nutrition but her research focuses on the effects of early nutritional interventions on later outcome; and the gut microbiota modifications such as with various biotics (probiotics, prebiotics, synbiotics, postbiotics). She is or has been actively involved in several European Union-funded research projects. She is an enthusiastic advocate for the practice of evidence-based medicine. Prof. Szajewska has co-authored more than 400 peer-reviewed publications and 30 book chapters. Citations >18,141. Hirsch index 72 (WoS, March 2023).

Questioning the existence of a fetal microbiome, with Dr. Kate Kennedy

Episode 19: Questioning the existence of a fetal microbiome

Questioning the existence of a fetal microbiome, with Dr. Kate Kennedy

 

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.

Questioning the existence of a fetal microbiome, with Dr. Kate Kennedy

Episode summary:

In this episode, the ISAPP podcast hosts tackle the debate on the existence of a fetal microbiome, with guest Kate Kennedy PhD of McMaster University in Canada. They talk about Kennedy’s recent co-first-authored paper in Nature, which concludes that it is not biologically plausible that the fetus harbors live microorganisms, and that previous microbial sequencing studies on the fetal microbiome did not account for the many sources of contamination.

 

Key topics from this episode:

  • During the last 10 years, a lively debate has emerged on whether humans harbor living microorganisms prior to birth. Some scientists have looked at fetal and placental tissues and amniotic fluid, and have ostensibly detected microbial DNA. But those results are being questioned, with the argument that the signals being found are not biologically plausible.
  • Kennedy et al. published an article in Nature that re-analyzed data and brought in experts from different related fields to help interpret the data. The conclusion is that the fetal microbiome does not exist. Previous studies have likely seen contamination during sampling, since it’s nearly impossible to collect samples in a sterile way following vaginal delivery; contamination can happen at different stages so stringent controls are needed across all these areas of potential contamination. Furthermore, live microorganisms in the fetus does not fit with what we already know in related fields of science.
  • The popularity of microbiome research may have made scientists interested in this topic, although sequencing by itself may not be sufficient to settle the question of whether a fetal microbiome exists.
  • Human cells have Mitochondrial DNA, which is bacterial in origin. In 16S rRNA gene sequencing, there is some overlap in what is amplified, and this could include mitochondrial DNA, giving misleading results. This was not accounted for in some of the initial fetal microbiome studies.
  • Bringing together disparate disciplines is inherently challenging. It’s very important to work to understand each other and understand the host and biological situation you’re dealing with.
  • If there were even small numbers of bacteria present in the fetus it would have huge implications for our understanding of fetal biology and immunology. One question would be: how is the fetus limiting growth of any microbes it harbors?
  • Despite the likelihood that the fetal microbiome does not exist, the fetus is not unprepared for the microbial onslaught after birth. The maternal microbiota and immune system can educate the fetus immunologically in the absence of fetal colonization.

 

Episode abbreviations and links:

 

About Dr. Kate Kennedy

Kate completed her PhD on the role of the maternal gut microbiome in perinatal programming in the lab of Dr. Deborah Sloboda at McMaster University. She previously completed her BSc and MSc in Biology at the University of Waterloo. Her research explores host-microbiome relationships in pregnancy, early-life, and aging to understand their role in modulating health and disease risk.  

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

 

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Do antibiotics ‘wipe out’ your gut bacteria?

By Dr. Karen Scott, University of Aberdeen, UK

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

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

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

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

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

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

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

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

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

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

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

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

 

Probiotics, Prebiotics and Globobiotics!

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

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

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

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

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

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

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

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

Prebiotics do better than low FODMAPs diet

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.

 

 

“A healthy woman, a healthy baby, a healthy generation” lessons learned from the 4th Annual Women and their Microbes Conference

By Dr. Mariya Petrova, Microbiome insights and Probiotics Consultancy, Bulgaria

The 4th annual Women and their Microbes conference took place at the beginning of March celebrating the International Women’s day. The first-ever conference outside Europe in Hamilton, Canada brought together top scientists to discuss the importance of women’s health through the prism of women’s specific microbiomes. The theme of the conference was Microbiome Management in Pregnancy with a uniquely designed high-quality program translating the latest research into the clinical setting. I was honored to serve on the organizing committee for this meeting, and I provide highlights below.

Our health starts long before birth. The developing fetus receives information from the mother in the form of hormones and nutrients and uses these to predict the external environment. The fetus then uses this information to adapt its development to better its chances of survival after birth. However, the developing fetus can be “misinformed.” This happens through the maternal factors such as her use of drugs, stress, and diseases such as obesity and asthma. For example, both absolute maternal weight and weight gain during pregnancy affect microbiota development in infants (Carmen Collado et al., 2010). Maternal microbiota can also shape the immune system of the newborns. Therefore, keeping women on the right course before pregnancy and healthy during pregnancy must be a priority. This will later be translated into a healthier life for the infant through adulthood. Many of us associate healthy pregnancy with women taking the right nutrients and minerals such as folic acid, B12 vitamins, and iron and we are not wrong. But microbes also play an essential role in health. Microbes are a crucial factor providing nutrients, immune protection and regulating host physiology. Particular strains of Lactobacillus sp. and Bifidobacteria sp. can produce vitamin B12 and folic acid in the gut (Magnusdottir et al., 2015), which may be very beneficial during pregnancy. Of interest, this production increases when paired with prebiotics. Not only that, but microbes are increasingly recognized as important in reproduction, pregnancy, and development. Fertilization doesn’t happen in a sterile environment. Distinct bacterial communities are present in the female reproductive tract, but semen health and male fertility are also important (Weng et al., 2014). So don’t forget the “Y” in the equation – fathers also play a role in the health of their offspring. Gestational tissue microbes can also play an important role in development. More research is needed to better understand these microbiomes and the extent to which they can be influenced by maternal diet and health state.

What if the things go wrong – adverse pregnancy outcomes. Preterm birth is an ongoing challenge with rates steadily growing and with limited approaches for prevention. It results in 75% of neonatal morbidity and mortality. High numbers (55-80 %) of preterm births are associated with dysbiosis and a shift of the vaginal microbiota towards a more diverse state (Freitas et al., 2018). It seems likely that the vaginal microbiome can protect against adverse pregnancy outcomes. However, it appears that both antibiotics and probiotic therapy used to date are not effective at preventing preterm birth. “How to prevent adverse pregnancy outcomes?” is a million dollar question. We need a highly discriminatory diagnostic test that defines versions of ‘abnormal’ vaginal microbiomes. This test needs to be significantly associated with adverse health outcomes. The type of abnormal profile that results in preterm birth needs to be distinguishable from other possible ‘abnormal’ profiles. Such a diagnostic tool needs to be simple enough for a clinical environment and cost-effective. We need to have a safe intervention that can ‘treat’ or normalize a microbiome ideally preconception or early pregnancy.

Where do probiotics fit? Probiotics and prebiotics can enhance the nutrient status of the mother via increasing micronutrient and mineral absorption. During pregnancy, about 3.6% of North American women, 14% of The Netherlands women and 23% of Australian women consume probiotics. A lot of studies focus on the role of probiotics for preventing Group B Streptococcus infections, maternal obesities, postpartum depression, and mastitis. Although results are promising, more studies are needed to make clear conclusions and select the best strains for each condition. Importantly, currently used probiotics do not appear to pose safety concerns for pregnant and lactating women. Nevertheless, consumers’ knowledge regarding probiotics is not very precise. This confusion often may stem from a probiotic market with many different manufacturers, some of which are not legitimate, selling products that are not well defined, with very little clinical evidence. A major effort in educating clinicians, pharmacists and the consumers has been made by creating probiotic guidelines. Dragana Skokovic Sunjic has been working in the last ten years in publishing and updating the “probiotic chart.” The probiotic chart summarizes commercially available probiotic supplements or foods sold in Canada or the USA that have published clinical evidence for the particular strain(s) present in each product. Of note, for products containing multiple strains, evidence must be provided for the specified combination and not extrapolated from the evidence for the separate probiotic strains. At present these guidelines are used by primary care providers, specialists (pediatrics, GI), academic teaching hospitals, universities and others.

With the increasing number of microbiome studies, we are witnessing a paradigm shift in the scientific literature with more people focusing on the importance of microbes in human health. Women’s health is a cornerstone for successful reproduction, with important implications for the health of the next generation. Initiatives such as Women and their Microbes are crucial to link the science and medicine together to bring awareness within the healthcare and academic community.

