The biliary microbiome in ischaemic‐type biliary lesions can be shaped by stenting but is resilient to antibiotic treatment

• Published in: Liver international 2022-05, Vol.42 (5), p.1070-1083
• Main Authors: Klein, Friederike, Wellhöner, Freya, Plumeier, Iris, Kahl, Silke, Chhatwal, Patrick, Vital, Marius, Voigtländer, Torsten, Pieper, Dietmar H., Manns, Michael P., Lenzen, Henrike, Solbach, Philipp, Heidrich, Benjamin
• Format: Article
• Language: English
• Subjects: 16S; anastomotic strictures; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antiinfectives and antibacterials; bacterial cholangitis; biliary stenting; Biliary Tract; Community structure; Humans; Ischemia; ITBL; Lesions; Liver; Liver transplantation; Metabolites; Metagenomics; Microbiomes; Microbiota; Microorganisms; Multivariate analysis; Patients; RNA, Ribosomal, 16S; rRNA 16S; Transplantation
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.15194

This study aims to characterize the biliary microbiome as neglected factor in patients with ischaemic‐type biliary lesions (ITBL) after liver transplantation. Therefore, the V1–V2 region of the 16S rRNA gene was sequenced in 175 bile samples. Samples from patients with anastomotic strictures (AS) served as controls. Multivariate analysis and in silico metagenomics were applied cross‐sectionally and longitudinally. The microbial community differed significantly between ITBL and AS in terms of alpha and beta diversity. Both, antibiotic treatment and stenting were associated independently with differences in the microbial community structure. In contrast to AS, in ITBL stenting was associated with pronounced differences in the biliary microbiome, whereas no differences associated with antibiotic treatment could be observed in ITBL contrasting the pronounced differences found in AS. Bacterial pathways involved in the production of antibacterial metabolites were increased in ITBL with antibiotic treatment. After liver transplantation, the biliary tract harbours a complex microbial community with significant differences between ITBL and AS. Fundamental changes in the microbial community in ITBL can be achieved with biliary stenting. However, the effect of antibiotic treatment in ITBL was minimal. Therefore, antibiotics should be administered wisely in order to reduce emerging resistance of the biliary microbiome towards external antibiotics. Lay Summary Ischaemic‐type biliary lesions (ITBL) and anastomotic strictures (AS) are complications after liver transplantation that are similar in their clinical presentation but differ in the course of the disease. The biliary microbiome shows distinct differences in ITBL compared to AS. By biliary stenting, the microbial community can be shaped in ITBL more pronounced than in AS, whereas it is vice versa under administration of antibiotic medication. In ITBL, the biliary microbial community seems to be particularly resilient to external antibiotic substances owing to protection by biofilm formation and self‐production of antimicrobial secondary metabolites.