CNCM I-745 synergizes with the small intestinal microbiota to boost AhR signaling in celiac disease.

Abstract

Celiac disease (CeD) is an immune-mediated condition that leads to small intestinal villous atrophy and is driven by dietary gluten in individuals carrying HLA-DQ2 and DQ8. Microbial factors have been implicated in both the onset of CeD and persistent symptoms (non-responsive CeD) after the gluten-free diet (GFD), through mechanisms including impaired tryptophan metabolism and aryl hydrocarbon receptor (AhR) pathway activation. Although probiotics have been shown to be safe in CeD, there are currently no clinical recommendations for strains that target disease-related mechanisms. We here demonstrate thatactivated the AhR pathway in gluten-sensitized mice expressing HLA-DQ8, improving gluten-immunopathology. Mechanistically,enhanced the CeD patients' microbiota capacity for AhR activation when duodenal indole-producing commensals, such as, were present. Our study provides preclinical evidence thatCNCM I-745 targets a microbial deficiency previously described in CeD through modulation of microbial tryptophan metabolism. The findings encourage clinical testing ofin CeD to prevent or better treat non-responsive cases.