The Children of Masiphumelele Township

Gregor Reid PhD MBA FCAHS FRSC, Professor, Western University and Scientist, Lawson Health Research Institute, London, Canada

Just off the main road from Cape Town, South Africa to Simon’s Town, sits Masiphumelele township where challenges of poverty, malnutrition, HIV and the risk of violence face people every day.

It is also the location for the Desmond Tutu HIV Foundation Youth Centre, a safe haven that provides adolescent-friendly sexual and reproductive health services alongside educational and recreational activities for youth living in Masiphumelele and surrounding areas.

To understand some of the dangers that children face, in 2017, about 270,000 people in South Africa were newly infected with HIV, adding to one of the highest HIV prevalence rates in the world. The Tutu Youth Centre aims at helping educate youth to reduce their risk of becoming another HIV statistic.

I was invited there by University of Cape Town Professor Jo-Ann Passmore, a woman not only recognized for her research but whose passion for helping others is reflected in her warm smile (4th from left in group photo). She asked if I would be interested in holding a workshop to illustrate to the youth how using sachets of probiotic bacteria could empower them. I jumped at the chance. On an afternoon break from the Keystone Symposium, thirty researchers joined me along with Jo-Ann and my wife Debbie, a teacher of children with learning disabilities.

After a tour of the areas where children learn on computers, play games in safety, or have personal discussions about sexual health, everyone filled the room with a stunning backdrop of the Nobel Laureate’s image. Having been privileged to meet the Archbishop when he was hosted by St. Joseph’s Healthcare Foundation in 2008, it was a nerve-tingling experience for me.

Giving a lecture on beneficial microbes is hard enough to peers sitting in the back of the room, but to do so with young South Africans was more somewhat daunting. However, it proved to be a lot of fun especially when we had to identify kids who were good leaders (the boys all pointed to a girl), who liked to make stuff and sell it to others (two boys stood out). By the end, we had picked the ‘staff’ of a new company.

The next step was for four groups to decide on the company’s name, what products they’d make from the probiotic sachets (the options were many including yoghurt, cereals, fruit juices, maize), what marketing tools they would use and who they would target to obtain a respectable income.

Interestingly, several of the conference participants seemed less engaged, as if they had never considered how microbiology research could affect real lives. In front of them were children facing huge challenges on a day-to-day basis. In one group, the kids were quiet until my wife brought out pens and paper, then they went to town designing products, names and labels. A lesson for me on how different people need different stimuli to become engaged. The faculty left early to beat the traffic back to Cape Town, so unfortunately, they did not hear the outcome of the children’s work.

When we re-assembled to present the results, I was impressed with what could be created in such a short time. My favourite was the Amazing Maize, a bottle shaped like a corn cob with the idea it would contain fermented maize. It emphasized the importance of marketing and for products to taste and look good to be purchased.

It has been over ten years since Archbishop Tutu applauded us for the Western Heads East project and thanked us for empowering women and youth and contributing to nutrition in Africa. Since then, thanks to the huge efforts of Western staff and students, and more recently IDRC funding and partnerships especially with Yoba-for-life, Heifer International and Jomo Kenyatta University of Agriculture and Technology, over 260,000 people in east Africa are now consuming probiotic yoghurt every week. The children of the South African townships were maybe too young to join in this new wave of microenterprises, but at least now they have heard about it and the importance of fermented food and beneficial bacteria.

In the background of the workshop several wonderful women committed to start up a new production unit using the Yoba/Fiti sachets developed by Yoba-for-life. I left them some sachets for them to try out the process.

But it was me who left with the biggest lesson on how precious each life is, and how those of us with the knowledge, need to provide the means for others to use their own talents to fulfill the purposes of their lives.

No better way than to start with the children.

rdamicrobes

Recommended daily allowance (RDA) for microbes?

By Prof. Colin Hill, Alimentary Pharmabiotic Centre, Food for Health Ireland, University College Cork

In this months’ issue of The Biochemist (August 2018) I explored the concept of whether or not there could be a health benefit to ingesting large numbers of safe microbes in our diet (see the open access article here).  This was an effort, though I should stress not a scientifically rigorous effort, to consider the long history of encounters between humans and ingested microbes.

