Pi-Dan-Jian-Qing Decoction Ameliorates Type 2 Diabetes Mellitus Through Regulating the Gut Microbiota and Serum Metabolism.

Xuehua Xie,Zhaiyi Zhang,Weibo Wen,Hongwu Wang,Jie Zhao,Jinmei Gao,Huantian Cui,Jiabao Liao,Fei Qu,Yuanliang Ai,Chao Xu

doi:10.3389/fcimb.2021.748872

Abstract

Pi-Dan-Jian-Qing decoction (PDJQ) can been used in the treatment of type 2 diabetes mellitus (T2DM) in clinic. However, the protective mechanisms of PDJQ on T2DM remain unknown. Recent studies have shown that the changes in gut microbiota could affect the host metabolism and contribute to progression of T2DM. In this study, we first investigated the therapeutic effects of PDJQ on T2DM rats. 16S rRNA sequencing and untargeted metabolomics analyses were used to investigate the mechanisms of action of PDJQ in the treatment of T2DM. Our results showed that PDJQ treatment could improve the hyperglycemia, hyperlipidemia, insulin resistance (IR) and pathological changes of liver, pancreas, kidney, and colon in T2DM rats. PDJQ could also decrease the levels of pro-inflammatory cytokines and inhibit the oxidative stress. 16S rRNA sequencing showed that PDJQ could decrease the Firmicutes/Bacteroidetes (F to B) ratio at the phylum level. At the genus level, PDJQ could increase the relative abundances of Lactobacillus, Blautia, Bacteroides, Desulfovibrio and Akkermansia and decrease the relative abundance of Prevotella. Serum untargeted metabolomics analysis showed that PDJQ could regulate tryptophan metabolism, histidine metabolism, tricarboxylic acid (TCA) cycle, phenylalanine, tyrosine and tryptophan biosynthesis and tyrosine metabolism pathways. Correlation analysis indicated that the modulatory effects of PDJQ on the tryptophan metabolism, histidine metabolism and TCA cycle pathways were related to alterations in the abundance of Lactobacillus, Bacteroides and Akkermansia. In conclusion, our study revealed the various ameliorative effects of PDJQ on T2DM, including improving the liver and kidney functions and alleviating the hyperglycemia, hyperlipidemia, IR, pathological changes, oxidative stress and inflammatory response. The mechanisms of PDJQ on T2DM are likely linked to an improvement in the dysbiosis of gut microbiota and modulation of tryptophan metabolism, histamine metabolism, and the TCA cycle.

Highlights

Type 2 diabetes mellitus (T2DM) is a complex endocrine disease caused by a combination of environmental and genetic factors, leading to islet failure or insufficient insulin action
Our results showed that Pi-Dan-Jian-Qing decoction (PDJQ) treatment could improve the hyperglycemia, hyperlipidemia, insulin resistance (IR) and pathological changes of liver, pancreas, kidney, and colon in T2DM rats
Astragaloside in ragalus mongholicus Bunge, heterophyllin B in Pseudostellaria heterophylla (Miq.) Pax, atractylodin in Atractylodes lancea (Thunb.) DC., harpagide in Scrophularia ningpoensis Hemsl., berberine in Coptis chinensis Franch., baicalin in Scutellaria baicalensis Georgi, puerarin in Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, quercetin in Potentilla discolor Bunge, protocatechuic acid in Litchi chinensis Sonn. and tanshinone II A in Salvia miltiorrhiza Bunge were identified as the preeminent compounds in PDJQ

Summary

Introduction

Type 2 diabetes mellitus (T2DM) is a complex endocrine disease caused by a combination of environmental and genetic factors, leading to islet failure or insufficient insulin action. The intestinal microbiota can maintain the homeostasis of host glucose and lipid metabolism by digesting and absorbing food and producing metabolites (Ortega et al, 2020). Compared with the status in healthy people, the abundances of many probiotic bacteria including Lactobacillus and Akkermansia are decreased in the intestine of T2DM patients, while some harmful bacteria such as Enterobacteriaceae are increased (Tanase et al, 2020). The abnormal levels of metabolites caused by intestinal microbiota disorder are closely related to inflammatory reactions, insulin resistance (IR), as well as the disorders of glucose and lipid metabolism (Chávez-Carbajal et al, 2020). Study have demonstrated that metformin could regulate the abundances of Bacteroidetes, Escherichia, and other microbiota, maintaining the integrity of the intestinal barrier, promoting the production of short-chain fatty acids (SCFAs), and regulating bile acid metabolism, thereby showing hypoglycemic effects (Zhang and Hu, 2020)

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