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Background: Clonorchis sinensis (C. sinensis) is a epidemiologically significant food-borne parasite, causing several hepatobiliary diseases. Biliary microbiota community structure might be influenced by infection with pathogens. However, the biliary microbiome of biliary obstruction patients infected with C. sinensis is still an unexplored aspect. Methods: A total of 50 biliary obstruction patients were enrolled, including 24 infected with C. sinensis and 26 non-infected subjects. The bile samples were collected by Endoscopic Retrograde Cholangiopancretography. Biliary microbiota alteration was analyzed through high-throughput 16S ribosomal RNA (rRNA) gene sequencing. Results: Our findings revealed that there was significant increase in both richness and diversity, as well as changes in the taxonomic composition of the biliary microbiota of C. sinensis infected patients. At the phylum level, C. sinensis infection induced Proteobacteria increased and Firmicutes reduced. At the genus level, the relative abundance of Pseudomonas and Staphylococcus increased significantly, while Enterococcus decreased prominently in infected groups (P < 0.05). The PICRUSt analysis further showed remarkably different metabolic pathways between the two groups. Conclusion: C. sinensis infection could modify the biliary microbiota, increasing the abundance and changing the phylogenetic composition of bacterial in biliary obstruction patients. This study may help deepen the understanding of the host-biliary microbiota interplay with C. sinensis infection on the background of biliary obstruction and provide new insights into understanding the pathogenesis of clonorchiasis. [ABSTRACT FROM AUTHOR]

Pancreatic surgery is characterized by high morbidity and mortality. Biliary colonization may affect clinical outcomes in these patients. This study aimed to verify whether bacteriobilia and multidrug resistance (MDR) detected during and after pancreatic surgery may have an impact on post-operative outcomes. Data from patients undergoing pancreatic surgery involving bile duct transection (2016-2022) in two high-volume centers were analyzed in relationship to overall morbidity, major morbidity and mortality after pancreato-duodenectomy (PD) or total pancreatectomy (TP). Simple and multivariable regressions were used. 227 patients submitted to PD (n=129) or TP (n=98) were included. Of them, 133 had preoperative biliary drainage (BD; 56.6%), mostly with the employment of endoscopic stents (91.7%). Bacteriobilia was detected in 111 patients (48.9%), and remarkably, observed in patients with BD (p=0.001). In addition, 25 MDR pathogens were identified (22.5%), with a significant prevalence in patients with BD. Multivariable regression analysis showed BD was strongly related to MDR isolation (odds ratio [OR]: 5.61; p=0.010). MDR isolation was the main factor linked to a higher number of major complications (OR: 2.75; p=0.041), including major infection complications (OR: 2.94; p=0.031). Isolation of MDR from biliary swab during PD or TP significantly increases the risk of a worse post-operative outcome. Pre-operative precautions could improve patient safety. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA), a highly heterogeneous cancer, is the second most common type of primary liver cancer. It is characterized by resistance to therapy and poor prognosis, with a 5-year survival rate lower than 20%. The pathogenesis of CCA is complex and multifactorial, and in recent years, bile acids (BAs) have been implicated in CCA development and prognosis. BAs belong to a category of amphipathic compounds that hold significant importance as signaling molecules and inflammatory agents. They possess the ability to activate transcriptional factors and cellular signaling pathways, thereby governing the regulation of lipid, glucose, and energy metabolism in diverse human disorders. These disorders encompass chronic liver diseases among other conditions. In this review, we provided an update on the current knowledge on the molecular mechanisms involving BAs in cholangiocarcinogenesis. Additionally, we analyzed the role of gut and biliary microbiota in CCA pathogenesis. Future research is required to better understand how to modulate BA activity and, possibly, identify new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Clonorchis sinensis is a zoonotic liver fluke that inhabits the bile ducts of the human liver for prolonged periods, leading to cholangiocarcinoma. Recent research indicates associations between altered biliary microbiota and bile duct disorders. However, the impacts of C. sinensis infection on bile duct epithelium and subsequent effects on biliary microbiota remain unknown. Methods: Feline bile duct samples were collected from both uninfected and C. sinensis-infected cats. Histopathological examination was performed to assess epithelial changes, fibrosis, mucin and cell proliferation using hematoxylin-eosin staining and immunohistochemistry. Additionally, biliary microbiota composition was analyzed through 16S rRNA gene sequencing. Statistical analyses were conducted to compare the microbial diversity and relative abundance between infected and uninfected samples. Results: Histopathological analysis of infected feline bile ducts revealed prominent epithelial hyperplasia characterized by increased cell proliferation. Moreover, periductal fibrosis and collagen fibrosis were observed in infected samples compared to uninfected controls. Biliary microbial richness decreased with disease progression compared to uninfected controls. Streptococcus abundance positively correlated with disease severity, dominating communities in cancer samples. Predictive functional analysis suggested that C. sinensis may promote bile duct lesions by increasing microbial genes for carbohydrate metabolism, replication, and repair. Conclusions: This study provides comprehensive insights into the pathological effects of C. sinensis infection on feline bile duct epithelium and its influence on biliary microbiota composition. These novel findings provide insight into C. sinensis pathogenesis and could inform therapeutic development against human clonorchiasis. Further research is warranted to elucidate the underlying mechanisms driving these changes and their implications for host-parasite interactions.