This opinion piece was prompted by a series of open questions which have often puzzled me.  Why is so much of our immune system focussed on the gut?  Why not simply let the microbes and food constituents pass through and get digested without such strict surveillance?  Surely it would be more metabolically favourable to only react to those microbes that breach our epithelial barriers?  Why does our enteric nervous system devote so much of its resources to the gut?  Why is there a generally beneficial effect of many probiotics across so many health conditions?  Why is mother’s milk designed to promote the growth of microbes?

Could the solution to all of these questions be down to a very simple answer? Because the gut ‘expects and requires’ constant encounters with microbes for full functionality. Given that humans evolved into a microbial world, and that we have consumed a diet rich in microbes for most of our evolutionary history, it makes sense that our enteric systems would be designed to appropriately deal with microbes of all types, selecting out those which can cause damage and destroying them, accommodating those which will become part of our microbiomes and letting the rest pass through.  Surely we are monitoring and controlling our ‘microbial’ organ in the same way that our eukaryotic organs are monitored and controlled.

Could it be that the rise in autoimmune diseases could be, at least in part, due to an immune system primed to expect more microbes than it currently sees?  Should we recommend that a daily dose of safe microbes should be included in dietary guidelines – in the form of more safe raw foods, more fermented foods and more probiotics? It must be emphasized that some serious pathogens must be controlled or eliminated from food – not ALL live microbes are safe. But the goal can be to process only when needed for safety reasons, so foods can be a source of the safe microbes they harbour.

Lots of questions, and not many answers.  But I for one am taking account of this concept in my daily diet and am deliberately eating more microbes – I’ll let you know how it goes!

East meets West at ISAPP’s first meeting in Asia

By Mary Ellen Sanders, PhD

The International Scientific Association for Probiotics and Prebiotics (ISAPP) recently convened its first meeting held in Asia, with the modern hub of Singapore as a host city. The meeting featured a two-day open registration meeting, attended by nearly 250 scientists, health professionals, and industry representatives, and a third day of smaller discussion groups by invitation. The meeting provided a rare opportunity for non-members to attend. It provided a dynamic forum for sharing different clinical experiences and regulatory nuances amongst the continents, as well as allowing attendees to better appreciate the research being performed in the Asian region.

Here are a few speaker highlights:

 

Mimi Tang MD

Tang presented the results of a double-blind, randomized controlled trial examining the effect of probiotic supplementation combined with oral immunotherapy (OIT) to decrease the risk of peanut allergy in children. Peanut allergy is one of the fastest growing food allergies in children. In the Probiotic and Peanut Oral ImmunoTherapy [PPOIT] study, children randomized to the intervention group had increased rates of sustained responsiveness to peanut several weeks after discontinuation of the treatment. Tang discussed the implications of the study, as well as current, larger clinical trials that are building upon these findings.

 

Dr. Bruno Pot

The Lactobacillus genus is taxonomically abnormally heterogeneous. Currently, the 231 Lactobacillus species range from a genome size of 1.23 – 4.91 megabases, have a GC content of 32-57% and an average nucleotide identity that is typical for a family or worse. Such ranges are far beyond what is acceptable for a bacterial genus. Experts are recommending that the current genus should be split into 12 new genera. Some well-known lactobacilli would be re-named, which may have important repercussions commercially and legally.

 

Profs. Colin Hill and Patrice Cani

Hill described how lactase in yogurt cultures improves lactose digestion; he emphasized how mechanisms that drive probiotic activity are complex. Some scientists are searching for a single molecule that drives probiotic health benefits—but it is unlikely to be found.

Hill noted even inactivated (non-living) microbes may have health effects—for example, a study showed that a dead Lactobacillus strain reduced anxious behavior, reduced cortisol levels, and impacted the microbiome in a mouse model. Work by Prof. Patrice Cani showed that heat-killed Akkermansia muciniphila were sufficient to ameliorate obesity and diabetes in mice. Does this suggest that we will need to start quantifying probiotics based on biomass as well as CFU?

 

Profs. Hani El-Nezami, Gregor Reid and Akihito Endo

These three speakers illustrated the important impact of environmental toxins (extremely potent aflatoxins, pesticides, and heavy metals) on humans and wildlife. They showed how certain probiotic strains can decrease aflatoxin absorption and even degrade them; sequester heavy metals and pesticides to reduce their uptake; and enhance resistance to honey bee colony collapse disorder that threatens the world’s food supply.

 

Prof. Wim Teughels

To date, 11 studies have been published on probiotics with a low ‘number needed to treat’ for prevention of dental caries in infants, toddlers, and adults. One study showed the benefits of administered L. reuteri, following children for nine years after they were treated as infants before any teeth had emerged. Also, data exist for probiotics influencing other oral health endpoints, including periodontal infections, oral candida infections, and halitosis.

 

The discussion groups on day three of the conference addressed a range of topics:

  • Possibilities to harmonize global probiotic and prebiotic regulations—Chaired by Seppo Salminen (Finland), Yuan Kun Lee (Singapore), and Gabriel Vinderola (Argentina)
  • Fermented foods for health: East meets West—Chaired by Bob Hutkins (USA), Paul Cotter (Ireland), and Liu Shao Quan (Singapore)
  • Potential value of probiotics and prebiotics to treat or prevent serious medical issues in developing countries—Chaired by Daniel Merenstein (USA), Reuben Wong (Singapore), and Colin Hill (Ireland)
  • Prebiotics as ingredients: How foods, fibres and delivery methods influence functionality—Chaired by Glenn Gibson (England) and Karen Scott (Scotland)

 

These workshops often produce peer-reviewed publications based on the discussion outcomes, so stay tuned for these developments. (See here for a list of ISAPP publications.)

The full meeting report is being developed and will be posted on the ISAPP website shortly.

The 2019 meeting will return to ISAPP’s normal format, hosted by Dr. Sarah Lebeer in Antwerp, Belgium.

 

blog foodomics image

Global FoodOmics: A Crowd-Sourced Window Into Microbes In Our Foods

January 25, 2018. By Mary Ellen Sanders, PhD , Dairy & Food Culture Technologies

Among the factors under our control, diet may be the most important determinant of our gut microbiota. Observations from the American Gut Project suggest that foods containing live microbes increase fecal bacterial diversity, which is generally associated with a healthy gut.

An initiative, Global FoodOmics, was launched earlier this year at the University of California San Diego under the auspices of the American Gut Project to learn more about bacteria in foods and the small molecules they produce. Dr. Julia Gauglitz is the project manager. Food samples (over 2000 have been collected to date) have been analyzed for their small molecule composition and will be tested by 16S rDNA sequencing to determine the bacterial species present. Although currently in its early stages, the aim for this project is to inventory the vast different foods consumed by people around the world.

Although many fermented foods (beer, bread, wine, kefir, many cheeses and others) rely on yeast or molds as fermentation or ripening agents, this project will aim to detect bacterial DNA, but these DNA approaches cannot distinguish between life and dead bacteria.  Labels and other descriptors accompanying submitted food samples may help determine if the species detected are likely to be alive. Fermented foods that retain live bacteria are more likely to influence our colonizing microbiota.

The small molecules being assayed are not limited to the ones produced by microbes. They may be due to microbial growth in the food (by food fermentation microbes or perhaps by spoilage or food poisoning microbes), may be innate to the food, or may be intentional or incidental (e.g., pesticides) additives to foods.

The intent is to turn Global FoodOmics into a crowd-sourced project. It will join the American Gut Project as an avenue for citizens to directly participate in science and enable the project to make all of the data publically available to other researchers and clinicians.

It is notable that this project is not the first attempt to understand the microbial components of food. Food microbiologists for decades have been assaying foods for microbes used to produce food, responsible for food spoilage and linked to food poisonings.  Recently, Prof. Bob Hutkins, University of Nebraska, on behalf of the International Scientific Association for Probiotics and Prebiotics (ISAPP) and with support from the National Dairy Council, embarked on a project to learn the state of knowledge about levels of live microbes in fermented foods. They dug into the published literature and emerged with “A survey of live microorganisms in fermented foods”, In Press at Food Microbiology. This paper gives us a summary of what is known about populations of live microbes in fermented foods, information that is very useful for people wanting to add live microbes to their diet.

Another effort to understand microbes in foods is the Consortium for Sequencing the Food Supply Chain, a partnership between IBM Research and Mars Inc. This project, focused on food safety, aims to develop a baseline of normal microbial communities in foods.

Both Global FoodOmics and the Consortium for Sequencing the Food Supply Chain will leverage modern DNA sequencing technologies to allow us better understand the microbes associated with foods. Global FoodOmics is the first project to understand the microbes and molecules in foods, by pairing small molecule metabolomics measurements with rDNA sequencing.