Gut Microbiota Dysbiosis Associated with Bile Acid Metabolism in Neonatal Cholestasis Disease

Meng Li,Meng Li,Mingying Wang,Hongwei Hu,Hongwei Hu,Chuanfa Liu,Chuanfa Liu,Chuanfa Liu,Mingying Wang,Yongkun Huang,Sixiang Liu,Jianwen Yin,Sixiang Liu

doi:10.1038/s41598-020-64728-4

Abstract

Neonatal cholestasis disease (NCD) is a complex and easily mis-diagnosed condition. We analyzed microbiota community structure in feces and measured short-chain fatty acids, bile acids (BAs) and liver function of 12 healthy, 13 NCD, and 13 treated infants after diagnosis. Based on 16S rRNA gene amplicon sequencing and gas-chromatographic-mass-spectrometric analysis of secondary BAs, we identified microbial genera and metabolites that associate with abnormal bile secretion. Streptococcus gallolyticus and Parabacteroides distasonis, and Lactobacillus gasseri had higher relative abundance in healthy and NCD infants respectively. Compared to NCD patients, healthy infants had higher LCA, CDCA and GCDCA fecal concentrations. The three microbial species and three secondary bile acids were selected as potential non-invasive combined biomarkers to diagnose NCD. We propose that microbiota-metabolite combined biomarkers could be used for diagnosis of NCD, and this may contribute to improved early clinical diagnosis of NCD in the future.

Highlights

Among the most studied causes of Neonatal cholestasis disease (NCD) in recent years are metabolic diseases and disorders of bile transport and bile acids (BAs) synthesis
To discover metabolic features associated with occurrence of neonatal cholestasis, we measured fecal BAs in all four groups and liver function in NNC, TNCR, and TNCN groups (Fig. 1 and additional File 1)
BAs in stool, including glycochenodeoxycholic acid (GCDCA) (P = 0.049), chenodeoxycholic acid (CDCA) (P = 0.025), CA (P = 0.019) and lithocholic acid (LCA) (P = 0.007), showed significantly higher concentrations in the healthy controls (HC) group compared to the NNC group (Fig. 1)

Summary

Introduction

Among the most studied causes of NCD in recent years are metabolic diseases and disorders of bile transport and BA synthesis. A study by Guo et al (2018) revealed altered gut microbial composition and co-occurrence of certain species in cholestatic infants compared with healthy infants[22], indicating a metabolic disorder modulated by gut microbiota associated with occurrence of cholestatic jaundice. Zhou et al (2019) reported an alteration of gut microbiota in neonatal cholestasis patients, mainly manifested as a significant increase in species richness and an increased abundance of potentially pathogenic species. Combined with analysis of metabolites in both serum and feces, it should be feasible to develop gut microbial markers that improve the diagnosis of cholestatic liver disease in infants. Fecal samples were obtained from all subjects for 16S rRNA-based gut microbe analysis as well as quantitative measurements of both short-chain fatty acids (SCFAs) and BAs. Serum samples from all patients were used to measure the change of common liver function indexes before and after treatment (additional file 6). Our aim was to identify gut microbial markers co-occurring with specific metabolites associated with neonatal cholestasis

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Conclusion