Dataset Information

Gut Microbiota Composition of Biliary Atresia Patients Prior to Kasai Portoenterostomy Associates With Long-Term Outcome.

ABSTRACT:

Background and aims

Biliary atresia (BA) is a cholestatic, fibro-obliterative cholangiopathy of unknown etiology. BA is primarily treated by a surgical approach, i.e. the Kasai portoenterostomy (KPE), to obtain clearance of jaundice (COJ). The gut microbiota (GM) composition has been associated with the course of several cholestatic liver diseases. It is largely unknown, however, whether GM composition associates with the outcome of KPE. We compared the GM composition of BA patients and controls and assessed if GM composition before KPE was related to COJ after KPE.

Methods

We compared feces of term born BA patients before KPE and controls (patients undergoing inguinal hernia repair) by 16S rRNA sequencing. Composition and alpha diversity of the GM were compared between BA and controls before KPE and after KPE, between patients with COJ vs. without COJ (total serum bilirubin < or ≥ 20 μmol/L < 6mo post-KPE).

Results

Alpha diversity was comparable between BA (n = 12, age 1.6[1.3-1.8]mo) and controls (n = 6, age 2.0[1.4-2.1]mo; P = 0.22). Compared to controls, BA patients had lower abundances of Bifidobacteriaceae (β=-1.98, P < 0.001) and Lachnospiraceae (β=-1.84, P = 0.007), and higher abundances of Streptococcus (β=1.13, P = 0.003). The alpha diversity prior to KPE correlated negatively with COJ (R = -0.63, P = 0.03). Lower alpha diversity pre-KPE was associated with COJ [+] (βlogit = -0.64, P = 0.04). We observed greater abundances of genus Acinetobacter (β=1.27, P = 0.03) and family Clostridiaceae (β=1.45, P = 0.03) and lower abundances of the family Enterobacteriaceae, (genera Klebsiella (β=-1.21, P = 0.01), Salmonella (β=-1.57, P = 0.02)) in COJ [+] vs. COJ [-].

Conclusions

The gut microbiota of biliary atresia patients prior to Kasai portoenterostomy associates with outcome, clearance of jaundice, suggestive of predictive and mechanistic roles of the gut microbiota composition in bile homeostasis.

SUBMITTER: van Wessel DBE

PROVIDER: S-EPMC8448407 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and Aims: Biliary atresia (BA) is the most common cholestatic liver disease in neonates. Although the Kasai procedure can improve temporary biliary drainage in some cases, complications and liver fibrosis still develop. Liver transplantation is the ultimate treatment. The current study aimed to investigate the effect of previous Kasai surgery on gut microbiota and bile acid in BA with end-stage liver disease. Methods: Patients with BA with end-stage liver disease were divided into two groups according to whether they had previously undergone Kasai surgery (non-Kasai: n = 8, post-Kasai: n = 8). Metagenomic sequencing and ultraperformance liquid chromatography/tandem mass spectrometry were performed to identify the gut microbiota and bile acid. Results: Previous Kasai surgery had some effects on gut microbiota and bile acid in BA with end-stage liver disease. In the gut microbiome, the differential species were mainly distributed at the species level. Veillonella atypica had a significant increase in the non-Kasai group (P < 0.05). Bacteroides spp., Prevotella spp., Barnesiella spp., Parabacteroides spp., Heliobacterium spp., Erysipelatoclostridium spp. and Diaporthe spp. were increased in the post-Kasai group (P < 0.05). Concerning functional profiles, methionine biosynthesis was enriched in the non-Kasai group, while pyridoxal biosynthesis and riboflavin biosynthesis were enriched in the post-Kasai group (linear discriminant analysis > 2, P < 0.05). In stools, 17 bile acids were distinctly elevated in the post-Kasai group, such as cholic acid, chenodeoxycholic acid, β-muricholic acid and tauro α-muricholate (P < 0.05). Spearman correlation test showed that V. atypica had an enormously positive correlation with liver enzymes. Faecalibacterium prausnitzii and Escherichia coli were associated with derivatives of the alternative pathway of bile acid metabolism. Conclusion: Previous Kasai surgery can improve the gut microbiota and bile acid in patients with BA with end-stage liver disease. This improvement contributes to maintaining the intestinal barrier.

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