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. While duodenal microbiota is altered in CeD, its fiber metabolic capacity is unknown. Here we show that both active and GFD-treated CeD patients had impaired microbial fiber metabolism in the small intestine which associates with depletion of the carbolytic taxa Prevotella spp. 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 carbolytic function, SCFAs production and accelerated mucosal healing in the small intestine during GFD. The results support clinical investigations of dietary fiber supplementation and microbial carbolytic function to enhance responses to GFD in CeD.