The influence of liver transplantation on the interplay between gut microbiome and bile acid homeostasis in children with biliary atresia

Medientyp: E-Artikel
Titel: The influence of liver transplantation on the interplay between gut microbiome and bile acid homeostasis in children with biliary atresia
Beteiligte: Waldner, Birgit; Aldrian, Denise; Zöggeler, Thomas; Oberacher, Herbert; Oberhuber, Rupert; Schneeberger, Stefan; Messner, Franka; Schneider, Anna M.; Kohlmaier, Benno; Lanzersdorfer, Roland; Huber, Wolf-Dietrich; Entenmann, Andreas; Müller, Thomas; Vogel, Georg F.
Erschienen: Ovid Technologies (Wolters Kluwer Health), 2023
Erschienen in: Hepatology Communications
Sprache: Englisch
DOI: 10.1097/hc9.0000000000000151
ISSN: 2471-254X
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Beschreibung: <jats:sec> <jats:title>Background:</jats:title> <jats:p>Biliary atresia (BA) causes neonatal cholestasis and rapidly progresses into cirrhosis if left untreated. Kasai portoenterostomy may delay cirrhosis. BA remains among the most common indications for liver transplantation (LT) during childhood. Liver function and gut microbiome are interconnected. Disturbed liver function and enterohepatic signaling influence microbial diversity. We, herein, investigate the impact of LT and reestablishment of bile flow on gut microbiome–bile acid homeostasis in children with BA before (pre, n = 10), 3 months (post3m, n = 12), 12 months (post12m, n = 9), and more than 24 months (post24 + m, n = 12) after LT.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>We analyzed the intestinal microbiome of BA patients before and after LT by 16S-rRNA-sequencing and bioinformatics analyses, and serum primary and secondary bile acid levels.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>The gut microbiome in BA patients exhibits a markedly reduced alpha diversity in pre (<jats:italic toggle="yes">p</jats:italic> = 0.015) and post3m group (<jats:italic toggle="yes">p</jats:italic> = 0.044), and approximated healthy control groups at later timepoints post12m (<jats:italic toggle="yes">p</jats:italic> = 1.0) and post24 + m (<jats:italic toggle="yes">p</jats:italic> = 0.74). Beta diversity analysis showed overall community structure similarities of pre and post3m (<jats:italic toggle="yes">p</jats:italic> = 0.675), but both differed from the post24 + m (<jats:italic toggle="yes">p</jats:italic> < 0.001). Longitudinal analysis of the composition of the gut microbiome revealed the <jats:italic toggle="yes">Klebsiella</jats:italic> genus to show increased abundance in the post24 + m group compared with an age-matched control (<jats:italic toggle="yes">p</jats:italic> = 0.029). Secondary bile acid production increased 2+ years after LT (<jats:italic toggle="yes">p</jats:italic> = 0.03). Multivariable associations of microbial communities and clinical metadata reveal several significant associations of microbial genera with tacrolimus and mycophenolate mofetil–based immunosuppressive regimens.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>In children with BA, the gut microbiome shows strongly reduced diversity before and shortly after LT, and approximates healthy controls at later timepoints. Changes in diversity correlate with altered secondary bile acid synthesis at 2+ years and with the selection of different immunosuppressants.</jats:p> </jats:sec>
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