Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen Escherichia coli that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids.
AbstractThis study aimed to investigate the mechanism of mangiferin on regulating endoplasmic reticulum (ER) stress in acute liver injury. The mouse model of acute liver injury was established by injection of LPS/D-GalN. The primary mouse hepatocytes were stimulated with LPS to induce the in vitro model. The effect of miR-20a/101a on the luciferase activity of Nrf2 3′-UTR was assessed by luciferase reporter assay. Mangiferin improved the liver function, inhibited the oxidative stress and ER stress and down-regulated the expressions of miR-20a and miR-101a in LPS/D-GalN-induced mice and LPS-induced hepatocytes. The knockdown of miR-20a and miR-101a co-operatively alleviated ER stress of LPS-induced hepatocytes. miR-20a and miR-101a both targeted Nrf2 and the over-expression of miR-20a or miR-101a decreased Nrf2 protein level, while their silences increased Nrf2 protein level. The silence of miR-20a and miR-101a promoted Nrf2 expression and inhibited the ER stress in LPS-induced hepatocytes, while the knockdown of Nrf2 reversed these effects. The over-expression of miR-20a and miR-101a eliminated the effects of mangiferin on Nrf2 protein level and ER stress in LPS-induced hepatocytes and Nrf2 over-expression altered these trends. Our findings suggest that mangiferin alleviates ER stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis.
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