Roseburia intestinalis and Its Metabolite Butyrate Inhibit Colitis and Upregulate TLR5 through the SP3 Signaling Pathway

Abstract

The pathogenesis of ulcerative colitis (UC) is unclear, but it is generally believed to be closely related to an imbalance in gut microbiota. <i>Roseburia intestinalis</i> (<i>R. intestinalis</i>) might play a key role in suppressing intestinal inflammation, but the mechanism of its anti-inflammatory effect is unknown. In this study, we investigated the role of <i>R. intestinalis</i> and Toll-like receptor 5 (TLR5) in relieving mouse colitis. We found that <i>R. intestinalis</i> significantly upregulated the transcription of TLR5 in intestinal epithelial cells (IECs) and improved colonic inflammation in a colitis mouse model. The flagellin of <i>R. intestinalis</i> activated the release of anti-inflammatory factors (IL-10, TGF-β) and reduced inflammation in IECs. Furthermore, butyrate, the main metabolic product secreted by <i>R. intestinalis</i>, regulated the expression of TLR5 in IECs. Our data show that butyrate increased the binding of the transcription factor Sp3 (specificity protein 3) to the TLR5 promoter regions, upregulating TLR5 transcription. This work provides new insight into the anti-inflammatory effects of <i>R. intestinalis</i> in colitis and a potential target for UC prevention and treatment.