Background Evidence supports an association between cholestatic liver disease and changes in microbiome composition. Nevertheless, the identification of this special type of biliary atresia from non-biliary atresia cholestasis is still a major clinical difficulty. The purpose of this study is to compare the differences in the composition of gut microbiome between infants with biliary atresia and infant with non-biliary atrestic cholestasis, to find new ways to identify and diagnose these two diseases early, to understand the influence of the presence or absence of bile on the composition of the gut microbiome in infants with cholestasis. Methods Using 16S rDNA gene sequencing technology to analyze the intestinal flora of the participants. Results In terms of diversity, there is an obvious structural separation in the intestinal microbiota of the BA group and the CD group, and this structural separation also exists in the comparison between the two groups before surgery. Taxonomic analysis demonstrated that the two groups showed an increase in Proteobacteria and Firmicutes before surgery, and the relative abundance of potential pathogens such as Shigella, Streptococcus, Klebsiella, etc. increased, potential probiotics such as Bifidobacteria and Lactobacillus decreased, but the relative abundance of each genus was different between groups. It was found that Enterococcus, Ralstonia, Nitriliruptoraceae, etc. were differentially enriched in the BA group, the CD group are mainly enriched in Veillonella, Clostridium_sensu_stricto_1 and Lactobacillus. Functional analysis of the groups showed that the BA group mainly focused on the processes of energy release processes, and the CD group mainly focused on the biosynthesis of amino-acids to consume energy. Conclusions The composition of intestinal flora is different between biliary atresia and non-biliary atretic cholestasis. Enterococcus, Ralstonia, etc. may become biomarkers for the identification and diagnosis of both.
Background: The farnesoid X receptor (FXR) is a key factor regulating hepatic bile acid synthesis and enterohepatic circulation. Repression of bile acid synthesis by the FXR is a potential strategy for treating cholestatic liver disease. However, the role of intestinal FXR on the intestinal barrier and intestinal microbiota needs further investigation.Materials: Intestinal tissues were collected from patients with biliary atresia or without hepatobiliary disease. Then, intestinal mRNA levels of FXR-related molecules were determined. To investigate the effect of FXR activation, bile-duct-ligation rats were treated with obeticholic acid [OCA (5 mg/kg/day)] or vehicle (0.5% methyl cellulose) per oral gavage for 14 days. The mRNA levels of intestinal FXR, SHP, TNF-α, FGF15 and bile acid transporter levels were determined. In addition, the intestinal permeability, morphologic changes, and composition of the intestinal microbiota were evaluated. Gut Microbiome was determined by 16S rDNA MiSeq sequencing, and functional profiling of microbial communities was predicted with BugBase and PICRUSt2. Finally, the role of OCA in injured intestinal epithelial cell apoptosis and proliferation was examined by pretreatment with lipopolysaccharide (LPS) in Caco-2 cells.Results: The downstream of the FXR in ileum tissues was inhibited in biliary obstruction. Activation of the FXR signaling pathway by OCA significantly reduced liver fibrosis and intestinal inflammation, improved intestinal microbiota, and protected intestinal mucosa in BDL rats. OCA also altered the functional capacities of ileum microbiota in BDL rats. Significant differences existed between the controls and BDL rats, which were attenuated by OCA in the alpha diversity analysis. Principal coordinates analysis showed that microbial communities in BDL rats clustered separately from controls, and OCA treatment attenuated the distinction. Bugbase and PICRUSt2 analysis showed that OCA changed the composition and structure of the intestinal microbiota and improved the metabolic function of the intestinal microbiota by increasing the relative abundance of beneficial bacteria and reducing the relative abundance of harmful bacteria. Moreover, OCA reduced the apoptosis induced by LPS in Caco-2 cells.Conclusion: The FXR agonist, OCA, activates the intestinal FXR signaling pathway and improves the composition and structure of the intestinal microbiota and intestinal barrier in BDL rats.
Background Evidence supports an association between cholestatic liver disease and changes in microbiome composition. Nevertheless, the identification of this special type of biliary atresia from non-biliary atresia cholestasis is still a major clinical difficulty. The purpose of this study is to compare the differences in the composition of gut microbiome between infants with biliary atresia and infant with non-biliary atrestic cholestasis, to find new ways to identify and diagnose these two diseases early, to understand the influence of the presence or absence of bile on the composition of the gut microbiome in infants with cholestasis. Methods Using 16S rDNA gene sequencing technology to analyze the intestinal flora of the participants. Results In terms of diversity, there is an obvious structural separation in the intestinal microbiota of the BA group and the CD group, and this structural separation also exists in the comparison between the two groups before surgery. Species analysis demonstrated that the two groups showed an increase in Proteobacteria and Firmicutes before surgery, and the relative abundance of pathogens such as Shigella, Streptococcus, Klebsiella, etc. increased, probiotics such as Bifidobacteria and Lactobacillus decreased, but the relative abundance of each genus was different between groups. It was found that Enterococcus, Ralstonia, Nitriliruptoraceae, etc. were differentially enriched in the BA group, the CD group are mainly enriched in Veillonella, Clostridium_sensu_stricto_1 and Lactobacillus. Functional analysis of the groups showed that the BA group mainly focused on the processes of energy release processes, and the CD group mainly focused on the biosynthesis of amino-acids to consume energy. Conclusions The composition of intestinal flora is different between biliary atresia and non-biliary atretic cholestasis. Enterococcus, Ralstonia, etc. may become biomarkers for the identification and diagnosis of both.
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