Alleviation Effects of GQD, a Traditional Chinese Medicine Formula, on Diabetes Rats Linked to Modulation of the Gut Microbiome.

Jiaxing Tian,Xinmiao Wang,Bingbing Bai,Haoran Wu,Min Li,Zezheng Gao,Xiaolin Tong,Yingying Yang,Jun Wang

doi:10.3389/fcimb.2021.740236

Abstract

Gegen Qinlian Decoction (GQD) is a Chinese herbal medicine that has been reported to significantly decrease blood glucose levels, which is suggested to be related to interactions with the gut microbiota. However, the protective effect of GQD on intestinal barrier function with regard to its influence on the gut microbiota has not been explored to date. In this study, we investigated the role of the gut microbiota in mediating the hypoglycemic mechanism of GQD in type 2 diabetes mellitus (T2DM) rats induced by a single intraperitoneal injection of streptozotocin after 4 weeks of high-fat diet feeding. The T2DM rats were randomly allocated to receive GQD, metformin (Met), or saline for 12 consecutive weeks, and changes in metabolic parameters, intestinal barrier function, and inflammation were investigated. Gut microbiota was analyzed using 16S rRNA gene sequencing from fecal samples, and statistical analyses were performed to correlate microbiota composition with phenotypes of the T2DM rats. GQD administration decreased the levels of blood glucose and inflammatory cytokines, and increased the levels of tight junction proteins. Besides, GQD had a protective effect on islet function, restoring intestinal permeability, and inhibiting inflammation, as evidenced by increases in the levels of serum C-peptide, occludin, and claudin-1 in the colon, and also improved the expression of serum inflammatory factors. In addition, GQD regulated the structure of the gut microbiota by increasing the proportions of short-chain fatty acids-producing and anti-inflammatory bacteria, and decreasing the proportions of conditioned pathogenic bacteria associated with the diabetic phenotype. Overall, these findings suggest that GQD could ameliorate hyperglycemia and protect islet function by regulating the structure of the gut microbiota, thereby restoring intestinal permeability and inhibiting inflammation in T2DM rats. Our study thus suggests that the hypoglycemic mechanism of GQD is mediated by its modulation of the gut microbiota.

Highlights

Gegen Qinlian Decoction (GQD), a classical prescription of traditional Chinese medicine, was first recorded in the book “Treatise on Febrile Diseases” in the Eastern Han Dynasty
Only GQD significantly decreased fasting plasma glucose at 8 and 10 weeks, and HbA1c at 12 weeks (Figures 1B, C, P < 0.01, P < 0.05), no significant difference was observed between the GQD and Met groups based on the analysis of variance (ANOVA) results
Our previous study demonstrated that GQD could decrease the blood glucose level and enrich the amounts of beneficial bacteria, and these structural changes of gut microbiota were associated with the anti-diabetes effects of GQD (Xu et al, 2015)

Summary

Introduction

Gegen Qinlian Decoction (GQD), a classical prescription of traditional Chinese medicine, was first recorded in the book “Treatise on Febrile Diseases” in the Eastern Han Dynasty. Risk factors for metabolic disorders such as lack of exercise and irregular eating habits result in dysfunction of the gut microbiota and turbulence of the internal environment with consequent destruction of the integrity of the intestinal barrier, allowing for the proliferation of opportunistic pathogens and pathogenic bacteria (Forslund et al, 2015). These effects induce chronic inflammatory reactions that disrupt metabolic balance (Cani et al, 2008; Cani and Delzenne, 2009). Some hypoglycemic drugs have been shown to function by interfering with the structure of the gut microbiota, such as metformin (Met) and acarbose (Gu et al, 2017; Wu et al, 2017)

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