Fiber-deficient diet inhibits colitis through regulation of the niche and metabolism of a gut pathobiont Raw sequence reads

Exclusive enteral nutrition (EEN) with fiber-free or fiber-low formula diets is an effective steroid-sparing treatment to induce clinical remission in children with Crohns disease (CD). However, the mechanism underlying the beneficial effects of EEN remains obscure. Using a model of microbiota-dependent colitis with the hallmarks of CD, we found that administration of a fiber-free diet prevented the development of colitis and inhibited intestinal inflammation in colitic animals. Remarkably, fiber-free diet altered the intestinal localization of Mucispirillum schedlaeri, a pathobiont living in the mucus layer, which was required for triggering disease. Mechanistically, the absence of dietary fiber reduced nutrient availability and impaired a unique metabolic pathway of the mucus-dwelling pathobiont in the mucus layer. Thus, appropriate localization of the specific pathobiont in the mucus layer is critical for triggering disease, which is disrupted by fiber exclusion. These results suggest strategies to treat CD by targeting the intestinal niche and metabolism of disease-causing microbes.