Small intestinal microbial fiber metabolism dysfunction in celiac disease

Celiac disease (CeD) is an immune-mediated condition driven by dietary gluten resulting in small intestinal mucosal inflammation and injury, along with myriads of symptoms. The only treatment is a lifelong gluten-free diet (GFD) and although most patients improve, the restriction can lead to nutrient deficiencies including fiber. Duodenal microbiota is known to be altered in CeD, but whether and how the microbial fiber metabolism may be affected is unknown. Here we show that CeD patients had impaired microbial fiber metabolism in the small intestine which associated with depletion of the fiber degrading taxa, Prevotella spp, independent of treatment with the GFD. Colonization of germ-free mice with Prevotella spp increased small intestinal short chain fatty acids (SCFA). In gluten-sensitized mice expressing the celiac risk gene, HLA-DQ8, an inulin-supplemented diet facilitated microbial saccharolytic function and SCFA production to accelerate mucosal healing in the small intestine during the GFD. The results support clinical investigations of dietary fiber supplementation and microbial fiber degradation to enhance responses to the GFD in CeD.