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Episode 27: Investigating the benefits of live dietary 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.

Investigating the benefits of live dietary microbes, with Prof. Colin Hill PhD and Prof. Dan Tancredi PhD

Episode summary:

In this episode, the ISAPP podcast hosts themselves are the experts: Prof. Colin Hill PhD from APC Microbiome Ireland / University College Cork and Prof. Dan Tancredi PhD from University of California – Davis talk about their recent work investigating the health benefits from consuming higher quantities of live dietary microbes – and not just microbes that meet the probiotic criteria.

Key topics from this episode:

  • Profs. Hill and Tancredi were involved with others in a recent series investigations & 3 published papers on whether there should be a recommended daily intake of live microbes.
  • Prof. Hill started by writing a blog, prompted by the finding that meta-analyses on probiotics tended to show some general benefits for health. Would this apply to any safe, live microbes – even those that do not meet the probiotic criteria?
  • Various hypotheses (hygiene hypothesis, old friends hypothesis, missing microbes hypothesis) posit that a lack of microbes is associated with poorer health.
  • Clean water and clean food have reduced the burden of infectious disease. But at the same time, across populations there has been an increase in chronic diseases. Could a lack of live dietary microbes be contributing to this increase in chronic disease, because the immune system lacks adequate inputs? Or in other words, could there be a general health benefit for healthy people in consuming high quantities of live microbes?
  • To address the hypothesis scientifically: they investigated the health status of people who eat large vs. small numbers of safe live microbes in their diets. Starting with NHANES data in the US, the researchers classified foods into categories of high / medium / low numbers of live microbes.
  • Note that not all fermented foods contain live microbes, but some contain high numbers of live microbes. A possible confounding factor in the analysis was that high microbe foods tend to be healthier foods.
  • The researchers published a series of 3 papers. The 3rd paper showed an association between intake of live microbes and various (positive) measurements of health. Consistent, modest improvements were seen across a range of health outcomes.
  • This is an association, but statistically the team did use regression analysis to statistically adjust for effects on health that could be due to other factors besides the live microbial intake.
  • The take-home is not to eat unsafe or rotten food, but rather to eat more high-microbe or fermented foods, and in general eat a healthy diet.

Episode links:

Additional Resources:

Live Dietary Microbes: A role in human health. ISAPP infographic.

About Prof. Colin Hill PhD:
Colin Hill has a Ph.D in molecular microbiology and is a Professor in the School of Microbiology at University College Cork, Ireland. He is also a founding Principal Investigator in APC Microbiome Ireland, a large research centre devoted to the study of the role of the gut microbiota in health and disease. His main interests lie in the role of the microbiome in human and animal health. He is particularly interested in the effects of probiotics, bacteriocins, and bacteriophage. In 2005 Prof. Hill was awarded a D.Sc by the National University of Ireland in recognition of his contributions to research. In 2009 he was elected to the Royal Irish Academy and in 2010 he received the Metchnikoff Prize in Microbiology and was elected to the American Academy of Microbiology. He has published more than 600 papers and holds 25 patents. More than 80 PhD students have been trained in his laboratory. He was president of ISAPP from 2012-2015.

About Prof. Dan Tancredi PhD:
Daniel J. Tancredi, PhD, is Professor in Residence of Pediatrics in the University of California, Davis School of Medicine. He has over 25 years of experience and over 300 peer-reviewed publications as a statistician collaborating on a variety of health-related research. A frequent collaborator on probiotic and prebiotic research, he has attended all but one ISAPP annual meeting since 2009 as an invited expert. In 2020, he joined the ISAPP Board of Directors. Colin Hill and Daniel co-host the ISAPP Podcast Series “Science, Microbes, and Health”. On research teams, he develops and helps implement effective study designs and statistical analysis plans, especially in settings with clusters of longitudinal or otherwise correlated measurements, including cluster-randomized trials, surveys that use complex probability sampling techniques, and epidemiological research. He teaches statistics and critical appraisal of evidence to resident physicians; graduate students in biostatistics, epidemiology, and nursing; and professional scientists. Dan grew up in the American Midwest, in Kansas City, Missouri, and holds a bachelor’s degree in behavioral science from the University of Chicago and masters and doctoral degrees in mathematics from the University of Illinois at Chicago. He lives in the small Northern California city of Davis, with his wife Laurel Beckett (UC Davis Distinguished Professor Emerita), their Samoyed dogs Simka and Milka, and near their two grandkids.

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.

