Abstract

The dysbiosis in gut microbiota could affect host metabolism and contribute to the development of nonalcoholic fatty liver disease (NAFLD). Da-Chai-Hu decoction (DCH) has demonstrated protective effects on NAFLD, however, the exact mechanisms remain unclear. In this study, we established a NAFLD rat model using a high fat diet (HFD) and provided treatment with DCH. The changes in gut microbiota post DCH treatment were then investigated using 16S rRNA sequencing. Additionally, serum untargeted metabolomics were performed to examine the metabolic regulations of DCH on NAFLD. Our results showed that DCH treatment improved the dyslipidemia, insulin resistance (IR) and ameliorated pathological changes in NAFLD model rats. 16S rRNA sequencing and untargeted metabolomics showed significant dysfunction in gut microbiota community and serum metabolites in NAFLD model rats. DCH treatment restored the dysbiosis of gut microbiota and improved the dysfunction in serum metabolism. Correlation analysis indicated that the modulatory effects of DCH on the arachidonic acid (AA), glycine/serine/threonine, and glycerophospholipid metabolic pathways were related to alterations in the abundance of Romboutsia, Bacteroides, Lactobacillus, Akkermansia, Lachnoclostridium and Enterobacteriaceae in the gut microflora. In conclusion, our study revealed the ameliorative effects of DCH on NAFLD and indicated that DCH’s function on NAFLD may link to the improvement of the dysbiosis of gut microbiota and the modulation of the AA, glycerophospholipid, and glycine/serine/threonine metabolic pathways.

Highlights

  • Accumulating numbers of studies have shown that the dysbiosis in gut microbiota could contribute to the development of nonalcoholic fatty liver disease (NAFLD) (Stefano et al, 2018)

  • Our results showed that the level of PC was decreased and the level of PE was increased in NAFLD model rats, with the inverse effect following DCH treatment

  • Our study revealed the various ameliorative effects of DCH on NAFLD, including reducing the hepatic steaosis, improving dyslipidemia and insulin resistance (IR), and enhancing the liver’s anti-oxidative abilities

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Summary

Introduction

Accumulating numbers of studies have shown that the dysbiosis in gut microbiota could contribute to the development of nonalcoholic fatty liver disease (NAFLD) (Stefano et al, 2018). The composition of gut microbiota in NAFLD patients exhibited a distinct profile when compared to healthy controls (Li et al, 2018). Redundancy analysis (RDA) has revealed significant correlations between fecal microbiota and related clinical outcomes, such as insulin resistance (IR) and dyslipidemia (Li et al, 2018). Modulation of gut microbiota using probiotics has shown beneficial effects on NAFLD mice. The oral treatment of Lactobacillus rhamnosus GG was able to protect mice from NAFLD by inhibiting the inflammatory response and improving the gut barrier function (Ritze et al, 2014)

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