How the maternal microbiome influences offspring neurodevelopment, with Dr. Eldin Jašarević PhD

/in Podcast, Season Three /by Laura

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This episode features Dr. Eldin Jašarević PhD from University of Pittsburgh discussing research that investigates how maternal signals influence the general development and neurodevelopment of the offspring. Dr. Jašarević’s particular interest in this field stems from his family’s journey as refugees from Bosnia who found their way to the US. His lab studies how maternal stress or diet signals the developing brain to facilitate a lasting change, focusing on the role of the gut and vaginal microbiomes. His work in mouse models has shown that even mild stressors early in pregnancy trigger a gut microbiome change that lasts, but the challenge is to figure out whether the microbiome is responsible for the lasting effect. More human intervention studies are needed to understand how these findings may benefit pregnant women and the eventual development of their children. Regarding brain development, germ-free mice have brains that grow and develop differently from mice with an intact microbiome: for example, microbial metabolites are involved in key epigenetic processes for the brain. In general, the field may be moving toward understanding host-microbial interactions and dispersal of microbial-derived metabolites in pre-conception health and fertility, to eventually enable earlier intervention.

Episode abbreviations and links:

About Dr. Eldin Jašarević PhD:

Eldin Jašarević is an Assistant Professor in the Departments of Obstetrics, Gynecology and Reproductive Sciences and Computational and Systems Biology at the University of Pittsburgh, and a Principal Investigator at Magee-Womens Research Institute. He received his Ph.D. in Neuroscience from the University of Missouri, where he worked at the Thompson Center for Autism and Neurodevelopmental Disorders. His predoctoral research focused on the role of maternal lifetime experiences on brain development. During his postdoctoral fellowship with Dr. Tracy Bale at the University of Pennsylvania, Eldin defined mechanisms by which disease susceptibility can be transferred across generations via the microbiome. His current research focuses on understanding how microbial-derived signals act as regulators of development, with particular emphasis on the germline. His contributions to the field have been recognized through his selection as a Kavli Fellow of the National Academy of Sciences, a Burroughs Wellcome Fellow, and through research funding from NIMH, NICHD, and NIDDK.

Fiber and short-chain fatty acids for cognitive health, with Dr. Boushra Dalile PhD

/in Podcast, Season Three /by Laura

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This episode features Dr. Boushra Dalile PhD from KU Leuven in Belgium – ISAPP’s 2024 Glenn Gibson Early Career Researcher Award winner – discussing the protective role of fiber and prebiotics on cognitive health. Dr. Dalile is trained in psychology, and in her current work she undertakes human intervention studies to examine the effects of interventions using fibers, prebiotic fibers, and / or short-chain fatty acids on human stress- and anxiety- related processes. Fermentable fibers in the diet are known to result in the production of short-chain fatty acids (SCFAs), and she has been involved in studies in which participants receive the SCFAs directly. Interestingly, sufficient SCFAs circulating in the blood are required for protection against a stressor, regardless of any intervention. Dr. Dalile explains that cognitive deterioration may start 20 to 30 years before the first symptoms occur in later life, so that prevention (or “cognitive resilience”) is the most promising strategy. So far, the best recommendation is to maintain a fiber-rich diet throughout adulthood, although various research groups are working to find out whether a specific intervention could be effective for protecting cognition. This episode is the first of a series on the microbiota-gut-brain axis.

Episode abbreviations and links:

Additional resources:

ISAPP blog post: Can we estimate prebiotic effects from short-chain fatty acid production?

About Dr. Boushra Dalile PhD:

Dr. Boushra Dalile PhD is a Postdoctoral Researcher at the Laboratory of Biological Psychology at KU Leuven, Belgium. She was trained in psychology (Swinburne University of Technology, Australia) and cognitive neuroscience (University of Skövde, Sweden; The Max Planck Institute for Human Cognitive and Brain Sciences, Germany), before being awarded a PhD in Biomedical Sciences in 2021 at the Translational Research Center for Gastrointestinal Disorders at KU Leuven under supervision of Prof. Kristin Verbeke. Since her PhD, she investigates the effects of dietary fiber and the role of short-chain fatty acids (SCFAs) on stress and anxiety, and is currently mapping out their putative mechanisms of action in humans. Her latest research seeks to harness butyrate’s neuro-psychopharmacological potential in modulating learning and memory to advance translational research on anxiety and help shape treatment options and dietary recommendations. Her work was published in Nature Reviews Gastroenterology & Hepatology, The Lancet Planetary Health, Neuropsychopharmacology, and Psychoneuroendocrinology.

