Abstract：
OBJECTIVE: Primary choledocholithiasis is a common digestive disease with high morbidity and relapse. However, the compositions and functions of the bile microbial ecosystem and the pathogenesis of microfloral regulation of host metabolism resulting in stone formation are poorly understood.
METHODS: Biliary samples collected from patients with acute cholangitis induced by benign biliary stricture (nonlithiasis group, n = 17) and primary choledocholithiasis (lithiasis group, n = 33) were subjected to multiomics analyses. Furthermore, clinicopathological features collected over a 24-month follow-up period were examined to evaluate the predictive value of candidate microbes.
RESULTS: Five alpha diversity indices of the bile microbiome were significantly decreased in the lithiasis group. Furthermore, we identified 49 differential bile flora between the two groups, and the relative abundances of 6 bacteria, Actinobacteria, Actinobacteriota, Staphylococcales, Micrococcales, Altererythrobacter and Carnobacteriaceae, were associated with primary choledocholithiasis relapse conditions. Multiomics analyses showed that specific changes in disease-related bacterial taxa were closely related to metabolite variation (low-molecular weight carboxylic acids, sterol liquid and acylcarnitine), which might reflect disease prognosis. According to microbiomic and metabolomic pathway analyses, we revealed that bacterial infections, microbiota-derived amino acid metabolites and secondary bile acid-related pathways were significantly enriched in the stone-formation group, suggesting a novel host-microbial metabolic mechanism of primary choledocholithiasis.
CONCLUSIONS: Our study first indicates bile host-microbial dysbiosis modulates the abnormal accumulation of metabolites might further disrupt calcium homeostasis and generate insoluble saponification. Additionally, we determined the predictive value of Actinomycetes phylum reduction for recurrence in primary common bile duct stone patients.
METHODS: Biliary samples collected from patients with acute cholangitis induced by benign biliary stricture (nonlithiasis group, n = 17) and primary choledocholithiasis (lithiasis group, n = 33) were subjected to multiomics analyses. Furthermore, clinicopathological features collected over a 24-month follow-up period were examined to evaluate the predictive value of candidate microbes.
RESULTS: Five alpha diversity indices of the bile microbiome were significantly decreased in the lithiasis group. Furthermore, we identified 49 differential bile flora between the two groups, and the relative abundances of 6 bacteria, Actinobacteria, Actinobacteriota, Staphylococcales, Micrococcales, Altererythrobacter and Carnobacteriaceae, were associated with primary choledocholithiasis relapse conditions. Multiomics analyses showed that specific changes in disease-related bacterial taxa were closely related to metabolite variation (low-molecular weight carboxylic acids, sterol liquid and acylcarnitine), which might reflect disease prognosis. According to microbiomic and metabolomic pathway analyses, we revealed that bacterial infections, microbiota-derived amino acid metabolites and secondary bile acid-related pathways were significantly enriched in the stone-formation group, suggesting a novel host-microbial metabolic mechanism of primary choledocholithiasis.
CONCLUSIONS: Our study first indicates bile host-microbial dysbiosis modulates the abnormal accumulation of metabolites might further disrupt calcium homeostasis and generate insoluble saponification. Additionally, we determined the predictive value of Actinomycetes phylum reduction for recurrence in primary common bile duct stone patients.
摘要：
目的：原发性胆总管结石是一种常见的消化系统疾病，发病率高，复发率高。然而,胆汁微生物生态系统的组成和功能以及导致结石形成的宿主代谢的微花调节的发病机理知之甚少。
方法：从良性胆管狭窄引起的急性胆管炎患者（非结石组，n=17）和原发性胆总管结石（结石组，n=33)进行多组学分析。此外，对24个月随访期间收集的临床病理特征进行检查，以评估候选微生物的预测价值。
结果：结石组胆汁微生物组的5个α多样性指数显著降低。此外，我们确定了两组之间49种不同的胆汁菌群，和6种细菌的相对丰度，放线菌,放线菌,葡萄球菌,微球菌,变温杆菌和肉芽胞杆菌科，与原发性胆总管结石复发有关。多组学分析表明，疾病相关细菌分类群的特定变化与代谢物变异密切相关（低分子量羧酸，甾醇液体和酰基肉碱)，这可能反映疾病的预后。根据微生物组学和代谢组学途径分析，我们发现细菌感染，在结石形成组中，微生物来源的氨基酸代谢产物和次级胆汁酸相关通路显著富集，提示原发性胆总管结石的一种新的宿主微生物代谢机制。
结论：我们的研究首先表明胆汁宿主微生物菌群失调调节代谢物的异常积累可能进一步破坏钙稳态并产生不溶性皂化。此外,我们确定了放线菌门减少对原发性胆总管结石患者复发的预测价值。
方法：从良性胆管狭窄引起的急性胆管炎患者（非结石组，n=17）和原发性胆总管结石（结石组，n=33)进行多组学分析。此外，对24个月随访期间收集的临床病理特征进行检查，以评估候选微生物的预测价值。
结果：结石组胆汁微生物组的5个α多样性指数显著降低。此外，我们确定了两组之间49种不同的胆汁菌群，和6种细菌的相对丰度，放线菌,放线菌,葡萄球菌,微球菌,变温杆菌和肉芽胞杆菌科，与原发性胆总管结石复发有关。多组学分析表明，疾病相关细菌分类群的特定变化与代谢物变异密切相关（低分子量羧酸，甾醇液体和酰基肉碱)，这可能反映疾病的预后。根据微生物组学和代谢组学途径分析，我们发现细菌感染，在结石形成组中，微生物来源的氨基酸代谢产物和次级胆汁酸相关通路显著富集，提示原发性胆总管结石的一种新的宿主微生物代谢机制。
结论：我们的研究首先表明胆汁宿主微生物菌群失调调节代谢物的异常积累可能进一步破坏钙稳态并产生不溶性皂化。此外,我们确定了放线菌门减少对原发性胆总管结石患者复发的预测价值。
