New Advances: Diet and Microbiome

State of the Science on Microbiota, Diet & Dietary Patterns

Gary D. Wu, PhD, MD, Ferdinand G. Weisbrod Professor in Gastroenterology, Co-Director PennCHOP Microbiome Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

The human gut contains a vast number of microorganisms known collectively as the “gut microbiota”. Despite its importance in maintaining the health of the host, growing evidence suggests the gut microbiota may also be an important factor in the pathogenesis of various diseases, a number of which have shown a rapid increase in incidence over the past few decades. In some of these diseases, such as inflammatory bowel disease (IBD), the microbiota is “dysbiotic” with an altered community structure and decrease in diversity. If the dysbiotic microbiota plays a role in disease pathogenesis, interventions that modify its composition might be a strategy to treat certain disease processes. The composition of the microbiota can be influenced by many factors including age, genetics, host environment, and diet. Diet has an impact upon both the composition and function of the microbiota in part through small molecule production that may influence the development of both immune-mediated and metabolic diseases. There are a number of ways by which this interaction can be exploited to promote human health including the use of gut microbiome composition to develop personalized diets for the treatment of metabolic syndrome, protect mucus barrier function in the intestinal tract, and as a modality to treat immunologically based diseases such as IBD. In total, there is growing evidence supporting the notion that the dietary manipulation of the gut microbiota and its metabolome can be used as a modality to both maintain health and treat disease. In order to accomplish this goal, there is a need for human intervention studies to demonstrate cause-and-effect relationships.

A Gut Feeling about the Brain: Diet, Microbiome & Behavior

John F. Cryan, PhD, APC Microbiome Institute, University College Cork, Cork, Ireland

The brain-gut-microbiota axis is emerging as a research area of increasing interest for those investigating the biological and physiological basis of brain development and behaviour across the lifespan. A growing body of evidence supports the role of this microbiota in influencing host appetite and food intake. The routes of communication between the gut and brain include the vagus nerve, the immune system, tryptophan metabolism, via the enteric nervous system or by way of microbial metabolites such as short chain fatty acids. These mechanisms also impinge on neuroendocrine function at multiple levels. Studies in animal models have been key in delineating that neurodevelopment and the programming of an appropriate stress response is dependent on the microbiota. Developmentally, a variety of factors can impact the microbiota in early life including mode of birth delivery, antibiotic exposure, mode of nutritional provision, infection, stress as well as host genetics.  At the other extreme of life, individuals who age with considerable ill health tend to show narrowing in microbial diversity. Stress can significantly impact the microbiota-gut-brain axis at all stages across the lifespan. Moreover, fundamental brain processes from adult hippocampal neurogenesis to myelination to microglia activation have been shown to be regulated by the microbiome. A growing body of evidence indicates that there is a crucial role for the microbiota in regulating different aspects of eating-related behaviour, as well as behavioural comorbidities of eating and metabolic disorders. Finally, studies examining the translation of these effects from animals to humans are currently ongoing. Further studies will focus on understanding the mechanisms underlying such brain effects and developing nutritional and microbial-based intervention strategies.

Shaping the Gut Microbiome During Infancy

Anita Kozyrskyj, PhD, Professor, Pediatrics, University of Alberta, Edmonton, Alberta, Canada

Established during infancy, our complex gut microbial community is shaped by medical interventions and societal preferences, such as cesarean section, formula-feeding and antibiotic use. The SyMBIOTA (Synergy in Microbiota) research program aims to quantify age-specific and longitudinal changes in gut microbial composition during infancy following the most common birth and postnatal events affecting infant gut microbial composition. Gut microbiota profiles of full-term infants in the general population Canadian Healthy Infant Longitudinal Development birth cohort were obtained using 16S high-throughput gene sequencing. At 3 months of age, depletion of Bacteroidetes and enrichment of Firmicutes (genera Clostridium and Enterococcus) was observed in the infant gut following cesarean delivery and maternal antibiotic prophylaxis during vaginal birth. Fewer changes were detected at 1 year of age, largely among infants who were not exclusively breastfed for at least 3 months. From 3 months to 1 year of age, well-known patterns of microbial phyla succession in later infancy (declining Proteobacteria; increasing Firmicutes and Bacteroidetes) following vaginal birth, breastfeeding and no antibiotic exposure. Genus Lactobacillus, Roseburia and Faecalibacterium species appeared in the top 10 increases to microbial abundance in these infants. Deviations from this pattern were evident among infants with birth and postnatal interventions; notably, the largest number of microbial species with unchanged abundance was seen in gut microbiota following early cessation of breastfeeding in infants. Gut microbiota of infants born vaginally and exclusively formula-fed became less enriched with family Veillonellaceae and Clostridiaceae, showed unchanging levels of Ruminococcaceae and exhibited a greater decline in the Rikenellaceae/ Bacteroideceae ratio compared to their breastfed, vaginally-delivered counterparts. These changes were also evident in cesarean-delivered infants to a lesser extent. The clinical relevance of these trajectories of microbial change is that they culminate in taxon-specific abundances in the gut microbiota of later infancy, which we and others have observed to be associated with food sensitization and overweight.

