Gut Microbiota Dysbiosis is Associated with Altered Bile Acid Metabolism in Infantile Cholestasis

ABSTRACT:

The co-occurrence of gut microbiota dysbiosis and bile acids (BAs) metabolism alteration has been reported in several human liver diseases. However, the gut microbiota dysbiosis in infantile cholestatic jaundice (CJ), and the linkage between gut bacterial changes and alterations of BAs metabolism are undetermined. To address this question, we performed 16S rRNA gene sequencing to determine the compositional and functional differences in gut microbiota, and access their association with fecal levels of primary and secondary BAs in infants with CJ. Our data revealed that CJ infants showed marked declines in fecal levels of primary BAs and most secondary BAs. A decreased ratio of cholic acid (CA):chenodeoxycholic acid (CDCA) in CJ indicated a shift in BA synthesis from the primary to the alternative BA pathway. The CJ-enriched bacterial taxa corresponds to genera Clostridium, Gemella, Streptococcus, Veillonella, and family Enterobacteriaceae were negatively correlated with fecal BAs level and the CDCA:CA ratio, but positively correlated with the serological indexes of liver functions. An increased ratio of deoxycholic acid (DCA):CA was observed in a proportion of CJ. The CJ-depleted bacteria, including Bifidobacterium and Faecalibacterium prausnitzii, were positively and negatively correlated with fecal levels of BAs and the serological markers of impaired liver function, respectively. In conclusion, the reduced concentration of BAs in the gut of CJ is correlated with gut microbiota dysbiosis. The altered gut microbiota of CJ is likely to upregulate the conversion from primary to secondary BAs.

Linked cross omic data sets:

Raw sequencing data associated with this study are available in the European Nucleotide Archive (ENA): accession number PRJEB33641.

INSTRUMENT(S): Liquid Chromatography MS - alternating - reverse phase

SUBMITTER: Xuefeng Gao 

PROVIDER: MTBLS1295 | MetaboLights | 2019-11-30

REPOSITORIES: MetaboLights