Integrated gut microbiome and UHPLC-MS metabolomics to reveal the prevention mechanism of pidanjiangtang granules on IGT Rats

Yu Xie; Zirong Li; Yue Fan; Xinyi Liu; Ran Yi; Yaoyao Gan; Zixuan Yang; Shangjian Liu

doi:10.1016/j.phymed.2024.156201

Integrated gut microbiome and UHPLC-MS metabolomics to reveal the prevention mechanism of pidanjiangtang granules on IGT Rats

Phytomedicine. 2024 Nov 3:135:156201. doi: 10.1016/j.phymed.2024.156201. Online ahead of print.

Authors

Yu Xie¹, Zirong Li², Yue Fan¹, Xinyi Liu¹, Ran Yi¹, Yaoyao Gan¹, Zixuan Yang¹, Shangjian Liu³

Affiliations

¹ Beijing University of Chinese Medicine, Beijing, China; Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
² Beijing University of Chinese Medicine, Beijing, China.
³ Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China. Electronic address: dzmyylsj@163.com.

PMID: 39531936
DOI: 10.1016/j.phymed.2024.156201

Abstract

Introduction: Pidanjiangtang (PDJT) is a traditional Chinese medicine formula empirically used to treat impaired glucose tolerance (IGT) based on the "Pidan" theory from the classic ancient book Nei Jing. However, the mechanism of PDJT intervention for IGT remains to be studied.

Objective: This study aims to explore the mechanism of PDJT granules intervention in IGT by integrating gut microbiome and UHPLC-MS untargeted metabolomics.

Materials and methods: The IGT model was established in 6-week-old male Sprague-Dawley (SD) rats by feeding them a high-fat diet and using an STZ injection. The low, medium, and high doses of PDJT were used for six weeks. metformin (Glucophage) was used as the positive control drug. The efficacy of PDJT was evaluated using fasting blood glucose (FBG), blood glucose maximum (BGmax), blood lipid, and inflammatory factor levels. Finally, 16S rDNA gut microbiome sequencing with metabolomics analysis was used to explore the pharmacological mechanism of PDJT intervention in IGT.

Results: PDJT could reverse the phenotype of IGT rats, reduce blood glucose levels, improve lipid metabolism disorder, and reduce inflammatory response. Gut microbiome analysis found that PDJT can improve gut microbiota composition and abundance of three phyla (Firmicutes, Bacteroidota, Desulfobacterota) and four genera (unclassified_f__Lachnospiraceae, Ruminococcus, Allobaculum, Desulfovibrio), which play an important role in the process of PDJT intervention on glucose metabolism and lipid metabolism in IGT rats. UHPLC-MS untargeted metabolomics showed that PDJT could regulate the levels of 258 metabolites in lipid metabolism pathways, inflammatory response pathways, fat and protein digestion, and absorption. The combined analysis of the two omics showed that improving the body's metabolism by gut microbes may be the possible mechanism of PDJT in treating IGT. Thus, this study provides a new method to integrate gut microbiome and UHPLC-MS untargeted metabolomics to evaluate the pharmacodynamics and mechanism of PDJT intervention in IGT, providing valuable ideas and insights for future research on the treatment of IGT with traditional Chinese medicine.

Keywords: Gut microbiome(2); