Center for Global Health, School of Public Health, Nanjing Medical, University, 101 Longmian Avenue, Nanjing, Jiangsu 211166, PR China.
Center for Global Health, School of Public Health, Nanjing Medical, University, 101 Longmian Avenue, Nanjing, Jiangsu 211166, PR China; Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu 211166, PR China.
Biochim Biophys Acta Mol Basis Dis. 2022 Mar 1;1868(3):166320. doi: 10.1016/j.bbadis.2021.166320. Epub 2021 Dec 10.
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by bile duct inflammation, fibrosis, bile acid (BA) metabolism disorders and gut microbiota dysbiosis. At present, the aetiology and pathogenesis of PSC are not clear, and there is no specific or effective treatment available. Therefore, new research perspectives are needed to explore effective methods to treat PSC and improve symptoms. The intestinal microbiota of patients with PSC is known to be significantly different from that of healthy people. By comparing differentially abundant bacterial genera in PSC patients, it was found that the abundance of Prevotella copri (P. copri) was significantly decreased, suggesting that this species may have a protective effect against PSC disease. Therefore, comprehensively exploring the role and possible function of P. copri in the disease process is worthwhile. In this study, a PSC mouse model was established by feeding mice a customized diet supplemented with 0.1% (w/w) 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for one week, and the abundance of P. copri was confirmed to be decreased in this model. Previous studies in patients and animal models have demonstrated that gut microbiota intervention is an acceptable treatment for some diseases. We found that intervention with P. copri could significantly improve cholestasis and liver fibrosis by enhancing the FXR-related signalling pathway in PSC mice. Together, through the overall effect of P. copri on intestinal microbiota structure and its association with BAs, we speculate that P. copri intervention might be as potential biological treatment of PSC.
原发性硬化性胆管炎（PSC）是一种慢性胆汁淤积性肝病，其特征为胆管炎症、纤维化、胆汁酸（BA）代谢紊乱和肠道微生物群落失调。目前，PSC 的病因和发病机制尚不清楚，也没有特定的或有效的治疗方法。因此，需要新的研究视角来探索治疗 PSC 和改善症状的有效方法。PSC 患者的肠道微生物群与健康人群有显著差异。通过比较 PSC 患者中差异丰富的细菌属，发现普雷沃氏菌属（Prevotella copri，P. copri）的丰度明显降低，表明该物种可能对 PSC 疾病具有保护作用。因此，全面探索 P. copri 在疾病过程中的作用和可能的功能是值得的。在这项研究中，通过给小鼠喂食含有 0.1%（w/w）3,5-二乙氧羰基-1,4-二氢吡啶（DDC）的定制饮食，建立了 PSC 小鼠模型，证实该模型中 P. copri 的丰度降低。先前在患者和动物模型中的研究表明，肠道微生物群干预是治疗某些疾病的一种可接受的方法。我们发现，通过增强 PSC 小鼠的 FXR 相关信号通路，P. copri 的干预可以显著改善胆汁淤积和肝纤维化。总之，通过 P. copri 对肠道微生物群落结构的整体影响及其与 BAs 的关联，我们推测 P. copri 的干预可能是 PSC 的潜在生物治疗方法。