Workshop on Best Practices in Studies of Diet and the Intestinal Microbiome

Cindy D. Davis, PhD, National Institutes of Health, Christopher J. Lynch, Robert W. Karp and David M. Klurfeld

Many studies of the intestinal microbiome, whether in vitro, in animal models, or in humans report only minimal information about dietary composition despite substantial evidence that diet modulates microbial composition. ILSI North America and USDA sponsored a two-day workshop that was organized by NIH and USDA. This workshop brought together 16 scientific experts to discuss the role of diet in modifying the human gastrointestinal microbiome. The purpose of the workshop was to improve rigor and reproducibility in research on the gastrointestinal microbiome, identify important dietary information that should be reported, and parameters to consider when designing studies on diet and the intestinal microbiome. For all types of studies, strengths and weaknesses of various designs were emphasized and for human studies, comparisons between controlled feeding and observational designs were discussed.  The participants concluded that there are few clearly established best practices for the design of studies on the intestinal microbiome in which diet is a main variable. Moreover, in the absence of clearly superior dietary approaches for specific research questions, the main recommendation is to present dietary information in as much detail as possible so that other researchers can reproduce the work. This emerging field needs to move from associations to causality which will be catalyzed by knowing in as much detail as possible what is ingested, how it is metabolized, and the health consequences derived from these processes.

DeAnn Liska, PhD

DeAnn Liska is the Senior Director of Nutrition Science & Biostatistics at Biofortis - Mérieux NutriSciences, where she leads the team responsible for scientific consultation, design, and interpretation of clinical trials and literature assessments. She has more than 20 years’ experience in the nutrition industry with past leadership roles at Kellogg’s, Ocean Spray, and Metagenics. Dr. Liska holds a PhD in biochemistry (University of Wisconsin) and was an Assistant Research Professor in biochemistry at the University of Washington prior to joining industry. She is a member ILSI North America’s Food, Nutrition & Safety Program (FNSP) Leadership Program, and is on the scientific advisory panels for the Council for Responsible Nutrition and Cornell Division of Nutritional Sciences. Dr. Liska has authored over 50 peer-reviewed publications and is co-inventor on 12 patents.

Chantal Matar PhD, RD                                                         

Dr. Chantal Matar is a professor at the School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa. She obtained her PhD in Food Sciences and Technology from Laval University and completed a Dietetic Internship at Ottawa Hospital. Dr. Matar’s expertise is focused on in vivo assessing of functional foods, probiotics and microbiome in chemoprevention of cancer by controlling cancer stem cells and microRNAs. She is an established investigator with proven track record of supervising highly qualified personnel. Dr. Matar has authored more than 110 communications, including 50 referred papers, book chapters, and patent applications. She was successful in acquiring research funding from different research agencies. In 2014, Dr. Matar received the Best Research Award from Trade and Industry Ministry in Japan and in 2008, an International Union for Cancer Control research fellowship for visiting scientist at WHO.

