alleviated colitis by downregulating the TNF signaling pathway mediated by cIAP1/2 in mice.

The gut microbiota and its associated micro-ecosystem are closely related to the onset and development of ulcerative colitis (UC). It is known that () helps rebuild gut eubiosis from diabetes dysbiosis; however, its effects on UC remain unknown. This study aims to investigate the therapeutic effects and mechanisms of on UC. In this study, was encapsulated with thiolated hyaluronic acid (HA-SH) to form a hydrogel, termed as CG-HA-SH. The adhesion and distribution of CG-HA-SH in the intestine were evaluated, along with its therapeutic effects on UC mice, including its impact on the gut microbiota. Additionally, changes in short-chain fatty acids (SCFAs) in the intestines of UC mice were analyzed, and RNA sequencing (RNA-Seq) was employed to investigate the mechanisms by which alleviated inflammation. HA-SH enhanced the resistance of in gastric and intestinal fluids, providing approximately 12 hours of adhesion at colitis inflammation sites. reduced the levels of pro-inflammatory factors such as IL-1β (by 97.31%) and TNF-α (by 90.10%) while increasing anti-inflammatory IL-10 levels (by 197.59%) in the colon. It also increased the abundance of , , and butyrate and enhanced intestinal tight junctions (OCC, by 318.93%) and the mucus barrier (MUC2, by 515.93%). The mRNA levels of cIAP1/2 decreased by 4.33-fold, and their protein expression levels were reduced by 36.97% correspondingly. The enrichment of the TNF pathway was the most significant. Therefore, exhibited remarkable efficacy in alleviating inflammation and reshaping dysbiotic gut microbiota by downregulating the cIAP1/2-mediated TNF signaling pathway and NF-κB signaling pathway. cIAP1 and cIAP2 might serve as effective therapeutic targets.