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

Abstract

The commensal bacterium <i>Alistipes shahii</i> 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 <i>A. shahii</i> strain As360 intervention on host inflammatory response and found that <i>A. shahii</i> 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 <i>A. shahii</i> As360 treatment. In addition, <i>A. shahii</i> As360 treatment led to alterations in cytokine release, especially an increase of IL10. It also led to reduced expressions of <i>mtor</i> and <i>Nlrp3</i> and increased expression of mTOR inhibitor <i>Ddit4</i> at the transcriptional level. 16S rRNA amplicon sequencing found that <i>Bacteroides</i>, a producer of short-chain fatty acids (SCFAs), was enriched in the fecal samples of mice with <i>A. shahii</i> treatment. Metabolic analyses found that, following <i>A. shahii</i> 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 <i>A. shahii</i> As360 is a promising strategy to prevent colitis.IMPORTANCEAs one of the core microbes and keystone species in the human gut, <i>Alistipes shahii</i> has the potential to inhibit inflammation and improve inflammatory bowel diseases (IBDs) conditions. In this study, we experimentally demonstrated that oral administration of <i>A. shahii</i> 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 <i>A. shahii</i> and its perspective for better strategies to prevent IBD.