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

/in Podcast, Season Three /by Laura

 

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

Key topics from this episode:

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

Episode links:

Additional resources:

About Prof. Kelly Swanson:

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

Developing probiotics to prevent white nose syndrome in bats, with Prof. Ann Cheeptham PhD

/in Podcast, Season Three /by Laura

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This episode features Prof. Naowarat (Ann) Cheeptham, a cave microbiologist from Thompson Rivers University (Canada), speaking about a fungal infection in bats that causes white nose syndrome. She and her collaborators are looking at the microbiomes of the bats and their environments for possible ways to prevent this serious infection. White nose syndrome is caused by Pseudogymnoascus destructans infecting bats in hibernation and causing them to act in unnatural ways. The condition has caused massive death of bats in North America, although not in other regions of the world with the same fungus. Dr. Cheeptham and colleagues are looking for strategies to prevent white nose syndrome. Initially they screened environmental bacteria with activity against the fungus, but had difficulty knowing how to apply these bacteria to the bats. Their current approach is to take four bacterial strains isolated from healthy bats and apply them in bat boxes so they may become established on the vulnerable bats to prevent white nose syndrome. The preventative actions of the bacteria are still under investigation, but the collaborators believe the mechanism is related to metabolite production. This episode is part of a series on the role of biotics in animal health.

Episode abbreviations and links:

About Prof. Ann Cheeptham PhD:

Dr. Cheeptham is a professor at the Department of Biological Sciences, Thompson Rivers University, Kamloops, British Columbia, Canada. Her research interests include cave microbiomes/new drug discovery, white-nose syndrome in bats, alternative treatment tools against multidrug-resistant infections, and geomicrobiology.  Her work has fortunately been featured in the New York Times, WIRED, Bloomberg TV network’s Spark series, Al Jazeera TV, the CBC’s Nature of Things (The Antibiotic Hunters episode), Global TV (Global 16×9 and Global Health), Knowledge Network, CBC radio (Daybreak) and in several International and Canadian magazines.  Besides her passion for cave microbiology and research, she is also drawn to pedagogical issues in microbiology education. Recently, she has been the recipient of the 2022 3M National Teaching Fellowship from the Society for Teaching and Learning in Higher Education (STLHE) and 3M, the 2020 TRU Faculty Excellence Award, and the 2020 D2L Innovation Award in Teaching and Learning STLHE and D2L (Desire2Learn).

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

/in Podcast, Season Three /by Laura

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

Episode abbreviations and links:

Additional resources:

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

About Prof. Alex Hristov PhD:

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

Archive Highlight: Prebiotics for animal health, with Prof. George Fahey

/in Podcast, Season Three /by Laura

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Continuing our series on the role of biotics in animal health, we are highlighting Episode 5 from our archives. This episode features a former ISAPP board member, Prof. George Fahey, giving an overview of animal prebiotic research and describing future opportunities for prebiotics in animal nutrition. Prof. George Fahey is a prominent animal nutrition scientist who is currently Professor Emeritus at University of Illinois. Fahey explains how animal nutrition research relates to human nutrition research, and the changes in the field he has seen over the course of his long career. He describes the research on prebiotics for animal nutrition, covering both livestock and companion animals.