Using probiotics to support digestive health for dogs

By Kelly S. Swanson, PhD, The Kraft Heinz Company Endowed Professor in Human Nutrition, University of Illinois at Urbana-Champaign, USA

Because dogs are considered to be members of the family by most pet owners today, their health and well-being is a top priority. As with humans, nutritional products supporting gastrointestinal health are some of the most popular. Many pets are healthy, but loose stools, constipation, and various gastrointestinal disorders and diseases such as inflammatory bowel disease and irritable bowel syndrome are common. In fact, within the pet food conversation, digestive health improvements have been the most discussed health benefits among social media discussion posts over the past 2 years (see here). Given the high interest in digestive health, it is not surprising that the canine microbiome has been of great interest over the past decade, with many recent reviews reporting on the overall composition of the gastrointestinal microbiota and how it is impacted by diet (Barko et al., 2018; Alessandri et al., 2020; Wernimont et al., 2020). Gastrointestinal microbiome changes contributing to or resulting from digestive diseases have also been documented in dogs (Redfern et al., 2017; Ziese and Suchodolski, 2021). Animals under high levels of stress or undergoing antibiotic therapy are also known to have poor stool quality and an altered gut microbiota (i.e., dysbiosis) (Pilla et al., 2020).

Dietary fibers and prebiotics are commonly used in complete and balanced diets to improve or maintain stool quality, provide laxation, and positively manipulate the microbiota of healthy animals. The use of probiotics is also popular in dogs, but the route of administration, efficacy, and reason for use is usually different than that of fiber and prebiotics. Probiotics are usually provided in the form of supplements (e.g., powders, capsules, pastes) and are most commonly used to treat animals with gastrointestinal disease rather than support the healthy condition. Live microbes are added to many dry extruded foods as ‘probiotics’, but in many cases, maintaining viability and evidence for a health benefit for dogs is lacking for these products. Such microbes would not meet the minimum criteria to be called a ‘probiotic.’ Viability is a challenge because most HACCP plans for producing complete and balanced pet foods include a kill step that inactivates all microorganisms. Therefore, inclusion must be applied post-extrusion on the outside of the kibble. Even if applied in this way, low numbers of viable organisms are common (Weese and Arroyo, 2003). Post-production inclusion is not possible for other diet formats (e.g., cans, pouches, trays). Although spore-forming bacteria that may survive the extrusion process have been of interest lately, evidence of efficacy is lacking thus far.

Picture of Simka (a Samoyed) courtesy of ISAPP board member Dr. Daniel Tancredi

Even though health benefits coming from the inclusion of live microorganisms in dog foods is not supported by the peer-reviewed literature, such evidence exists for many probiotic supplements. The clinical effects of probiotics in the prevention or treatment of gastrointestinal diseases in dogs have been reviewed recently (Schmitz and Suchodolski, 2016; Suchodolski and Jergens, 2016; Jensen and Bjornvad, 2018; Schmitz, 2021). Although some similarities exist, recent research has shown that distinct dysbiosis networks exist in dogs compared to humans (Vazquez-Baeza et al., 2016), justifying unique prevention and/or treatment strategies for dogs.

One population of dogs shown to benefit from probiotics has been those with acute idiopathic diarrhea and gastroenteritis, with a shorter time to resolution and reduced percentage of dogs requiring antibiotic administration being reported (Kelley et al., 2009; Herstad et al., 2010; Nixon et al., 2019). Probiotic administration has also been shown to benefit dogs undergoing antibiotic therapy and those engaged in endurance exercise – two conditions that alter the gastrointestinal microbiota and often lead to loose stools. In those studies, consumption of a probiotic helped to minimize gastrointestinal microbiome shifts and reduced the incidence and/or shortened the length of diarrhea (Gagne et al., 2013; Fenimore et al., 2017). Dogs diagnosed with inflammatory bowel disease have also been shown to benefit from probiotic consumption (Rossi et al., 2014; White et al., 2017). In these chronic conditions, drug therapy is almost always required, but probiotics have been shown to help normalize intestinal dysbiosis, increase tight junction protein expression, and reduce clinical and histological scores.

So what is the bottom line? Well, for dogs with a sensitive stomach and/or digestive health issues, probiotics may certainly help. Rather than relying on live microbes present in the dog’s food or adding a couple spoonfuls of yogurt to the food bowl each day, it is recommended that owners work with their veterinarian to identify a probiotic that has the best chance for success. The probiotic selected should provide an effective dose, be designed for dogs, target the specific condition in mind, and be backed by science. As summarized here, it is important to remember that all probiotics are different so the specific microorganism(s), supplement form, storage conditions, and dosage are all important details to consider.

 

Kelly Swanson joined the ISAPP board of directors in June, 2020, providing valuable expertise in animal gut health and overall health. Swanson also chaired the 2019 ISAPP-led international consensus panel on the definition of synbiotics.

ISAPP board member Prof. Dan Tancredi kindly provided pictures of Simka, pet Samoyed, for the post.