Abstract

BackgroundThe current work aimed to assess whether Gynostemma pentaphyllum (GP), a Chinese herbal medicine, structurally modifies the gut microbiota in rats during non-alcoholic fatty liver disease (NAFLD) treatment.MethodsHigh-fat diet (HFD)-induced NAFLD rats were orally administered water decoction of GP or equal amounts of distilled water per day for 4 weeks. Liver tissues were examined by histopathological observation, while intestinal tissues were examined by both histopathological and ultrastructural observations. The levels of fasting blood glucose (FBG), fasting serum insulin (FINS), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) were measured by enzymatic method. The levels of toll-like receptor 4 (TLR-4), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and interleukin-6 (IL-6) in both serum and hepatic tissues were measured by RT-qPCR. The protein expression level of TLR-4 in hepatic tissues was detected by western blot. The gut microbiota was assessed by 16S rRNA-based microbiota analysis.ResultsGP maintained intestinal integrity and reversed gut dysbiosis in high-fat diet (HFD)-induced NAFLD rats. This also reduced the ratio of Firmicutes to Bacteroidetes, enriching the abundance of beneficial bacteria (Lactococcus spp.) and inhibiting the abundance of pathogenic bacteria (Ruminococcus spp.) in the gut. The levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and the expression of TLR4 were downregulated (P < 0.05), while the insulin resistance index, HOMA-IR showed improvement by GP treatment (P < 0.05). Liver function indicators (ALT and AST) were remarkably decreased (P < 0.01). Besides, GP treatment reduced TG and LDL-C levels (P < 0.05), and increased HDL-C level (P < 0.05) compared with NAFLD group.ConclusionThe structural alterations of gut microbiota induced by GP are associated with NAFLD alleviation.

Highlights

  • The current work aimed to assess whether Gynostemma pentaphyllum (GP), a Chinese herbal medicine, structurally modifies the gut microbiota in rats during non-alcoholic fatty liver disease (NAFLD) treatment

  • GP prevents high-fat diet (HFD)-induced hyperlipidemia of NAFLD Previous studies showed that the rats fed a HFD produced high levels of total cholesterol (TC), TG and low-density lipoprotein cholesterol (LDL-C), while the production of high-density lipoprotein cholesterol (HDL-C) was reduced [31, 32]

  • dilinoleoyl phosphatidylcholine (DLPC) treatment reduced the serum TG and LDL-C levels, and increased HDL-C level as expected. These findings suggested that GP prevents HFD-induced hyperlipidemia in rats (Table 1)

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Summary

Introduction

The current work aimed to assess whether Gynostemma pentaphyllum (GP), a Chinese herbal medicine, structurally modifies the gut microbiota in rats during non-alcoholic fatty liver disease (NAFLD) treatment. NAFLD represents a group of ailments, ranging between simple steatosis and non-alcoholic steatohepatitis (NASH), which at times lead to cirrhosis [3] It is considered one of the main factors causing liver disease worldwide, with a prevalence of around 25–45% [4]. The “multiple hit” hypothesis provides a relatively accurate explanation, wherein multiple insults act jointly in individuals with genetic predisposition to trigger NAFLD as well as associated complications. Such hits include insulin resistance, nutrition, gut microbiome, hormones secreted by the fat tissues, and genetic and epigenetic factors [10]. Dysbiosis increases gut permeability to bacterial products, promotes energy absorption, aggravates insulin resistance (IR), facilitating systemic bacterial translocation and hepatic inflammation [12]

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