Background: Emerging evidence highlights the role of biliary microbiota in hepato-biliary-pancreatic diseases. The characteristics of biliary microbiota in malignant bile duct obstruction remain poorly understood. This study aims to investigate the composition and metabolic functions of biliary microbiota in patients with malignant obstruction. Methods: Eligible patients were enrolled in this prospective study at First Affiliated Hospital of Soochow University between December 2022 and October 2023, including distal cholangiocarcinoma, hilar cholangiocarcinoma, pancreatic ductal adenocarcinoma, periampullary carcinoma, and gallbladder carcinoma. The patients with choledocholithiasis served as controls. Bile samples were collected via endoscopic retrograde cholangiopancreatography. Microbiota identification was performed using 16S rRNA sequencing, while bile acids were analyzed using mass spectrometry. Results: A total of 56 patients were successfully enrolled in this study, 25 in the tumor group and 31 in the stone group. A distinct biliary microbial community was observed in patients with malignant bile duct obstruction, consisting of Prevotella, Uruburuella, Atopostipes, Clostridium IV, Halomonas, Tannerella, Porphyromonas, Achromobacter, Rouxiella, Campylobacter, Corynebacterium, Turicibacter, Muribaculum, Selenomonas, and Alloprevotella at genus level. Notably, Clostridium IV, Halomonas, Rouxiella, and Turicibacter were exclusively present in the tumor group. Bile acid levels were significantly lower in the tumor group (P < 0.05), except for ursodeoxycholic acid and taurocholic acid. Additionally, 22 metabolic pathways were enriched in the tumor group. Conclusions: This study elucidates the community and metabolic potential of biliary microbiota in malignant bile duct obstruction. The findings offer valuable insights for disease assessment and provide a foundation for further research into the role of biliary microbiota in malignancy.

Background/Objectives: The solute carrier family 26, member 2 (SLC26A2) gene, which belongs to the family of SLC26 transporters, can be detected in multiple tissues. However, the studies of SLC26A2 in colon-related diseases are still limited and incompletely understood, especially in ulcerative colitis (UC). Methods: In this study, we attempted to search and identify putative UC candidate genes within a large number of known genes by multiple bioinformatics analyses. The potential cellular characteristics and biological functions of SLC26A2 in the pathogenesis of UC were also elucidated. Results: Notably, SLC26A2 was representative and down-regulated in the intestinal mucosa of patients with active UC, compared to healthy controls. Decreased levels of SLC26A2 were proved to have a more value in diagnosis of UC patients, and closely correlated with some UC characteristics, including the Mayo score and Paediatric Ulcerative Colitis Activity Index (PUCAI). Mechanistically, subsequent results from published datasets and our validated clinical data all strongly implied that SLC26A2 was negatively correlated with the IL-17 signaling pathway, and positively associated with the tight junction, which led to abnormal immune cell infiltration and inflammatory injuries. After establishing the UC mice models in vivo by orally administration of DSS in portable water, SLC26A2 was significantly down-regulated at the mRNA or protein level, when compared to that in the control groups. Furthermore, the correlation analyses confirmed that SLC26A2 was positively associated with CLDN3, and negatively correlated with IL-17A expression in colon tissues. In addition, according to the SLC26A2 expression, UC patients were divided into different subgroups. The potential target drugs for UC treatment, such as progesterone, tetradioxin, and dexamethasone, were initially predicted and exerted anti-inflammatory effects via the common molecule-SLC26A2. Conclusions: SLC26A2 might be served as a protective candidate in the UC pathogenesis as well as a potential drug target for UC treatment.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is widely used in the treatment of choledocholithiasis, while successful extraction of common bile duct stone (CBDS) is commonly hampered by the number of stones. Biliary microbiota has a profound influence on the occurrence of CBDS. In this study, we aimed to investigate the characteristics and metabolic potential of biliary microbiota in patients with multiple CBDS. Methods: Eligible patients were prospectively enrolled in this study at First Affiliated Hospital of Soochow University between December 2022 and October 2023. Bile samples were collected through ERCP. The samples were tested for biliary microbiota and bile acids using 16S rRNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry, respectively. Metabolic functions were predicted by PICRUSt 2.0 calculation based on MetaCyc database. Results: A total of 31 patients were enrolled, including 17 in multiple stone (MS) group and 14 in single stone (SS) group. Distinct biliary microbial composition was identified in MS group, with a significantly higher abundance of Proteobacteria at phylum level and Enterococcus at genus level, respectively. Klebsiella, Aquabacterium, Morganella and Diaphorobacter were significantly abundant in MS group. Both Morganella and Aeromonas were exclusively found in MS group, along with the absence of Metaprevotella. Chenodeoxycholic acid was significantly enriched in MS group. It was negatively correlated with Enhydrobacter, Massilia and Neglecta that were abundant in SS group. Several metabolic pathways that could increase the risk of CBDS were also enriched in MS group, including L-methionine biosynthesis, aspartate superpathway, glucose and glucose-1-phosphate degradation and superpathway of glycolysis and the Entner-Doudoroff pathway. Conclusion: This study illustrated the microbial structure and metabolic potential of biliary flora in patients with multiple CBDS. The unique biliary microbial community holds the predictive value for clinical conditions. The findings provide new insights about biliary microbiota into the etiology of multiple CBDS.