biostudies-literatureUnknown14(1)Qi-Xiang MThis study was funded by grants from the the Clinical Research Cultivating Program of Shanghai Hospital Development CenterToll-like receptor 4 (TLR4) has been identified as a potentially promising therapeutic target in acute pancreatitis (AP). However, the role of intestinal TLR4 in AP and AP-associated gut injury remains unclear. This study aimed to explore the relationship between intestinal TLR4 and gut microbiota during AP. A mouse AP model was establish by intraperitoneal injection of L-arginine. Pancreatic injury and intestinal barrier function were evaluated in wild-type and intestinal epithelial TLR4 knockout (TLR4ΔIEC) mice. Gut microbiota was analyzed by 16S rRNA sequencing. Quadruple antibiotics were applied to induce microbiota-depleted mice. Differentially expressed genes in gut were detected by RNA sequencing. <i>L. reuteri</i> treatment was carried out in <i>vivo</i> and <i>vitro</i> study. ComGut microbes2112882https://www.ebi.ac.uk/biostudies/studies/S-EPMC9397436biostudies-literatureIntestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency.PMC9397436Nuo-Ming YChun-Lan HBin-Qiang XRui-Long WZe-Hua HYang FQi-Xiang MJun-Jie FYue ZfalseIntestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency.Toll-like receptor 4 (TLR4) has been identified as a potentially promising therapeutic target in acute pancreatitis (AP). However, the role of intestinal TLR4 in AP and AP-associated gut injury remains unclear. This study aimed to explore the relationship between intestinal TLR4 and gut microbiota during AP. A mouse AP model was establish by intraperitoneal injection of L-arginine. Pancreatic injury and intestinal barrier function were evaluated in wild-type and intestinal epithelial TLR4 knockout (TLR4ΔIEC) mice. Gut microbiota was analyzed by 16S rRNA sequencing. Quadruple antibiotics were applied to induce microbiota-depleted mice. Differentially expressed genes in gut were detected by RNA sequencing. <i>L. reuteri</i> treatment was carried out in <i>vivo</i> and <i>vitro</i> study. Com2022-01-01T00:00:00Z2022 Jan-Dec2025-08-31T03:17:33.443Z2025-04-06T07:50:21.892ZS-EPMC93974363598260410.1080/19490976.2022.2112882