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

Exclusive enteral nutrition (EEN) with fiber-free diets is an effective steroid-sparing treatment to induce clin-ical remission in children with Crohn's disease (CD). However, the mechanism underlying the beneficial ef-fects of EEN remains obscure. Using a model of microbiota-dependent colitis with the hallmarks of CD, we find that the administration of a fiber-free diet prevents the development of colitis and inhibits intestinal inflammation in colitic animals. Remarkably, fiber-free diet alters the intestinal localization of Mucispirillum schaedleri, a mucus-dwelling pathobiont, which is required for triggering disease. Mechanistically, the absence of dietary fiber reduces nutrient availability and impairs the dissimilatory nitrate reduction to ammonia (DNRA) metabolic pathway of Mucispirillum, leading to its exclusion from the mucus layer and dis-ease remission. Thus, appropriate localization of the specific pathobiont in the mucus layer is critical for dis-ease development, which is disrupted by fiber exclusion. These results suggest strategies to treat CD by tar-geting the intestinal niche and metabolism of disease-causing microbes.