Diet is a strong modifier of gut host-microbe interactions that alter host physiology and immunity against pathogenic bacteria. Some dietary components are required to support host defences that maintain gut homeostasis and symbiosis, whereas others can be detrimental, leading to changes in microbial communities and impaired intestinal barrier function and immunity. In this thesis, a mouse model of infectious Citrobacter rodentium was used to challenge the effects of phytochemical and vitamin B12 consumption on intestinal ecology and integrity to promote health. The fiber and phytochemical content in the seed coat of peas (Pisum sativum) has been associated with beneficial health outcomes, including weight and cardiovascular health; however, the indirect effects of peas by host-microbe interactions remain poorly understood. To determine the effect of pea phytochemicals and fiber on host-microbe interactions and intestinal health, the seed coat of two cultivars of peas rich and poor in proanthocyanidins were fed to mice as raw or acid hydrolyzed fractions. In accordance with a previous study, the acid hydrolyzed anthocyanidin fraction reduced weight gain in mice fed a high fat diet. Supplementation of both pea seed coat fractions altered the microbial communities and encouraged pathogen colonization by day three post-infection; however, the proanthocyanidin containing diet had a more robust antimicrobial affect and consistently led to higher pathogen loads as determined by fecal enumeration. Acid hydrolysis processing to both pea fractions reduced the effects on the microbiota and ability of C. rodentium to colonize the gut. In addition, pea phytochemicals increased mucin accumulation in the intestinal lumen, and this may have contributed to the improved ability of C. rodentium to colonize the gut. This study shows how pea phytochemicals directly contributes to microbial ecology and provides insight into how their antimicrobial and mucin accumulating activities affect the gut environment and pathogen colonization resistance. The effect of mucin accumulation in the gastrointestinal lumen in response to phytochemicals has previously been associated with beneficial health outcomes. Since our study shows that increased mucin corresponded with higher levels of C. rodentium colonization, we set out to determine the contributions of mucin to gut ecology and the dietary phytochemicals that stimulate their effects in the gut. Germ-free mice fed the proanthocyanidin-rich containing fraction stimulated mucin accumulation in the feces, indicating that phytochemicals directly impact the mucus layer independently of the microbiota. Supplementing both the red-osier dogwood extract, a hydrolysable tannin, and our non-hydrolysable proanthocyanidin-rich pea fraction led to greater mucin levels in the feces of conventional mice compared to control. The increase in mucin corresponded to an enrichment in Lachnospiraceae and Clostridium leptum species and a reduction in Romboutsia species in the colon. This study provides insight into how dietary phytochemicals impact specific members of the Firmicutes population and shows that a common compound is likely directing the increased fecal mucin phenotype independently of the gut microbiota. Vitamin B12 is a known modulator of the microbial ecosystem. To determine how B12 impacts the gastrointestinal microbiota, we supplemented it in drinking water at 100 times the amount found in diet and challenged mice with C. rodentium. Survival and early colonization models show that mice supplemented B12 were more susceptible to pathogen colonization and virulence. Cecal meta-transcriptomics revealed that the activities of the Firmicutes population was altered by B12 supplementation and this contributed to a more virulent C. rodentium population as confirmed by reduced glucosidase activity and increased virulence genes. In addition, host interleukin-12p40 cytokine levels were higher from B12 supplementation prior to infection and was determined to be dependent on the microbiota. Collectively, this thesis adds to our understanding of diet-microbe-host interactions that impact intestinal integrity as to improve nutritional strategies and therapies to combat infectious disease and improve health.

Drawing on expert opinions from the fields of nutrition, gut microbiology, mammalian physiology, and immunology, Diet-Microbe Interactions for Human Health investigates the evidence for a unified disease mechanism working through the gut and its resident microbiota, and linking many inflammation-related chronic diet associated diseases. State of the art post-genomic studies can highlight the important role played by our resident intestinal microbiota in determining human health and disease. Many chronic human diseases associated with modern lifestyles and diets — including those localized to the intestinal tract like inflammatory bowel disease and celiac disease, and more pervasive systemic conditions such as obesity, diabetes and cardiovascular disease — are characterized by aberrant profiles of gut bacteria or their metabolites. Many of these diseases have an inflammatory basis, often presenting with a chronic low-grade systemic inflammation, hinting at persistent and inappropriate activation of inflammatory pathways. Through the presentation and analysis of recent nutrition studies, this book discusses the possible mechanisms underpinning the disease processes associated with these pathologies, with high fat diets appearing to predispose to disease, and biologically active plant components, mainly fiber and polyphenols, appearing to reduce the risk of chronic disease development. One comprehensive, translational source for all aspects of nutrition and diet's effect on gastrointestinal health and disease Experts in nutrition, diet, microbiology and immunology take readers from the bench research (cellular and biochemical mechanisms of vitamins and nutrients) to new preventive and therapeutic approaches Clear presentations by leading researchers of the cellular mechanisms underlying diet, immune response, and gastrointestinal disease help practicing nutritionists and clinicians (gastroenterologists, endocrinologists) map out new areas for clinical research and structuring clinical recommendations

The Food Forum convened a public workshop on February 22-23, 2012, to explore current and emerging knowledge of the human microbiome, its role in human health, its interaction with the diet, and the translation of new research findings into tools and products that improve the nutritional quality of the food supply. The Human Microbiome, Diet, and Health: Workshop Summary summarizes the presentations and discussions that took place during the workshop. Over the two day workshop, several themes covered included: The microbiome is integral to human physiology, health, and disease. The microbiome is arguably the most intimate connection that humans have with their external environment, mostly through diet. Given the emerging nature of research on the microbiome, some important methodology issues might still have to be resolved with respect to undersampling and a lack of causal and mechanistic studies. Dietary interventions intended to have an impact on host biology via their impact on the microbiome are being developed, and the market for these products is seeing tremendous success. However, the current regulatory framework poses challenges to industry interest and investment.

“In Missing Microbes, Martin Blaser sounds [an] alarm. He patiently and thoroughly builds a compelling case that the threat of antibiotic overuse goes far beyond resistant infections.”—Nature Renowned microbiologist Dr. Martin J. Blaser invites us into the wilds of the human microbiome, where for hundreds of thousands of years bacterial and human cells have existed in a peaceful symbiosis that is responsible for the equilibrium and health of our bodies. Now this invisible Eden is under assault from our overreliance on medical advances including antibiotics and caesarian sections, threatening the extinction of our irreplaceable microbes and leading to severe health consequences. Taking us into the lab to recount his groundbreaking studies, Blaser not only provides elegant support for his theory, he guides us to what we can do to avoid even more catastrophic health problems in the future. “Missing Microbes is science writing at its very best—crisply argued and beautifully written, with stunning insights about the human microbiome and workable solutions to an urgent global crisis.”—David M. Oshinsky, author of the Pulitzer Prize-winning Polio: An American Story