Gut microbiota, dietary fiber, and inflammatory bowel disease - Abstract A large body of epidemiological research suggests an important role for dietary fiber, the collective term for the components of plant-based foods that cannot be catabolized by human digestive enzymes, in promoting health More specifically, consumption of fiber-rich diets is associated with reduced risk of developing numerous chronic inflammatory diseases, including diseases that primarily affect the intestinal tract, such as inflammatory bowel diseases (IBD), as well as the wide array of diseases associated with low-grade intestinal inflammation including metabolic syndrome and cancer. These associations have led to the one-size-fits-all recommendation to eat more fiber prompting increased consumption of foods labeled “high-fiber”, which, in the U.S., includes foods naturally rich in fiber such as whole wheat breads and highly processed foods (HPF) enriched with refined fibers such as inulin. Additionally, consumption of purified fiber supplements, the most common of which is psyllium, has increased. However, the extent to which such increased fiber consumption is beneficial, or even safe, is far from clear. Some interventional studies reported marked benefits while others observed minimal effects and individual case reports suggest the possibility of rare but devastating consequences. Our studies in tractable mouse models demonstrate that enriching diets with fiber can, in a fiber-specific manner, mitigate or exacerbate intestinal inflammation via mechanisms that remain poorly understood. Such ignorance impedes rational development of fiber-enriched foods and fiber supplements as safe and effective health tools. The central goal of this proposal is to help fill this gap in critical knowledge. The current paradigm treats fiber supplements as a monolithic entity or in binary format as insoluble or soluble chemicals with the former providing motility-promoting bulk while the latter is metabolized by microbiota to short-chain fatty acids (SCFA), which have an array of beneficial impacts. Our work challenges that paradigm, which is too rudimentary and fails to capture the breadth of fiber’s impacts on the intestine. Rather, we find that distinct purified fibers have diverse bioactions, many of which are mediated by microbiota but not by SCFA. Furthermore, the mechanisms of action of the mixtures of fibers naturally present in food, and thus more likely to reflect benefits of foods naturally rich in fiber have barely been studied. We propose to fill these foundational knowledge gaps focusing on specific questions germane to rational, safe, and effective deployment of fiber supplements and fiber- enriched foods. We use murine colitis models as a tractable platform of mechanistic discovery but anticipate results that our results will be applicable to other inflammatory diseases and testable in humans.
