Bile acid and microbiome interactions in the developing child

Abstract

Interactions between the gut microbiome and bile acids are complex and are linked to outcomes in pediatric liver disease by mechanisms that are incompletely understood. In adults, primary bile acids are synthesized in the liver and secreted into the intestine, where complex communities of gut microbes deconjugate, oxidize, epimerize, and 7α-dehydroxylate bile acids into a diverse array of unconjugated, secondary, allo-, iso-, and oxo-bile acids. In contrast, the infant gut microbiota contains a simple, Bifidobacterium-dominant community that transitions to a more diverse, adult-like community as additional microbes colonize the gut. This microbial succession gradually confers deconjugation, oxidation, epimerization, and 7α-dehydroxylation activities that mature the bile acid pool from a profile dominated by primary bile acids early in life to a more diverse, adult-like bile acid profile in later childhood. Altered bile acid profiles in pediatric cholestatic disorders have the potential to change the developmental trajectory of the microbiome. Conversely, alterations in the gut microbiome may re-shape the bile acid pool and hepatic bile acid metabolism. Understanding the mechanisms underlying these interactions will increase our understanding of liver pathophysiology and will motivate new therapeutic strategies for pediatric hepatic disorders. This review aims to highlight differences between the pediatric and adult intestinal microbiome and bile acid pool, and to discuss interactions between gut microbes and bile acids that are critical in early life and that may impact outcomes in infants and children with cholestatic liver disease, including biliary atresia.

Keywords: biliary atresia; cholestasis; enterohepatic circulation; infant.