Key topics from this episode:

  • A short history of animal prebiotics research as well as future opportunities in animal nutrition.
  • Pro- and prebiotics are being explored as an alternative to antibiotic treatment in production animals. Antibiotics are overused, leading to an increase in antibiotic resistance; the “biotics” therefore have great potential in animal nutrition.
  • Probiotics can potentially be used instead of antibiotics to inhibit pathogens and support the gut microbiota in animals.
  • Prebiotics possibly have high nutritional value and beneficial effects in animals, especially in poultry and pigs.
  • There are limitations to using prebiotics in the animal industry, especially for some animals such as horses and ruminants.
  • There has been increased use of prebiotics for companion animals (pets) in the past few years. Now many pet foods contain prebiotics.
  • Benefits of using prebiotics in companion animals:
    •  Support digestive health
    •  Improve stool quality
    • Support the gut microbiota, which also translates to good stool quality
  • A short overview of how companion animals’ food is produced, and the timing of adding prebiotics.
  • Wild animals’ diet has low nutrition with limited to no prebiotic intake, resulting in a shorter lifespan in comparison with companion animals
  • Some take-home points from animal models and animal nutrition research.

 

Episode links:

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics
The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic

 

Additional resources:

Are prebiotics good for dogs and cats? An animal gut health expert explains. ISAPP blog post
Using probiotics to support digestive health for dogs. ISAPP blog post
Prebiotics. ISAPP infographic

 

About Prof. George Fahey:

George C. Fahey, Jr. is Professor Emeritus of Animal Sciences and Nutritional Sciences at the University of Illinois at Urbana-Champaign. He served on the faculty since 1976 and held research, teaching, and administrative appointments. His research was in the area of carbohydrate nutrition of animals and humans. He published numerous books, book chapters, journal articles, and research abstracts.

He currently serves on two editorial boards, numerous GRAS expert panels, and is scientific advisor to both industry and governmental organizations. He retired from the University in 2010 but continues to serve on graduate student committees and departmental search committees. He owns Fahey Nutrition Consulting, Inc. that provides services to the human and pet food industries.

Understanding the gut microbiome in dogs and other pets, with Prof. Jan Suchodolski DACVM PhD

/in Podcast, Season Three /by Laura

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This episode features Prof. Jan Suchodolski DACVM PhD from Texas A&M University, discussing the gut microbiome in dogs and other companion animals as part of our series on the role of biotics in animal health. Prof. Suchodolski’s lab focuses on understanding gastrointestinal (GI) diseases in pets and developing diagnostic tests for research and clinical practice. His lab works on building a model of what’s happening with animal health, combining microbiome measures with measures of host health. For example, they found that severe gut microbiome dysbiosis in dogs reflected a greater extent of mucosal damage, contributing to the big picture of GI disease. Certain microbiome features when combined with metabolites are promising biomarkers of GI disease in pets. Test reproducibility is highly important, and treatment tends to be multi-modal. Prof. Suchodolski cautions against direct-to-consumer pet microbiome tests, noting that unvalidated assays are very common.

Episode abbreviations and links:

Additional resources:

ISAPP infographic: Prebiotics and probiotics for pets

ISAPP blog post: Are prebiotics good for dogs and cats? An animal gut health expert explains

ISAPP blog post: Using probiotics to support digestive health for dogs

About Prof. Jan Suchodolski DACVM PhD:

Jan S. Suchodolski is a professor, Purina PetCare Endowed Chair for Microbiome Research, associate director and head of microbiome sciences at the Gastrointestinal Laboratory at Texas A&M University. He received his DrVetMed from the University Vienna, Austria and his PhD in veterinary microbiology from Texas A&M University. He is board certified in immunology by the American College of Veterinary Microbiologists (ACVM). His research is focused on developing biomarkers for gastrointestinal disease and therapeutic approaches for the modulation of the intestinal microbiota. He has authored or co-authored more than 400 peer-reviewed articles in the area of veterinary gastroenterology and microbiome research. In 2024, he received the AVMA career achievement in canine research award.

Biotics for agricultural animals, with Prof. Steve Ricke PhD

/in Podcast, Season Three /by Laura

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This episode, part of a series on the role of biotics in animal health, is a broad-ranging conversation on biotics for agricultural animals, with Prof. Steve Ricke PhD from University of Wisconsin-Madison. Prof. Ricke explains some of the different applications of biotics for poultry as well as swine and ruminants: rapid growth, efficient use of feed, and reducing inflammation. Biotics may also have a role in food safety as it relates to agricultural animals, with research showing how microbiome diversity shapes the impact of pathogens. Animal genetics, diet, and microbiome interactions are extremely complex and fortunately the tools to study these interactions have improved in the past several decades. Prof. Ricke urges scientists to take into account the microbial ecology surrounding the animal – and not to forget the potential impact of the animal on its environment.

