Xi Chen, Xin Chen, Ding Yan, Na Zhang, Wen Fu, Meixuan Wu, Feifei Ge, Jiangtuan Wang, Xiaofen Li, Meiyu Geng, Jinheng Wang, Daolin Tang, Jinbao Liu
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引用次数: 0
摘要
尽管最近取得了一些进展,但重症急性胰腺炎(SAP)仍然是一种致命的炎症,治疗方法有限。在这里,我们提供了令人信服的证据,证明抗阿尔茨海默氏症药物 GV-971(低聚甘露酸钠)在各种雄性小鼠 SAP 模型中具有保护作用。微生物组测序以及肠道微生物群移植和质谱技术揭示,GV-971 能重塑肠道微生物群,增加粪杆菌数量,调节外周和肠道免疫系统。对经 GV-971 处理的 SAP 小鼠盲肠内容物进行的代谢组学分析进一步确定,丙酸和丁酸等短链脂肪酸是通过阻断 MAPK 通路抑制巨噬细胞 M1 极化和随后致命炎症的关键代谢物。这些研究结果表明,GV-971 可通过靶向微生物群代谢免疫轴来治疗 SAP。
GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis
Despite recent advances, severe acute pancreatitis (SAP) remains a lethal inflammation with limited treatment options. Here, we provide compelling evidence of GV-971 (sodium oligomannate), an anti-Alzheimer’s medication, as being a protective agent in various male mouse SAP models. Microbiome sequencing, along with intestinal microbiota transplantation and mass cytometry technology, unveil that GV-971 reshapes the gut microbiota, increasing Faecalibacterium populations and modulating both peripheral and intestinal immune systems. A metabolomics analysis of cecal contents from GV-971–treated SAP mice further identifies short-chain fatty acids, including propionate and butyrate, as key metabolites in inhibiting macrophage M1 polarization and subsequent lethal inflammation by blocking the MAPK pathway. These findings suggest GV-971 as a promising therapeutic for SAP by targeting the microbiota metabolic immune axis.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.