Zhiyuan Hao1, Kegong Tao1, Kaiming Wu1, Yuanyuan Luo2, Yiting Lu2, Binbin Li3, Peimei Shi1, Peiqin Wang1, Xin Zeng4,5, Yong Lin6,7. 1. Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China. 2. Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China. 3. Department of Pathology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China. 4. Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China. zengxinmd1978@163.com. 5. Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China. zengxinmd1978@163.com. 6. Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, China. linyongmd@163.com. 7. Department of Gastroenterology, Shanghai Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, China. linyongmd@163.com.
Abstract
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.
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.