Gary Wu, PhD, MD

Dr. Wu is the Ferdinand G. Weisbrod Professor in Gastroenterology at the Perelman School of Medicine at the University of Pennsylvania where he is the Associate Chief for Research in the Division of Gastroenterology, the Associate Director of the Center for Molecular Studies in Digestive and Liver Disease, and the Co-Director of the PennCHOP Microbiome Program. He was the inaugural Director and Chair of the Scientific Advisory Board for the American Gastroenterological Association's Center for Gut Microbiome Research and Education and is currently a member of the Governing Board as the Basic Research Councillor. Dr. Wu is an elected member of both the American Society for Clinical Investigation and the Association of American Physicians. Research programs in the Wu laboratory focus on the mutualistic interactions between the gut microbiota and its host with a particular emphasis on metabolism including nitrogen balance, intestinal oxygen regulation, and epithelial intermediary metabolism. Of particular interest is the effect of diet on the gut microbiome and its relationship to therapeutic responses associated with the use of defined formula diets in the treatment of Crohn’s disease. Insights gained from these projects will hopefully lead to the development of better diets for patients with IBD.

As a former member of the NIDDK-C committee and its Chairman in 2007, Dr. Wu is cognizant of the need to foster the careers of young investigators including those in the field of Gastroenterology. Dr. Wu has been the Associate Director of The University of Pennsylvania Training Program in Gastrointestinal Sciences (T32 DK0706) since 1997, member of the GI Fellowship Committee at Penn, and a member of the Scholarly Oversight Committee at the Children’s Hospital of Philadelphia. In this capacity, he has been actively involved in the career development of many GI fellows in the physician-scientist track at Penn. In addition to over two dozen graduate students, post-docs, medical students, and residents that he has mentored over the years, Dr. Wu has specifically mentored nine GI fellows since joining the faculty at the University of Pennsylvania. He is proud of the fact that nearly all of these individuals are full time faculty members at academic medical centers.

John F. Cryan, PhD

John F. Cryan is Professor & Chair of the Department of Anatomy & Neuroscience at the University College Cork, Ireland and is also a Principal Investigator at the APC Microbiome Institute. Prof. Cryan's current research is focused on understanding the interaction between brain, gut & microbiome and how it applies to stress, psychiatric and immune-related disorders at key time-windows across the lifespan. Prof. Cryan has published over 400 articles and is co-author of the forthcoming “The Psychobiotic Revolution: Mood, Food, and the New Science of the Gut-Brain Connection” from National Geographic Press. He has received numerous awards including UCC Researcher of the Year in 2012; the University of Utrecht Award for Excellence in Pharmaceutical Research in 2013 and being named on the Thomson Reuters Highly Cited Researcher list in 2014. He was elected a Member of the Royal Irish Academy in 2017. In that year he also received a Research Mentor Award from the American Gastroenterology Association and the Tom Connor Distinguished Scientist Award from Neuroscience Ireland. He was a TEDMED speaker in 2014 and is currently President of the European Behavioural Pharmacology Society.

Anita Kozyrskyj, PhD

Dr. Anita Kozyrskyj, Professor of Pediatrics at the University of Alberta, has expertise in epidemiological research using population-based birth cohort studies, including the CHILD (Canadian Healthy Infant Longitudinal Development) birth cohort. Her current research focuses on early-life programming of childhood atopic disease and overweight by the infant gut microbiome, as influenced by birth method, infant diet and antibiotic use during pregnancy, birth and infancy. Dr. Kozyrskyj has MS and PhD degrees in community health sciences from the University of Manitoba.

Cindy D. Davis, PhD

Cindy Davis is the Director of Grants and Extramural Activities in the Office of Dietary Supplements (ODS). In this position, she actively engages and encourages partnerships with other NIH Institutes and Centers to facilitate funding of grants that are of high relevance to ODS mission and goals. Dr. Davis is also actively involved in a number of government working groups on the microbiome. Before coming to ODS, she was a Program Director in the Nutritional Sciences Research Group at the National Cancer Institute. Cindy received her bachelor’s degree with honors in nutritional sciences from Cornell University in Ithaca, New York and her doctorate degree in nutrition with a minor in human cancer biology from the University of Wisconsin- Madison. Dr. Davis completed her postdoctoral training at the Laboratory of Experimental Carcinogenesis at the National Cancer Institute.  She then joined the Grand Forks Human Nutrition Research Center, USDA, as a research nutritionist.  In 2000, Dr. Davis received a Presidential Early Career Award for Scientists and Engineers and was named the USDA Early Career Scientist.  She has published more than 125 peer-reviewed journal articles and eleven invited book chapters. She is a supplement editor for Journal of Nutrition, assistant editor for Nutrients, assistant editor for Nutrition Reviews and a member of the editorial board for Advances in Nutrition.