Association of gut microbiota and gut metabolites and adverse outcomes in biliary atresia: A longitudinal prospective study

Background: The Kasai portoenterostomy (KPE) aims to re-establish bile flow in biliary atresia (BA); however, BA remains the commonest indication for liver transplantation in pediatrics. Gut microbiota-host interplay is increasingly associated with outcomes in chronic liver disease. This study characterized fecal microbiota and fatty acid metabolites in BA.

Methods: Fecal samples were prospectively collected in newly diagnosed BA infants (n = 55) before and after KPE. Age-matched healthy control (n = 19) and cholestatic control (n = 21) fecal samples were collected. Fecal 16S rRNA gene amplicon sequencing for gut microbiota and gas chromatography for fecal fatty acids was performed.

Results: Increased abundance of Enterococcus in pre-KPE BA and cholestatic control infants, compared to healthy infants, was demonstrated. At the early post-KPE time points, increased alpha diversity was revealed in BA versus healthy cohorts. A lower relative abundance of Bifidobacterium and increased Enterococcus, Clostridium, Fusobacterium, and Pseudomonas was seen in infants with BA. Fecal acetate was reduced, and fecal butyrate and propionate were elevated in early post-KPE BA infants. Higher post-KPE alpha diversity was associated with nonfavorable clinical outcomes (6-month jaundice and liver transplantation). A higher relative abundance of post-KPE Streptococcus and Fusobacterium and a lower relative abundance of Dorea, Blautia, and Oscillospira were associated with nonfavorable clinical outcomes. Blautia inversely correlated to liver disease severity, and Bifidobacterium inversely correlated to fibrosis biomarkers. Bifidobacterium abundance was significantly lower in infants experiencing cholangitis within 6 months after KPE.

Conclusions: Increased diversity, enrichment of pathogenic, and depletion of beneficial microbiota early post-KPE are all factors associated with nonfavorable BA outcomes. Manipulation of gut microbiota in the early postsurgical period could provide therapeutic potential.