Jiang Mingshan, Jia Yongbin, Ma Chunxiang, Zeng Zhen, Wu Yushan, Gan Huatian, Zhang Hu
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China.
Inflamm Bowel Dis. 2025 Aug 1;31(8):2217-2230. doi: 10.1093/ibd/izaf057.
Inflammatory bowel disease is a long-standing inflammatory disorder that influences the intestinal tract. The intent of this research is to explore whether the relative abundance of Akkermansia muciniphila is related to the IL6/STAT3 pathway and the fundamental molecular mechanisms of A. muciniphila on a trinitrobenzene sulfonic acid (TNBS)-induced enteritis mouse model, including the expression of inflammatory cytokines and proteins in the IL6/STAT3 signaling pathway.
The association between the A. muciniphila and IL6/STAT3 was investigated by using mucosal biopsies and fecal samples. TNBS-induced colitis mouse models were performed to elucidate the underlying mechanisms. The alteration of intestinal microbiota was organized by 16s rRNA sequencing.
In Crohn's disease patients, the level of STAT3 and IL-6 presented a negative relationship with A. muciniphila. The expression of IL-6, p-STAT3, and STAT3 was downregulated in A.m+TNBS group, indicating A. muciniphila may inhibit the IL6/STAT3 pathway in TNBS-induced enteritis in vivo. To investigate the potential defensive role of A. muciniphila supplementation in vivo with TNBS-induced enteritis, 16S rRNA sequencing was performed to analyze changes in the intestinal microbiota composition. The results revealed a marked increase in microbial diversity and abundance within the A. muciniphila-treated group, suggesting a beneficial modulation of the gut microbiome associated with the supplementation.
Our findings declared that A. muciniphila supplementation alleviates gastrointestinal inflammation through IL-6/STAT3 signaling pathway. This protective effect was mediated by the downregulation of the IL-6 and STAT3, highlighting a potential mechanism by which A. muciniphila modulates inflammatory responses. This work disclosed that A. muciniphila demonstrates a defensive influence against TNBS-induced enteritis in vivo, proposing it qualified as a unique therapeutic focusing on modulating IL-6, STAT3, or p-STAT3 in the treatment of colitis.
炎症性肠病是一种影响肠道的慢性炎症性疾病。本研究旨在探讨嗜黏蛋白阿克曼氏菌的相对丰度是否与IL6/STAT3信号通路相关，以及嗜黏蛋白阿克曼氏菌在三硝基苯磺酸（TNBS）诱导的肠炎小鼠模型中的基本分子机制，包括IL6/STAT3信号通路中炎性细胞因子和蛋白质的表达。
通过黏膜活检和粪便样本研究嗜黏蛋白阿克曼氏菌与IL6/STAT3之间的关联。采用TNBS诱导的结肠炎小鼠模型来阐明潜在机制。通过16s rRNA测序分析肠道微生物群的变化。
在克罗恩病患者中，STAT3和IL-6水平与嗜黏蛋白阿克曼氏菌呈负相关。在A.m+TNBS组中，IL-6、p-STAT3和STAT3的表达下调，表明嗜黏蛋白阿克曼氏菌可能在体内抑制TNBS诱导的肠炎中的IL6/STAT3信号通路。为了研究补充嗜黏蛋白阿克曼氏菌在TNBS诱导的肠炎体内的潜在保护作用，进行16S rRNA测序以分析肠道微生物群组成的变化。结果显示，嗜黏蛋白阿克曼氏菌治疗组的微生物多样性和丰度显著增加，表明补充该菌对肠道微生物群有有益的调节作用。
我们的研究结果表明，补充嗜黏蛋白阿克曼氏菌可通过IL-6/STAT3信号通路减轻胃肠道炎症。这种保护作用是由IL-6和STAT3的下调介导的，突出了嗜黏蛋白阿克曼氏菌调节炎症反应的潜在机制。这项研究表明，嗜黏蛋白阿克曼氏菌在体内对TNBS诱导的肠炎具有防御作用，表明它有资格作为一种独特的治疗方法，专注于调节IL-6、STAT3或p-STAT3来治疗结肠炎。