Cholangiocarcinoma (CCA), a highly heterogeneous cancer, is the second most common type of primary liver cancer. It is characterized by resistance to therapy and poor prognosis, with a 5-year survival rate lower than 20%. The pathogenesis of CCA is complex and multifactorial, and in recent years, bile acids (BAs) have been implicated in CCA development and prognosis. BAs belong to a category of amphipathic compounds that hold significant importance as signaling molecules and inflammatory agents. They possess the ability to activate transcriptional factors and cellular signaling pathways, thereby governing the regulation of lipid, glucose, and energy metabolism in diverse human disorders. These disorders encompass chronic liver diseases among other conditions. In this review, we provided an update on the current knowledge on the molecular mechanisms involving BAs in cholangiocarcinogenesis. Additionally, we analyzed the role of gut and biliary microbiota in CCA pathogenesis. Future research is required to better understand how to modulate BA activity and, possibly, identify new therapeutic strategies.

Introduction: Cholelithiasis has a high incidence worldwide and limited treatment options due to its poorly understood pathogenesis. Furthermore, the role of biliary microbiota in cholelithiasis remains understudied. To address these questions, we performed microbial sequencing from biliary samples from primary bile duct stone (PBDS) and secondary bile duct stone (SBDS) patients. Results: We analyzed in total 45 biliary samples, including those from cholelithiasis patients with PBDS or SBDS and people with other digestive diseases. 16S rRNA sequencing showed the bacteria family Alcaligenaceae increased in relative abundance in the lithiasis group compared with the non-lithiasis group. In addition, the PBDS group showed significantly lower bacterial diversity than SBDS, with Propionibacteriaceae, Sphingomonadaceae, and Lactobacillaceae as the most significant bacteria families decreased in relative abundance. We further performed whole metagenomic shotgun sequencing (wMGS) and found increased ability of biofilm synthesis and the ability to sense external stimuli in PBDS based on functional annotation of mapped reads. From genome-resolved analysis of the samples, we identified 36 high-quality draft bacterial genome sequences with completion ≥70% and contamination ≤10%. Most of these genomes were classified into Proteobacteria, Firmicutes, or Actinobacteria. Conclusions: Our findings indicated that there is a subtle impact on biliary microbiome from cholelithiasis while the difference is more pronounced between the PBDS and SBDS. It was revealed that the diversity of biliary microbiota in PBDS is lower, while some metabolic pathways are up-regulated, including those linked to higher incidence of different types of cancer, providing new insights for the understanding of cholelithiasis with different origin. [ABSTRACT FROM AUTHOR]

IntroductionCholelithiasis has a high incidence worldwide and limited treatment options due to its poorly understood pathogenesis. Furthermore, the role of biliary microbiota in cholelithiasis remains understudied. To address these questions, we performed microbial sequencing from biliary samples from primary bile duct stone (PBDS) and secondary bile duct stone (SBDS) patients.ResultsWe analyzed in total 45 biliary samples, including those from cholelithiasis patients with PBDS or SBDS and people with other digestive diseases. 16S rRNA sequencing showed the bacteria family Alcaligenaceae increased in relative abundance in the lithiasis group compared with the non-lithiasis group. In addition, the PBDS group showed significantly lower bacterial diversity than SBDS, with Propionibacteriaceae, Sphingomonadaceae, and Lactobacillaceae as the most significant bacteria families decreased in relative abundance. We further performed whole metagenomic shotgun sequencing (wMGS) and found increased ability of biofilm synthesis and the ability to sense external stimuli in PBDS based on functional annotation of mapped reads. From genome-resolved analysis of the samples, we identified 36 high-quality draft bacterial genome sequences with completion ≥70% and contamination ≤10%. Most of these genomes were classified into Proteobacteria, Firmicutes, or Actinobacteria.ConclusionsOur findings indicated that there is a subtle impact on biliary microbiome from cholelithiasis while the difference is more pronounced between the PBDS and SBDS. It was revealed that the diversity of biliary microbiota in PBDS is lower, while some metabolic pathways are up-regulated, including those linked to higher incidence of different types of cancer, providing new insights for the understanding of cholelithiasis with different origin.

