Accumulation of bile acids (BAs) contributes significantly to the pathogenesis of primary biliary cholangitis (PBC). Here, we sought to systematically characterize the serum and fecal BA profiles and the linkage between BAs and gut microbiota in PBC. The serum and fecal BAs were compared between 65 UDCA treatment-naive PBC and 109 healthy controls using UPLC-MS in cross-sectional study. In a prospective study, a subgroup of patients was enrolled for BA and microbiota analysis before and after UDCA therapy. BA compositions in serum and feces significantly differed between treatment-naive PBC and controls. Particularly, PBC was associated with decreased conversions of conjugated to unconjugated, and primary to secondary BAs, indicating impaired microbial metabolism of BAs. PBC patients at advanced stage exhibited a more abnormal BA profile compared with early-stage patients. UDCA treatment led to a decreased level of taurine-conjugated BAs, thereby reversing the conjugated/unconjugated ratio in PBC. Moreover, the level of secondary BAs such as DCA and conjugated DCA inversely correlated with PBC-enriched gut microbes (e.g., Veillonella, Klebsiella), while positively correlated with control-enriched microbes (e.g., Faecalibacterium, Oscillospira). Microbiota analysis also revealed a significant increase of taurine-metabolizing bacteria Bilophila spp. in patients after UDCA, which was strongly correlated with decreased taurine-conjugated BAs. In addition, serum FGF19 was remarkably increased in treatment-naïve PBC and decreased after UDCA. Our study established specific alterations of BA compositions in serum and feces of PBC, suggesting the potential for using BAs for diagnosis, and highlighting the possibility of modulating BA profile by altering gut microbiota. Graphical Abstract.

中文翻译：

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对原发性胆源性胆管炎的血清和粪便胆汁酸谱及其与肠道菌群的相互作用进行综合分析。

胆汁酸（BAs）的积累在原发性胆源性胆管炎（PBC）的发病机理中起重要作用。在这里，我们试图系统地表征血清和粪便BA谱以及BA和PBC中肠道菌群之间的联系。使用UPLC-MS在横断面研究中比较了65例未接受UDCA治疗的PBC和109例健康对照组的血清和粪便BA。在一项前瞻性研究中，在UDCA治疗前后，对亚组患者进行了BA和微生物群分析。初治的PBC和对照组之间血清和粪便中的BA组成存在显着差异。特别地，PBC与结合的BAs转化为未结合的BAs，以及初级BAs到继发BAs的转化减少有关，表明BAs的微生物代谢受损。与早期患者相比，晚期PBC患者表现出更多的BA异常。UDCA处理导致牛磺酸结合的BA的水平降低，从而逆转了PBC中的结合/未结合比例。此外，次要BAs的水平，例如DCA和结合的DCA与富含PBC的肠道微生物（例如Veillonella，Klebsiella）呈负相关，而与富含对照的微生物（例如Faecalibacterium，Oscillospira）呈正相关。微生物群分析还显示，牛磺酸代谢细菌Bilophila spp显着增加。UDCA后的患者中，这与牛磺酸缀合的BA降低密切相关。此外，未治疗的PBC中血清FGF19显着增加，而UDCA后则降低。我们的研究建立了PBC血清和粪便中BA组成的特定变化，表明使用BA进行诊断的潜力，并强调了通过改变肠道菌群来调节BA谱的可能性。图形概要。