AUTHOR=Guo Cheng , Li Yinhu , Wang Peipei , Li Yingchao , Qiu Chuangzhao , Li Muxia , Wang Daxi , Zhao Ruiqin , Li Dongfang , Wang Ye , Li Shuaicheng , Dai Wenkui , Zhang Lin 

TITLE=Alterations of Gut Microbiota in Cholestatic Infants and Their Correlation With Hepatic Function

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02682

DOI=10.3389/fmicb.2018.02682

ISSN=1664-302X

ABSTRACT=<p>Cholestasis is a major hepatic disease in infants, with increasing morbidity in recent years. Accumulating evidence has revealed that the gut microbiota (GM) is associated with liver diseases, such as non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, GM alterations in cholestatic infants and the correlation between the GM and hepatic functions remain uninvestigated. In this study, 43 cholestatic infants (IC group) and 37 healthy infants (H group) were enrolled to detect GM discrepancies using 16S rDNA analysis. The diversity in the bacterial community was significantly lower in the IC group than that in the H group (<italic>P</italic> = 0.013). After determining the top 10 abundant genera of microbes in the IC and H groups, we found that 13 of them were differentially enriched, including <italic>Bifidobacterium, Bacteroides, Streptococcus, Enterococcus</italic>, and <italic>Staphylococcus</italic>. As compared with the H group, the IC group had a more complex GM co-occurrence network featured by three core nodes: <italic>Phyllobacterium, Ruminococcus</italic>, and <italic>Anaerostipes</italic>. In addition, the positive correlation between <italic>Faecalibacterium</italic> and <italic>Erysipelatoclostridium</italic> (<italic>r</italic> = 0.689, <italic>P</italic> = 0.000, FDR = 0.009) was not observed in the IC patients. Using the GM composition, the cholestatic patients can be distinguished from healthy infants with high accuracy [areas under receiver operating curve (AUC) &gt; 0.97], wherein <italic>Rothia, Eggerthella, Phyllobacterium</italic>, and <italic>Blautia</italic> are identified as valuable biomarkers. Using KEGG annotation, we identified 32 functional categories with significant difference in enrichment of the GM of IC patients, including IC-enriched functional categories that were related to lipid metabolism, biodegradation and metabolism of xenobiotics, and various diseases. In contrast, the number of functions associated with amino acid metabolism, nucleotide metabolism, and vitamins metabolism was reduced in the IC patients. We also identified significant correlation between GM composition and indicators of hepatic function. <italic>Megasphaera</italic> positively correlated with total bilirubin (<italic>r</italic> = 0.455, <italic>P</italic> = 0.002) and direct bilirubin (<italic>r</italic> = 0.441, <italic>P</italic> = 0.003), whereas γ-glutamyl transpeptidase was positively associated with <italic>Parasutterella</italic> (<italic>r</italic> = 0.466, <italic>P</italic> = 0.002) and negatively related to <italic>Streptococcus</italic> (<italic>r</italic> = -0.450, <italic>P</italic> = 0.003). This study describes the GM characteristics in the cholestatic infants, illustrates the association between the GM components and the hepatic function, and provides a solid theoretical basis for GM intervention for the treatment of infantile cholestasis.</p>