Background: The relationship between non-alcoholic fatty liver disease (NAFLD) and cholelithiasis is intricate, with alterations in the microenvironment potentially mediating this interplay. Thus, this study aimed to explore the biliary microbiota and metabolites of patients with cholelithiasis and detect changes induced by comorbid NAFLD., Methods: In this study, 16S rRNA gene sequencing and metabolome analysis were performed on biliary samples collected from 35 subjects. Then, patients were stratified into two groups: the comorbidity group (n = 18), consisting of cholelithiasis patients with NAFLD, and the non-comorbidity group (n = 17), comprising cholelithiasis patients without NAFLD., Results: Comorbid NAFLD did not significantly increase α-diversity but affected β-diversity. A statistically significant difference was observed in the abundance of biliary metabolites between the two groups. Specifically, differences in the abundance of 4 phyla, 19 genera, and 28 metabolites were significant between the two groups. Correlation analysis demonstrated positive associations among 12α-hydroxylated bile acid levels, Pyramidobacter and Fusobacterium abundance, AST levels, and the fibrosis-4 index (p < 0.05, r > 0.3), all of which were increased in patients with cholelithiasis and comorbid NAFLD., Conclusions: The relationship between cholelithiasis and NAFLD influences the biliary microbial and metabolic profile, creating a detrimental microenvironment that promotes the disease progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

BackgroundThe pathogenesis of choledocholithiasis is closely related to the role of bacteria. However, little is known about the predictive role of bile bacteria in clinical conditions of patients and the compositional and functional characteristics of biliary microbiota in choledocholithiasis.MethodsTo investigate the predictive value of biliary bacteria, clinical data of 488 patients with choledocholithiasis were collected. The predictive value of common bile bacteria to patients’ clinical conditions was analyzed by logistic regression. Samples of bile and corresponding duodenal juice from 10 selected patients with choledocholithiasis were obtained, and the composition and function of microbial communities were analyzed based on 16S rRNA sequencing and Tax4Fun.ResultsThe clinical conditions of patients with choledocholithiasis, such as recurrence, the severity of acute cholangitis, and duration of hospital stay were closely related to different species of bile bacteria as well as antimicrobial-resistant bacteria. Employing 16S rRNA sequencing, the dominant phyla of biliary and duodenal microbiota were Proteobacteria and Firmicutes. The top three core microbiota at the genus level were Escherichia–Shigella, Fusobacterium, and Enterococcus. Escherichia coli accounted for the most abundant annotated species in both. Differences in composition between biliary and duodenal microbiota were not significant according to the alpha and beta diversities. Differential abundant features were not found in biliary microbiota indicated by A linear discriminant analysis effective size algorithm. The major pathways identified in biliary and duodenal microbiota were related to membrane transport, translation, replication and repair, carbohydrate and amino acid metabolism. However, no significant difference in those major pathways, as well as antimicrobial-resistance patterns, was observed between biliary and duodenal microbiota.ConclusionOur study first demonstrates the predictive contribution of biliary bacteria to the clinical conditions of patients with choledocholithiasis, and then it offers new insights into the compositional and functional features of biliary and duodenal microbiota. Similarities between biliary and duodenal microbiota support the theory of bacterial duodenal–biliary reflux in patients with choledocholithiasis. Meanwhile, when it is impracticable to obtain a bile sample, duodenal juice may be used as an alternative for bacterial culture and susceptibility tests.

Background: The pathogenesis of choledocholithiasis is closely related to the role of bacteria. However, little is known about the predictive role of bile bacteria in clinical conditions of patients and the compositional and functional characteristics of biliary microbiota in choledocholithiasis. Methods: To investigate the predictive value of biliary bacteria, clinical data of 488 patients with choledocholithiasis were collected. The predictive value of common bile bacteria to patients' clinical conditions was analyzed by logistic regression. Samples of bile and corresponding duodenal juice from 10 selected patients with choledocholithiasis were obtained, and the composition and function of microbial communities were analyzed based on 16S rRNA sequencing and Tax4Fun. Results: The clinical conditions of patients with choledocholithiasis, such as recurrence, the severity of acute cholangitis, and duration of hospital stay were closely related to different species of bile bacteria as well as antimicrobial-resistant bacteria. Employing 16S rRNA sequencing, the dominant phyla of biliary and duodenal microbiota were Proteobacteria and Firmicutes. The top three core microbiota at the genus level were Escherichia–Shigella, Fusobacterium , and Enterococcus. Escherichia coli accounted for the most abundant annotated species in both. Differences in composition between biliary and duodenal microbiota were not significant according to the alpha and beta diversities. Differential abundant features were not found in biliary microbiota indicated by A linear discriminant analysis effective size algorithm. The major pathways identified in biliary and duodenal microbiota were related to membrane transport, translation, replication and repair, carbohydrate and amino acid metabolism. However, no significant difference in those major pathways, as well as antimicrobial-resistance patterns, was observed between biliary and duodenal microbiota. Conclusion: Our study first demonstrates the predictive contribution of biliary bacteria to the clinical conditions of patients with choledocholithiasis, and then it offers new insights into the compositional and functional features of biliary and duodenal microbiota. Similarities between biliary and duodenal microbiota support the theory of bacterial duodenal–biliary reflux in patients with choledocholithiasis. Meanwhile, when it is impracticable to obtain a bile sample, duodenal juice may be used as an alternative for bacterial culture and susceptibility tests. [ABSTRACT FROM AUTHOR]

Summary: Natural killer T (NKT) cells are an abundant subset of liver lymphocytes activated by lipid antigens presented on CD1d molecules that are expressed by cholangiocytes. We aimed to determine if bile from patients with chronic liver diseases contains antigenic lipids that can activate NKT cells. Using murine invariant (24.7, 24.8 and DN32.D3) and non‐invariant (14S.6, 14S.7 and 14S.10) NKT hybridomas we investigated the presence of lipid antigens in bile collected from the gallbladder of patients undergoing liver transplantation due to end‐stage liver disease. Biliary microbiota profiles were generated using 16S rRNA amplicon sequencing. We found that the patient bile samples contain antigens that activate both invariant and non‐invariant NKT hybridomas (24.7, 24.8, DN32.D3, 14S.6, 14S.7 and 14S.10), as demonstrated by activation of at least one hybridoma by eight of 10 bile samples. Activation at high dilutions suggests that some antigens are highly potent. We used the non‐invariant NKT hybridoma 14S.6 to screen 21 additional patient bile samples for NKT‐reactivity and demonstrated that 12 of 21 bile samples resulted in activation, three of which gave a strong activation. Four of 12 activating bile samples contained microbial DNA. Our results reveal an immunological pathway that could be of critical importance in biliary immunology. [ABSTRACT FROM AUTHOR]

The biliary microbiota is related to the pathogenesis of human bile duct stones. However, the extent to which a history of invasive endoscopic sphincterotomy (EST) affects the biliary bacterial community remains largely unknown. We collected bile samples from the common bile duct of 100 choledocholithiasis patients. We performed 16S rRNA sequencing to investigate and compare the biliary microbial community. The patients without antibiotic treatment (AT) were grouped into three clusters based on their biliary microbial compositions. The patients with a history of EST were significantly enriched in one cluster mainly consisting of gastrointestinal bacteria compared with the other two clusters consisting of oral and environmental bacteria. The β-diversities of patients with and without EST were also significantly different, whereas the α-diversities were comparable. The only significantly enriched bacterial genus associated with a history of EST was Pyramidobacter, while eight other genera were significantly decreased. For patients with AT, seven of these genera maintained their association with EST, including Pyramidobacter. However, after AT, the difference in β-diversities was diminished. EST induced a marked shift in the biliary microbial composition. A cluster of biliary bacteria was associated with a history of EST, and Pyramidobacter was specific to EST.

The biliary microbiota is related to the pathogenesis of human bile duct stones. However, the extent to which a history of invasive endoscopic sphincterotomy (EST) affects the biliary bacterial community remains largely unknown. We collected bile samples from the common bile duct of 100 choledocholithiasis patients. We performed 16S rRNA sequencing to investigate and compare the biliary microbial community. The patients without antibiotic treatment (AT) were grouped into three clusters based on their biliary microbial compositions. The patients with a history of EST were significantly enriched in one cluster mainly consisting of gastrointestinal bacteria compared with the other two clusters consisting of oral and environmental bacteria. The β-diversities of patients with and without EST were also significantly different, whereas the α-diversities were comparable. The only significantly enriched bacterial genus associated with a history of EST was Pyramidobacter , while eight other genera were significantly decreased. For patients with AT, seven of these genera maintained their association with EST, including Pyramidobacter. However, after AT, the difference in β-diversities was diminished. EST induced a marked shift in the biliary microbial composition. A cluster of biliary bacteria was associated with a history of EST, and Pyramidobacter was specific to EST. [ABSTRACT FROM AUTHOR]