Episode abbreviations and links:

Additional resources:

ISAPP podcast with Prof. George Fahey PhD, a mentor of Prof. Ricke: Prebiotics for animal health

About Prof. Steve Ricke PhD:

Prof. Steven C. Ricke received his B.S. and M.S. from the Univ. of Illinois, Champaign-Urbana, IL. and Ph.D. from the Univ. of Wisconsin, Madison, WI. Prof. Ricke was a USDA-ARS postdoctorate in the Microbiology Department at North Carolina State Univ. then joined Texas A&M Univ. as a professor in the Poultry Science Dept.  In 2005, he became the first holder of the new Donald “Buddy” Wray Endowed Chair in Food Safety and Director of the Center for Food Safety at the University of Arkansas (UA) and was a faculty member of the Dept. of Food Science and Cellular/ Molecular Graduate program. In 2020 he became the Director of the Meat Science and Animal Biologics Discovery Program in the Animal and Dairy Sciences Dept. at the University of Wisconsin-Madison. Prof. Ricke’s lab conducts studies on the growth, survival, and pathogenesis of pathogens in the poultry gut and their interactions with gut microbiota.

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

/in Podcast, Season Three /by Laura

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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 37: Targeting the gut microbiome in inflammatory bowel disease, with Prof. Harry Sokol MD PhD

/in Podcast, Season Three /by Laura

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The ISAPP hosts discuss the microbiome in inflammatory bowel disease (IBD) with leading expert Prof. Harry Sokol MD PhD, who is Professor of Gastroenterology at Saint Antoine Hospital and has positions with Sorbonne University and the Micalis Institute, INRAE in Paris, France. Sokol talks about the specific gut bacteria that seem to be important in IBD, as well as the challenge of targeting the gut microbiome for therapeutic effects.

Key topics from this episode:

  • Dr. Sokol says that while more and more gastroenterologists see the gut microbiome as relevant to disease diagnosis, prognosis, and treatment, the microbiome is not yet an important part of clinical practice. Fecal microbiota transplantation is widely used for recurrent C. difficile infection, but its utility in chronic disease is not established.
  • Earlier in his research career, he started with the ‘global description’ strategy of surveying the gut microbiome of patients with IBD using the available scientific tools. More recently, Dr. Sokol has focused on ‘candidate microorganisms’ to target such as Faecalibacterium prausnitzii, or F. prau.
  • How do scientists know F. prau is important for IBD? First, those with IBD have less of these bacteria. And patients with Crohn’s disease who have the lowest amounts in their gut microbiomes have the highest chance of disease relapse. Furthermore, these bacteria are human-specific and are found at a very high prevalence in healthy individuals – it makes up between 5 and 10% of the average person’s gut microbiome. A recent prospective study (GEM) also found that F. prau was one of the bacterial species that decreased even before the onset of inflammation and disease. Now Dr. Sokol and others are exploring the therapeutic uses of these bacteria.
  • The ultimate goal with IBD is to use treatments that target the microbiome alongside treatments that target the host.
  • A decrease in F. prau within the gut microbiome is not specific to IBD; it’s also seen in people with IBS and diarrhea. These bacteria may have multiple effects in the body.
  • Dr. Sokol’s group worked on CARD9, an IBD susceptibility gene. The gene’s effect on phenotype occurs through the microbiome, because in mice, fecal microbiota transplantation (FMT) was enough to transfer the susceptibility to colitis. The microbiota also transferred an immune defect in IL-22 production, related to an alteration in tryptophan metabolism in the microbiome. Normally some bacteria in the microbiota use tryptophan to produce indoles, which lead to the production of IL-22, but this process was altered in the mice that received the FMT.
  • This tryptophan metabolism in the microbiome is altered in IBD as well as other diseases. It’s one of the major functions of the gut microbiome, similar to short-chain fatty acid production and bile acid metabolism.
  • As for F. prau, challenges remain with growing and scaling up production for industrial use, but currently Dr. Sokol and collaborators have a method that works. Perhaps eventually they will zone in on the molecules produced by the bacteria, but then again the bacteria may be more effective because it may address different mechanisms of action and different targets simultaneously.

