Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Disease, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
Nat Commun. 2024 Sep 27;15(1):8278. doi: 10.1038/s41467-024-52398-z.
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.
尽管最近取得了进展，但重症急性胰腺炎 (SAP) 仍然是一种致命的炎症，治疗选择有限。在这里，我们提供了令人信服的证据，表明抗阿尔茨海默病药物 GV-971（甘露寡糖酸钠）是各种雄性小鼠 SAP 模型中的一种保护剂。微生物组测序，以及肠道微生物群移植和质谱流式细胞术技术，揭示了 GV-971 重塑了肠道微生物群，增加了粪杆菌种群，并调节了外周和肠道免疫系统。对 GV-971 治疗 SAP 小鼠的盲肠内容物进行代谢组学分析，进一步确定了短链脂肪酸，包括丙酸和丁酸，作为通过阻断 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。这些发现表明 GV-971 通过靶向微生物群代谢免疫轴成为 SAP 的一种有前途的治疗方法。