The microbiome plays a crucial role in maintaining the homeostasis of the organism. Recent evidence has provided novel insights for understanding the interaction between the microbiota and the host. However, the vast majority of such studies have analyzed the interactions taking place in the intestinal tract. The biliary tree has traditionally been considered sterile under normal conditions. However, the advent of metagenomic techniques has revealed an unexpectedly rich bacterial community in the biliary tract. Associations between specific microbiological patterns and inflammatory biliary diseases and cancer have been recently described. Hence, biliary dysbiosis may be a primary trigger in the pathogenesis of biliary diseases. In particular, recent studies have suggested that microorganisms could play a significant role in the development of gallstones, pathogenesis of autoimmune cholangiopathies and biliary carcinogenesis. Moreover, the intimate connection between the biliary tract, liver and pancreas, could reveal hidden influences on the development of diseases of these organs. Further studies are needed to deepen the comprehension of the influence of the biliary microbiota in human pathology. This knowledge could lead to the formulation of strategies for modulating the biliary microbiota in order to treat and prevent these pathological conditions. [ABSTRACT FROM AUTHOR]

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Background: Clonorchis sinensis ( C. sinensis) is a epidemiologically significant food-borne parasite, causing several hepatobiliary diseases. Biliary microbiota community structure might be influenced by infection with pathogens. However, the biliary microbiome of biliary obstruction patients infected with C. sinensis is still an unexplored aspect., Methods: A total of 50 biliary obstruction patients were enrolled, including 24 infected with C. sinensis and 26 non-infected subjects. The bile samples were collected by Endoscopic Retrograde Cholangiopancretography. Biliary microbiota alteration was analyzed through high-throughput 16S ribosomal RNA (rRNA) gene sequencing., Results: Our findings revealed that there was significant increase in both richness and diversity, as well as changes in the taxonomic composition of the biliary microbiota of C. sinensis infected patients. At the phylum level, C. sinensis infection induced Proteobacteria increased and Firmicutes reduced. At the genus level, the relative abundance of Pseudomonas and Staphylococcus increased significantly, while Enterococcus decreased prominently in infected groups ( P < 0.05). The PICRUSt analysis further showed remarkably different metabolic pathways between the two groups., Conclusion: C. sinensis infection could modify the biliary microbiota, increasing the abundance and changing the phylogenetic composition of bacterial in biliary obstruction patients. This study may help deepen the understanding of the host-biliary microbiota interplay with C. sinensis infection on the background of biliary obstruction and provide new insights into understanding the pathogenesis of clonorchiasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Li, Ding, Wan, Zhang, Jiang, Duan, Hu, Gao, Sun, Lu, Wang, Cheng, Zhang and Han.)

Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation of the biliary mucosa. Bile ducts in PSC are often colonized with bacteria. Although accumulating evidence demonstrates the importance of microbiota for mucosal immunity, little is known about the impact of bile duct colonization with bacteria on the clinical course of PSC. Bile samples were sent to culture during endoscopic retrograde cholangio-pancreatography before the administration of peri-interventional antibiotics. Procedures during overt bacterial cholangitis or with prior antibiotic treatment were excluded. The primary endpoint was defined as a composite clinical endpoint of decompensated cirrhosis and/or liver transplantation or death. A cohort of 189 patients with 591 bile fluid cultures was included. In multivariable Cox regression analysis, the presence of Enterococci (present in 28% of the patients), but not of other bacterial species, conferred risk of disease progression with a hazard ratio of 3.61 (95% confidence interval, 1.6–8.11; P =.002) to reach the composite clinical endpoint. Fungobilia, present in 19.6% of patients, was confirmed to associate with disease progression with a hazard ratio of 3.25 (95% confidence interval, 1.87–5.66; P <.001) to reach the composite clinical endpoint. The novel association of biliary colonization by Enterococci with disease progression underlines the importance of microbiota-mucosal interplay for the pathogenesis of PSC. These results should stimulate further mechanistic studies on the role of microbiota in PSC and highlight potential new therapeutic targets for a disease without effective treatment options. ▪ [ABSTRACT FROM AUTHOR]

Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies. However, little attention has been paid to the influence of diet on microbiotas, other than the gut microbiota. This is important in cholelithiasis, given that changes in the production of bile acids may affect gallbladder microbial communities. Our aim was to assess the association between regular dietary intake and gallbladder microbial composition. Fourteen adults with cholelithiasis and 14 controls, sex‒age-matched and without gastrointestinal pathology, were included. Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis. The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds. Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella. These results support a link between diet, biliary microbiota, and cholelithiasis. [ABSTRACT FROM AUTHOR]