Qiu Min, Geng Huafeng, Zou Chenyu, Zhao Xiaotong, Zhao Caijun, Xie Jiaxin, Wang Jinnan, Zhang Naisheng, Hu Yubo, Fu Yunhe, Wang Junrong, Hu Xiaoyu
Department of Gynecology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China; Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province 130062, China.
Department of Gynecology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.
Int Immunopharmacol. 2025 Jan 27;146:113919. doi: 10.1016/j.intimp.2024.113919. Epub 2024 Dec 29.
Endometritis poses higher health risks to women. Clinical practice has found that gastrointestinal dysfunction is more likely to lead to the occurrence of endometritis. However, the mechanism is unclear. This study explored the influence and mechanism of DSS-induced intestinal inflammation on endometritis. Our findings demonstrate that DSS-induced intestinal inflammation can worsen LPS-induced endometritis in mice, and this effect is dependent on the gut microbiota, as depleting the gut microbiota eliminates this protective effect. Similarly, FMT from DSS-treated mice to recipient mice exacerbates LPS-induced endometritis. In addition, treatment of DSS disrupted an imbalance of succinate-producing and succinate-consuming bacteria and increased the levels of succinate in the gut and uterine tissues. Furthermore, treatment with succinate aggravates LPS-induced endometritis by activating the succinate receptor 1 (SUCNR1), evidenced by inhibition of the activation of SUCNR1 reversed the inflammatory response in uterine tissues induced by succinate during endometritis induced by LPS. Collectively, the results suggested that dysbiosis of the gut microbiota exacerbates LPS-induced endometritis by production and migration of succinate from gut to uterine tissues via the gut-uterus axis, then activates the SUCNR1. This identifies gut-derived succinate as a novel target for treating endometritis, and it indicates that targeting the gut microbiota and its metabolism could be a potential strategy for intervention in endometritis.
子宫内膜炎对女性健康构成更高风险。临床实践发现，胃肠功能障碍更易导致子宫内膜炎的发生。然而，其机制尚不清楚。本研究探讨了葡聚糖硫酸钠（DSS）诱导的肠道炎症对子宫内膜炎的影响及其机制。我们的研究结果表明，DSS诱导的肠道炎症会加重脂多糖（LPS）诱导的小鼠子宫内膜炎，且这种作用依赖于肠道微生物群，因为清除肠道微生物群可消除这种保护作用。同样，将DSS处理小鼠的粪便微生物群移植（FMT）到受体小鼠会加重LPS诱导的子宫内膜炎。此外，DSS处理会破坏产琥珀酸菌和消耗琥珀酸菌的失衡，并增加肠道和子宫组织中琥珀酸的水平。此外，琥珀酸处理通过激活琥珀酸受体1（SUCNR1）加重LPS诱导的子宫内膜炎，LPS诱导的子宫内膜炎期间，抑制SUCNR1的激活可逆转琥珀酸诱导的子宫组织炎症反应，这证明了上述观点。总体而言，结果表明肠道微生物群失调通过琥珀酸经肠-子宫轴从肠道向子宫组织的产生和迁移加重LPS诱导的子宫内膜炎，进而激活SUCNR1。这确定了肠道来源的琥珀酸是治疗子宫内膜炎的新靶点，并表明针对肠道微生物群及其代谢可能是干预子宫内膜炎的潜在策略。
