Butyrate mediates anti-inflammatory effects ofFaecalibacterium prausnitziiin intestinal epithelial cells throughDact3

The commensal bacteriumFaecalibacterium prausnitziiplays a key role in inflammatory bowel disease (IBD) pathogenesis and serves as a general health biomarker in humans. However, the host molecular mechanisms that underlie its anti-inflammatory effects remain unknown. In this study we performed a transcriptomic approach on human intestinal epithelial cells (HT-29) stimulated with TNF-alpha and exposed toF. prausnitziiculture supernatant (SN) in order to determine the impact of this commensal bacterium on intestinal epithelial cells. Moreover, modulation of the most upregulated gene afterF. prausnitziiSN contact was validated bothin vitroandin vivo. Our results showed thatF. prausnitziiSN upregulates the expression ofDact3, a gene linked to the Wnt/JNK pathway. Interestingly, when we silencedDact3expression, the effect ofF. prausnitziiSN was lost. Butyrate was identified as theF. prausnitziieffector responsible forDact3modulation.Dact3upregulation was also validatedin vivoin both healthy and inflamed mice treated with eitherF. prausnitziiSN or the live bacteria, respectively. Finally, we demonstrated by colon transcriptomics that gut microbiota directly influencesDact3expression. This study provides new clues about the host molecular mechanisms involved in the anti-inflammatory effects of the beneficial commensal bacteriumF. prausnitzii.