Background and aims

Gut microbiota and their metabolic products might play important roles in regulating the pathogenesis of choledocholithiasis concurrent with cholangitis (CC). The aim of this study was to explore the characteristic gut dysbiosis, metabolite profiles and the possible roles in patients with CC.

Methods

A case–control study was carried out to analyze the alterations in the intestinal microbiota and their metabolites in patients with CC (n = 25) compared with healthy controls (HCs) (n = 25) by metagenomic sequencing to define the gut microbiota community and liquid chromatography/mass spectrometry (LC/MS) analysis to characterize the metabolite profiles.

Results

Significantly reduced Shannon diversity index (p = 0.043) and differential overall fecal microbiota community in CCs were observed. Twelve dominant altered species were identified and analyzed (LDA score > 3.0, p < 0.05) (Q value < 0.05), including unclassified_f_Enterobacteriaceae, Escherichia_coli, Roseburia_faecis and Eubacterium rectale. Moreover, the levels of KEGG pathways related to biofilm formation of Escherichia coli, lipopolysaccharide (LPS) biosynthesis, and the metabolism of propanoate and glutathione in CCs were significantly altered. Finally, 47 markedly changed metabolites (VIP > 1.0 and p < 0.05), including low level of kynurenic acid (KYNA) and high concentration of N-palmitoylsphingosine involving tryptophan metabolism and sphingolipid signaling pathways, were identified to validate aberrant metabolic patterns in CCs, and multiple correlated metabolic modules involving bile inflammation were altered in CCs.

Conclusion

Our study provides novel insights into compositional and functional alterations in the gut microbiome and metabolite profiles in CC and the underlying mechanisms between gut microbiota and bile inflammation.

中文翻译：

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胆总管结石合并胆管炎肠道微生物组和代谢物谱的改变

背景和目标

肠道菌群及其代谢产物可能在调节胆总管结石并发胆管炎 (CC) 的发病机制中发挥重要作用。本研究的目的是探讨 CC 患者的特征性肠道菌群失调、代谢物谱和可能的作用。

方法

 进行了一项病例对照研究，通过宏基因组测序分析CC 患者（n  = 25）与健康对照组（HC）（n = 25）相比肠道微生物群及其代谢物的变化，以确定肠道微生物群落和液相色谱/质谱 (LC/MS) 分析以表征代谢物谱。

结果

观察到显着降低的香农多样性指数 ( p  = 0.043) 和 CCs 中的总体粪便微生物群落差异。鉴定和分析了 12 个显性变异物种（LDA 评分 > 3.0，p  < 0.05）（Q值 < 0.05），包括unclassified_f_Enterobacteriaceae、Escherichia_coli、Roseburia_faecis和Eubacterium rectale 。此外，与大肠杆菌生物膜形成、脂多糖 (LPS) 生物合成以及 CCs 中丙酸和谷胱甘肽代谢相关的 KEGG 通路水平显着改变。最后，47 种显着变化的代谢物（VIP > 1.0 和p < 0.05)，包括低水平的犬尿酸 (KYNA) 和高浓度的涉及色氨酸代谢和鞘脂信号通路的 N-棕榈酰鞘氨醇，被确定以验证 CCs 中的异常代谢模式，并且涉及胆汁炎症的多个相关代谢模块在 CCs 中发生了改变.

结论

我们的研究为 CC 中肠道微生物组和代谢物谱的组成和功能改变以及肠道微生物群和胆汁炎症之间的潜在机制提供了新的见解。