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The Fecal Microbiome in Infants with Biliary Atresia Associates with Bile Flow after Kasai Portoenterostomy.

BACKGROUND
Biliary atresia's (BA) response to surgical Kasai portoenterostomy (KP) is uneven and dependent upon bile flow; 50% of infants require a liver transplant by 24 months. We hypothesized that the microbiome may identify and associate with outcomes in BA.


METHODS
Stool samples were collected from infants with cholestasis (n = 15), 8 of which with BA were followed longitudinally.16S sequencing was performed on all samples (n = 45). Whole Genome Sequencing (WGS) was performed on BA pre-KP samples (n = 8). Infants with BA, other forms of cholestasis, BA infants with very good bile flow (VGBF) and not (nVGBF), (VGBF dichotomized by TSBA <40 μmol/L by 6 months) were compared.


RESULTS
Of the 8 infants with BA, 4 infants had VGBF. Microbial richness was inversely proportional to degree of cholestasis (p = 0.046). Increased Bifidobacterium abundance associated with VGBF (p = 0.03) and decreased cholestasis (p < 0.01) at 1 month post-KP. Pre-KP, community structure differed in infants with BA vs other cholestasis. Interestingly, infants who subsequently achieved VGBF had increased diversity (p = 0.03) and different community structure at the pre-KP time point. WGS corroborated Bifidobacterium's pre-KP importance.


CONCLUSIONS
The microbiome differs between infants with BA and other cholestasis. It additionally differs between infants with BA who have good and poor bile flow, and thus outcomes, post-KP. These differences are seen even before KP. These data suggest that bile influences the development of the infant microbiome and that there may be possible influences of the pre-and post-KP microbiome on bile flow after KP. Further larger studies are needed to confirm these findings.