Gut commensal Alistipes shahii improves experimental colitis in mice with reduced intestinal epithelial damage and cytokine secretion

Abstract

ABSTRACT The commensal bacterium Alistipes shahii is a core microbe of the human gut microbiome and its abundance is negatively correlated with inflammatory bowel diseases (IBDs). However, its fundamental role in regulating inflammatory response remains unknown. Using a dextran sulfate sodium (DSS)-induced colitis mouse model, we examined the effect of A. shahii strain As360 intervention on host inflammatory response and found that A. shahii As360 alleviated disease activity index, colon shortening, and colonic histopathological lesion. The levels of tight junction proteins (mainly ZO1 and claudin-1) were decreased in DSS-induced colitis mice, whereas the levels of these proteins were elevated in colitis mice with A. shahii As360 treatment. In addition, A. shahii As360 treatment led to alterations in cytokine release, especially an increase of IL10. It also led to reduced expressions of mtor and Nlrp3 and increased expression of mTOR inhibitor Ddit4 at the transcriptional level. 16S rRNA amplicon sequencing found that Bacteroides, a producer of short-chain fatty acids (SCFAs), was enriched in the fecal samples of mice with A. shahii treatment. Metabolic analyses found that, following A. shahii As360 treatment, the SCFAs in the fecal content was increased whereas lactic acid was decreased in the cecal content. These findings suggest that supplementation with A. shahii As360 is a promising strategy to prevent colitis.IMPORTANCEAs one of the core microbes and keystone species in the human gut, Alistipes shahii has the potential to inhibit inflammation and improve inflammatory bowel diseases (IBDs) conditions. In this study, we experimentally demonstrated that oral administration of A. shahii As360 alleviated symptoms of colitis, altered the release of cellular inflammatory factors, reduced the intestinal epithelial barrier damage, and changed gut microbiota and fecal metabolites. These findings provide a deeper understanding of the beneficial effects of A. shahii and its perspective for better strategies to prevent IBD.

Keywords

• Alistipes shahii
• inflammatory bowel diseases
• short-chain fatty acids
• inflammatory cytokines
• mTOR