Multiple mechanisms for the gut microbiome contributing to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) have been implicated. Here, weaim to investigate the contribution and potential application for altered bile acids (BA) metabolizing microbesin NAFLD by post-hoc analysis of whole metagenome sequencing (WMS) data. The discovery cohort consisted of 86 well-characterized biopsy-proven NAFLD patients and 38 healthy controls. Assembly-based analysis was performed to identify BA-metabolizing microbes. Statistical tests, feature selection and microbial co-abundance analysis were integrated to identify microbial alterations and markers in NAFLD. An independent validation cohort was subjected to similar analyses. NAFLD microbiota exhibited decreased diversity and microbial associations. We established a classifier model with 53 differential species exhibiting a robust diagnostic accuracy (AUC=0.97) for dectecting NAFLD. Next, eight important differential pathway markers including secondary BA biosynthesis were identified. Specifically, increased abundance of 7α-HSDH, baiA and baiB were detected in NAFLD. Further, 10 of 50 BA-metabolizing metagenome-assembled genomes (MAGs) from Bacteroides ovatusand Eubacterium biforme, were dominant in NAFLD and interplayed as a synergetic ecological guild. Importantly, two subtypes of NAFLD patients were observed according to secondary BA metabolism potentials. Elevated capability for secondary BA biosynthesis was also observed in the validation cohort. These bacterial BA-metabolizing genes and microbes identified in this study may serve as disease markers. Microbial differences in BA-metabolism and strain-specific differences among patients highlight the potential for precision medicine in NAFLD treatment.

中文翻译：

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改变胆汁酸代谢肠道微生物群和特定胆汁酸基因作为 NAFLD 细分的精准药物

肠道微生物群导致非酒精性脂肪性肝病 (NAFLD) 发病机制的多种机制已被牵连。在这里，我们旨在通过对全宏基因组测序 (WMS) 数据的事后分析来研究改变的胆汁酸 (BA) 代谢 NAFLD 微生物的贡献和潜在应用。发现队列由 86 名经过充分活检证实的 NAFLD 患者和 38 名健康对照组成。进行基于组装的分析以鉴定 BA 代谢微生物。统计测试、特征选择和微生物共丰度分析被整合以识别 NAFLD 中的微生物改变和标志物。一个独立的验证队列进行了类似的分析。NAFLD 微生物群的多样性和微生物关联性降低。我们建立了一个具有 53 个不同物种的分类模型，在检测 NAFLD 时表现出强大的诊断准确性 (AUC=0.97)。接下来，确定了包括次级 BA 生物合成在内的 8 个重要的差异途径标志物。具体来说，在 NAFLD 中检测到 7α-HSDH、baiA 和 baiB 的丰度增加。此外，来自卵形拟杆菌和双形真杆菌的 50 个 BA 代谢宏基因组组装基因组 (MAGs) 中有 10 个在 NAFLD 中占主导地位，并作为一个协同生态协会相互作用。重要的是，根据继发性 BA 代谢潜能观察到两种 NAFLD 患者亚型。在验证队列中也观察到二次 BA 生物合成能力的提高。本研究中鉴定的这些细菌 BA 代谢基因和微生物可作为疾病标志物。