Altered faecal microbiome and metabolome in IgG4-related sclerosing cholangitis and primary sclerosing cholangitis
Altered faecal microbiome and metabolome in IgG4-related sclerosing cholangitis and primary sclerosing cholangitis
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IgG4相关硬化性胆管炎和原发性硬化性胆管炎中粪便微生物组和代谢组的改变
DOI：
10.1136/gutjnl-2020-323565
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发表时间：
2021-05-24
期刊：
影响因子：
24.5
通讯作者：
Tang, Ruqi
中科院分区：
文献类型：
--
作者：
Liu, Qiaoyan;Li, Bo;Tang, Ruqi
目的IgG 4相关性硬化性胆管炎（IgG 4-SC）与原发性硬化性胆管炎（PSC）之间存在多种临床相似性，虽然PSC中肠道菌群失调已被广泛研究，但肠道菌群在IgG 4-SC中的作用仍不清楚。在此，我们旨在评估IgG 4-SC和PSC中肠道微生物组和代谢组的改变。我们对来自135名IgG 4-SC（n=34）、PSC（n=37）和健康对照（n=64）受试者的粪便样品进行16 S rRNA基因扩增子测序。还对样本子集（31份IgG 4-SC、37份PSC和45份对照）进行了非靶向代谢组学分析。结果与对照组相比，IgG 4-SC和PSC中α多样性降低，微生物群落发生变化。这些变化伴随着粪便代谢组的差异。重要的是，尽管微生物群组成和代谢活性存在一些常见的变化，但综合分析在IgG 4-SC和PSC中鉴定了不同的宿主-微生物关联。与疾病相关的属和代谢产物往往与IgG 4-SC中的转氨酶相关。在IgG 4-SC中，布劳特氏菌的显著消耗和琥珀酸的升高可能是肝脏炎症的基础。相比之下，在PSC中检测到微生物或代谢特征与胆汁淤积参数之间的潜在联系。特别是，真杆菌和微生物衍生的代谢产物，包括次级胆汁酸的一致减少，涉及PSC胆汁淤积的新宿主微生物代谢途径。有趣的是，基于代谢物的预测模型在区分疾病状态方面比基于微生物的预测模型更有效。结论IgG 4-SC和PSC具有不同的宿主-微生物相互作用，可能参与疾病的发病机制。这些数据强调了IgG 4-SC的独特性。
Objective Multiple clinical similarities exist between IgG4-related sclerosing cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC), and while gut dysbiosis has been extensively studied in PSC, the role of the gut microbiota in IgG4-SC remains unknown. Herein, we aimed to evaluate alterations of the gut microbiome and metabolome in IgG4-SC and PSC. Design We performed 16S rRNA gene amplicon sequencing of faecal samples from 135 subjects with IgG4-SC (n=34), PSC (n=37) and healthy controls (n=64). A subset of the samples (31 IgG4-SC, 37 PSC and 45 controls) also underwent untargeted metabolomic profiling. Results Compared with controls, reduced alpha-diversity and shifted microbial community were observed in IgG4-SC and PSC. These changes were accompanied by differences in stool metabolomes. Importantly, despite some common variations in the microbiota composition and metabolic activity, integrative analyses identified distinct host-microbe associations in IgG4-SC and PSC. The disease-associated genera and metabolites tended to associate with the transaminases in IgG4-SC. Notable depletion of Blautia and elevated succinic acid may underlie hepatic inflammation in IgG4-SC. In comparison, potential links between the microbial or metabolic signatures and cholestatic parameters were detected in PSC. Particularly, concordant decrease of Eubacterium and microbiota-derived metabolites, including secondary bile acids, implicated novel host-microbial metabolic pathways involving cholestasis of PSC. Interestingly, the predictive models based on metabolites were more effective in discriminating disease status than those based on microbes. Conclusions Our data reveal that IgG4-SC and PSC possess divergent host-microbe interplays that may be involved in disease pathogenesis. These data emphasise the uniqueness of IgG4-SC.