Episode abbreviations and links:

Additional resources:

About Prof. Harry Sokol MD PhD:

Harry Sokol is Professor in the Gastroenterology department of Saint-Antoine Hospital (APHP, Sorbonne Université, Paris, France). the co-director of the Microbiota, Gut & Inflammation team (INSERM CRSA UMRS 938, Sorbonne Université, Paris), group leader in Micalis institute (INRAE) and coordinator of the “Paris Center for Microbiome Medicine” (www.fhu-pacemm.fr/). He is an internationally recognized expert in the inflammatory bowel disease (IBD) and gut microbiota fields, in which he has published more than 330 papers in major journals. He is the current president of the French group of Fecal Microbiota Transplantation, and the head of the APHP Fecal Microbiota Transplantation Center. His work on the role of gut microbiota in IBD pathogenesis led to landmark papers, including the identification of the pivotal role of the commensal bacteria Faecalibacterium prausnitzii in gut homeostasis and IBD. Currently, his work focuses on deciphering gut microbiota–host interactions in health and disease to better understand their role in pathogenesis and develop innovative treatments. Harry received two grants from the European Research Council (ERC) in 2016 and 2022, and he is a member of the International Organization for the Study of IBD (IOIBD). Since 2020, he is recognized as a Highly Cited Researcher (Clarivate, Web of Science). Harry Sokol is currently Associate Editor for Gastroenterology. Harry Sokol co-founded Exeliom biosciences (https://www.exeliombio.com/).

Find Harry on X/Twitter: @h_sokol

Episode 36: Uncovering the mechanisms of sorbitol intolerance, with Dr. Jee-Yon Lee MD PhD

/in Podcast, Season Three /by Laura

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This episode features Jee-Yon Lee MD PhD, assistant project scientist at the University of California Davis, USA, speaking about a recent paper on the mechanisms of sorbitol intolerance and the contributions of the gut microbiota. Dr. Lee explains how gut microbes in the large intestine can drive sorbitol intolerance, and how their research group designed a probiotic intervention to ameliorate it in a mouse model.

Key topics from this episode:

  • Dr. Lee joined Baumler lab in 2017 to study how ecological causes such as diet or chronic disease can change host cell metabolism, thereby changing the gut microbiota, and also the effect of the gut microbiota on chronic diseases.
  • Sorbitol is a sugar alcohol used as an artificial sweetener. It cannot be absorbed or catabolized in the small intestine so it reaches the large intestine and draws water into the lumen through osmosis. Large amounts cause diarrhea, but normally small amounts do not. 
  • Some people are sensitive to small amounts of sorbitol and are said to have sorbitol intolerance. Where does the intolerance originate? Possibly the inability of bacteria in the large intestine to catabolize sorbitol using enzymes.
  • Sorbitol intolerance (causing diarrhea) can be transient, such as after taking antibiotics. 
  • What is happening in sustained sorbitol intolerance? Clinically, a recent history of taking antibiotics plus a high-fat diet is associated with diarrhea as well as low-grade inflammation. A mouse model showed that a high-fat diet plus antibiotics led to low-grade inflammation, which may be at the root of sorbitol intolerance.
  • Clostridia are the main bacteria catabolizing sorbitol in the gut. Overall, a high-fat diet plus antibiotics together drive the gut ‘dysbiosis’, and contribute to the chronic depletion of mitochondrial function in the colonic epithelium. This makes the colonic environment less hypoxic, sustains the depletion of Clostridia, and thereby induces sorbitol intolerance.
  • From this, Dr. Lee helped design a probiotic intervention. They selected 3 strains of bacteria and tested them with the high-fat diet and antibiotics mouse model. All of them protected the host from sorbitol intolerance in slightly different ways.
  • Decreased sorbitol dehydrogenase activity may be a biomarker of sorbitol intolerance; currently there’s no way to diagnose this intolerance clinically, so patients typically cut out the substance to discover their intolerance.

Episode abbreviations and links:

About Dr. Jee-Yon Lee MD PhD:

Jee-Yon Lee is an Assistant Project Scientist in Dr. Andreas Baumler’s lab at UC Davis, focusing on studying host-microbial interactions and their impact on human health and non-communicable diseases. She earned her MD and PhD from Yonsei University College of Medicine and served as a family medicine physician in South Korea until 2017. She joined Dr. Andreas Baumler’s lab in 2017 as a visiting scholar and completed her postdoctoral research there. Dr. Lee’s long-term research goal is to elucidate the ecological causes of dysbiosis, its consequences on the development of human diseases, and to find potential therapeutics targeting the microbiome.

Episode 35: Investigating gut microbiome links to chronic diseases, with Dr. Purna Kashyap MBBS

/in Podcast, Season Three /by Laura

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In this episode, the ISAPP hosts discuss the gut microbiome’s role in chronic diseases with Dr. Purna Kashyap MBBS, from Mayo Clinic in Rochester, Minnesota, USA. Dr. Kashyap talks about how to discover the complex factors that trigger and perpetuate chronic diseases such as inflammatory bowel disease, zeroing in on the gut microbiome as a contributor to different aspects of gastrointestinal (GI) tract physiology.

Key topics from this episode:

  • Dr. Kashyap became interested in some of the initial studies linking the gut microbiome to chronic diseases around 2007-2008, and subsequently began to study the molecular mechanisms that underlie changes in GI tract physiology.
  • How can scientists figure out causality in chronic diseases and the role of gut microbes? Dr. Kashyap sees causality as an ongoing cascade of events in the GI tract, with no single causal factor. Both the initial triggers and the perpetuating factors can be considered part of what causes these diseases.
  • Microbes can help perpetuate a certain state in the host because once they establish themselves they serve to make the environment more conducive to their survival. In chronic diseases, the factor that triggers the microbial community configuration may not be as important as the factor(s) that perpetuate it on an ongoing basis.
  • The gut microbiome is changeable but not easy to change. Scientists need to know how the microbial community sustains itself and intervene there to change the community.
  • Even small microbiome studies can be informative if you look at who responds to the intervention and why. This information can be valuable for informing which treatments might work for which subgroups of people.
  • Dr. Kashyap encourages combining three types of research: large-scale studies on microbial metabolites and potential drug targets; clinical studies on the metabolites present in various subgroups; preclinical models studying the effects of individual metabolites.
  • Diet, microbes, and host uptake all contribute to the physiological effects of different metabolites. And for example, if a metabolite is low, knowing which microbes are present is not enough information to explain why it’s low.
  • In gastroenterology, clinicians primarily care about the gut microbiome in relation to the new treatments it makes possible. Now that FDA-approved treatments exist (standardized fecal microbiota transplants for recurrent C. difficile), clinicians may start paying more attention.
  • Does Dr. Kashyap recommend interventions to patients based on their gut microbiomes? A high-fiber diet is good for the gut microbiome and also for overall health, so he advises patients to adhere to dietary recommendations for their daily fiber intake.

Episode abbreviations and links:

Additional resources:

Why researchers need to understand more about the small intestinal microbiome. ISAPP blog.

About Dr. Purna Kashyap:

Dr. Purna Kashyap is practicing gastroenterologist and Professor of Medicine and Physiology, the Bernard and Edith Waterman Director of the Microbiome program, and Director of the germ-free mouse facility in the Center for Individualized Medicine at Mayo Clinic, Rochester, MN. The NIH funded Gut Microbiome laboratory led by Dr. Kashyap is focused on delineating the complex interactions between diet, gut microbiome, and host gastrointestinal physiology.  The laboratory uses germ-free mouse models in conjunction with measures of gastrointestinal physiology in vitro and in vivo to investigate effects of gut microbial products on host gastrointestinal function. In parallel, they use a systems approach incorporating multi-omics, patient metadata, and physiologic tissue responses in human studies, to aid in discovery of novel microbial drivers of disease. The overall goal of the program is to develop novel microbiota-targeted therapies. Dr. Kashyap has published nearly 100 peer reviewed articles including journals like Cell, Cell Host Microbe, Science Translational Medicine, Nature Communications, and Gastroenterology. He was inducted to American Society of Clinical Investigation in 2021. He has previously served on the scientific advisory board of American Gastroenterology Association Gut Microbiome Center, and on the council of American Neurogastroenterology and Motility Society. He now serves on the council and the research committee of AGA, in an editorial role for Gut Microbes and as an ad hoc reviewer on NIH study sections.

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

/in Podcast, Season Three /by Laura

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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 33: From probiotic mechanisms to applications, with Prof. Graciela Lorca PhD

/in Podcast, Season Three /by Laura

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This episode, we discuss how to advance from probiotic mechanisms to human applications, with Prof. Graciela Lorca PhD at the University of Florida in Gainesville, USA. Prof. Lorca talks about her experiences seeking out the mechanisms of action of a probiotic – including which molecules from bacteria may have beneficial effects – and bringing a probiotic through drug trials for use in Type 1 diabetes. They also discuss probiotic responders versus nonresponders and how dietary intake may provide clues about who will respond to an intervention.

Key topics from this episode:

  • Prof. Lorca’s lab is primarily concerned with discovering the mechanisms of action of specific probiotics, including the molecules they produce that can have beneficial effects on a host.
  • Knowing how a probiotic works allows scientists to select strains that are likely to be effective for a certain application.
  • Prof. Lorca’s lab found that L. johnsonii produces extracellular vesicles (EVs) and that a few proteins carried in these EVs may be important markers of where and how they affect the host. She triggered antibodies against these proteins, allowing them to be tracked in the host.
  • EVs are small protrusions from the bacterial membrane, and only some bacteria produce them. Evs have complex cargo, which mostly represents the metabolic state of the cell.
  • Prof. Lorca studied bacteria that appeared to affect autoimmunity in animal models. In humans, administering these bacteria changed immune markers; this intervention is now in a Phase II trial with humans who have Type 1 diabetes. The bacteria may be acting in the small intestine, but they don’t colonize permanently.
  • Extensive data on safety were required to advance the probiotic through to a Phase II trial. Although administering EVs could be an even safer approach, they are difficult to purify from bacteria. Prof. Lorca continues to investigate the bioactive components of these EVs to perhaps administer only those components.
  • Prof. Lorca is also interested in responders versus nonresponders to a probiotic intervention. One of her clinical trials showed that people had either high lactic acid bacteria (LAB) or low LAB at baseline. For those with high levels of LAB, the levels didn’t change much over time. But for those with initially low levels of LAB, the levels increased over time. The latter responded better to treatment. Furthermore, people with high LAB were shown to consume a diet with more long-chain fatty acids, which LAB can utilize. Overall, dietary intake may be a key part of uncovering responders and nonresponders.
  • Over the next ten years in this field, Prof. Lorca believes we will be able to increasingly personalize probiotics according to someone’s genetics and dietary intake. Regulatory aspects are complicated but continue to evolve.

Episode links:

Additional resources:

About Prof. Graciela Lorca PhD:

Dr. Graciela Lorca is currently a Professor in the Department of Microbiology and Cell Science at the University of Florida. She completed her Licentiate in Genetics studies at the National University of Misiones and later received her doctoral degree in Food Technology at the National University of Tucuman in Argentina. She completed her postdoctoral studies at the University of California San Diego in Molecular Microbiology and at the University of Toronto in Structural Biology and Gene Regulation. Since joining the Department of Microbiology and Cell Science at the University of Florida in 2007, Dr. Lorca has focused on the identification of environmental signals that modulate host-microbe interactions. Using multiomic approaches, her laboratory is investigating the bacterial components such as extracellular vesicles that target host pathways involved on those beneficial interactions in vitro and in vivo. Furthermore, Dr. Lorca’s laboratory is currently conducting human trials to evaluate the use of Lactobacillus johnsonii Type 1 Diabetes patients. Dr. Lorca currently teaches a graduate and undergraduate level Probiotics course. She is also in charge of the new concentration on Microbiome in health and disease within the Online Master program at Department of Microbiology and Cell Science.