Disease-Associated Gut Microbiota Reduces the Profile of Secondary Bile Acids in Pediatric Nonalcoholic Fatty Liver Disease.

Jiake Yu,Qi Liu,Liya Chen,Yufei Ruan,Yiping Chen,Hu Zhang

doi:10.3389/fcimb.2021.698852

Abstract

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.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of obesity-related metabolic diseases
The gut microbiota deconjugate bile acids and convert primary bile acids, cholic acid (CA), and chenodeoxycholic acid (CDCA) into secondary bile acids, such as deoxycholic acid (DCA) and lithocholic acid (LCA), and it has a potent effect on bile acid signaling (Ridlon et al, 2006)
We detected gut microbiota dysbiosis in the feces of children with nonalcoholic fatty liver disease (NAFLD), which was characterized by an increase in the pathogenic species E. coli, E. cloacae, and K. pneumoniae, a decrease in potentially beneficial gut microbiota (A. muciniphila and A. putredinis), and lower abundances of the genera Bacteroides, Eubacterium and Ruminococcaceae, which are involved in bile acid metabolism (Song et al, 2019)

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the liver manifestation of obesity-related metabolic diseases. Microbiota Dysbiosis in Pediatric NAFLD chronic liver diseases in children worldwide and affects about 310% of children (Nobili et al, 2016). A recent metagenomic sequencing study revealed altered gut microbial composition and functional annotations in children with NAFLD at the fecal level, which were significantly different from that found in healthy children (Zhao et al, 2019). A recent 16S rRNA sequencing study showed that NAFLD was associated with altered gut microbiota and concentrations of serum bile acids, which contributed to impaired hepatic bile acid-mediated signaling in NAFLD livers (Jiao et al, 2018). To the best of our knowledge, the relationship between gut microbiota dysbiosis and bile acid composition in pediatric NAFLD remains to be elucidated

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