The human gut microbiota is a complex consortium of microbes that includes bacteria, viruses, archaea, and fungi. There are enormous numbers of bacteria in the gut with a collective genome estimated at 150-fold greater than the size of our own genome. Thus, the gut microbiota can produce small molecules, some determined by dietary substrates that are unique and cannot be produced by mammalian cells. Growing evidence suggests that these small molecules may play a role in the pathogenesis of certain diseases, a number of which are associated with "dysbiosis" – alteration in the composition of the microbiota.
Dr. Gary D. Wu
One strategy to maintain health and/or treat disease might involve altering the dysbiotic gut microbiota through dietary intervention. Although the interaction between diet and the gut microbiota is complex, investigators have shown consistently that decreases in gut microbiome "richness" (numbers of various bacteria and their genes) is associated with both disease states and the consumption of a Westernized diet. Using this knowledge, investigators are very interested in determining whether or not dietary interventions, such as defined formula and/or elemental diets, successfully treat Crohn’s disease via a gut microbiome–dependent mechanism. The ultimate goal of such research is to develop a "healthier" diet for patients suffering from inflammatory bowel disease.
Diet not only alters the composition of the gut microbiota but it also serves as a substrate by which it can produce a large number of small molecules that, after first pass metabolism through the liver, can circulate systemically and have important effects on host physiology. For example, the conversion of dietary fats from choline into trimethyl amine (TMA) by the microbiota and its subsequent oxidation by the liver, leads to the production of TMAO, a small molecule that accelerates coronary vascular disease in mice and is a biomarker for patients at risk for atherosclerotic heart disease in humans. The enzyme in bacteria that leads to the production of TMA from choline has been described, thus opening up opportunities for the development of gut microbiota–based biomarkers that could be used to stratify the risk of coronary vascular disease in humans. Conceptually, strategies targeting TMA-producing bacteria and/or novel dietary modifications might also be developed to reduce the risk of heart disease.
Similar strategies could be used to develop gut microbiota–based therapies targeting immune-mediated disease, such as IBD and asthma, with a focus on the consumption of fermentable carbohydrates, the production of short-chain fatty acids, the activation of G-protein coupled receptors, and the restoration of immune tolerance through T regulatory cells. Ultimately, there may be significant opportunities to enhance current dietary interventions that target the gut microbiota, such as prebiotics, probiotics, and synbiotics, to develop more potent and effective interventions by applying the vast amount of new knowledge gained over the past decade from the study of the interaction between diet and the gut microbiome.
Dr. Wu is the Ferdinand G. Weisbrod Professor of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.
