Dietary Protein Source Mediates Colitis Pathogenesis Through Bacterial Modulation of Bile Acids

Background & Aims Evidence-based dietary recommendations for individuals with inflammatory bowel diseases are limited. Red meat consumption is associated with increased inflammatory bowel disease incidence and relapse in patients, suggesting that switching to a plant-based diet may limit gut inflammation. However, the components and mechanisms underlying the differential effects of these diets remain poorly understood. This study investigated the differential impact of dietary protein source on experimental colitis and related mechanisms. Methods Isocaloric synthetic diets containing protein isolates from beef, egg whites, casein, soy, or pea were tested in acute (dextran sodium sulfate–induced) and chronic ( Il10- deficient) murine colitis models. Gut resident microbes were quantified with 16S-sequencing, and their role was evaluated by antibiotic depletion, germ-free, selectively colonized gnotobiotic, and fecal microbiota transplant mouse studies. Results Mice fed a beef protein diet exhibited the most severe colitis, whereas mice fed pea protein developed mild inflammation. The colitis-promoting effects of beef protein were microbially mediated. In the absence of colitis, beef protein feeding reduced the abundance of Lactobacillus johnsonii and Turicibacter sanguinis and expanded Akkermansia muciniphila , which localized to the mucus in association with decreased mucus thickness and quality. Beef protein–fed mice had elevated primary and conjugated fecal bile acids, and taurocholic acid administration to pea protein–fed mice worsened colitis. Dietary psyllium protected against beef protein–mediated inflammation, restored bile acid–modulating commensals, and normalized bile acid ratios. Conclusions These data suggest that the protein component of red meat may be responsible, in part, for the colitis-promoting effects of this food source and provide insight into dietary factors that may influence inflammatory bowel disease severity.