AUTHOR=Song Wei , Sun Li-Ying , Zhu Zhi-Jun , Wei Lin , Qu Wei , Zeng Zhi-Gui , Liu Ying , Zhang Hai-Ming , Guo Wei 

TITLE=Association of Gut Microbiota and Metabolites With Disease Progression in Children With Biliary Atresia

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.698900

DOI=10.3389/fimmu.2021.698900

ISSN=1664-3224

ABSTRACT=<sec><title>Background and Aims</title><p>Biliary atresia is the most common cause of liver disease and liver transplantation in children. The accumulation of bile acids in hepatocytes and the stimulation of the intestinal microbiome can aggravate the disease progression. This study investigated changes in the composition of the gut microbiota and its metabolites in biliary atresia and the possible effects of these changes on disease progression.</p></sec><sec><title>Methods</title><p>Stool samples of biliary atresia at different disease stages and matched control individuals were collected (early stage: 16 patients, 16 controls; later stage: 16 patients, 10 controls). Metagenomic sequencing was performed to evaluate the gut microbiota structure. Untargeted metabolomics was performed to detect and analyze the metabolites and bile acid composition.</p></sec><sec><title>Results</title><p>A disturbed gut microbiota structure occurred in the early and later stages of biliary atresia. <italic>Klebsiella</italic>, <italic>Streptococcus</italic>, <italic>Veillonella</italic>, and <italic>Enterococcus</italic> have always been dominant. The abundance of <italic>V. atypica</italic> displayed significant changes between the early and later stages of biliary atresia. Combined with clinical indicators, Spearman’s analysis showed that <italic>Klebsiella</italic> and <italic>Veillonella atypica</italic> strongly correlated with liver enzymes. <italic>Enterococcus faecium</italic> had an enormously positive relationship with lithocholic acid derivatives. Metabolites involved in tryptophan metabolism were changed in the patients with biliary atresia, which had a significant association with stool <italic>V. atypica</italic> and blood total bilirubin (<italic>p</italic> &lt; 0.05).</p></sec><sec><title>Conclusions</title><p>The liver damage of biliary atresia was directly or indirectly exacerbated by the interaction of enriched <italic>Klebsiella</italic> (<italic>K. pneumoniae</italic>), <italic>Veillonella</italic> (<italic>V. atypica</italic>), and <italic>Enterococcus</italic> (<italic>E. faecium</italic>) with dysmetabolism of tryptophan and bile acid.</p></sec>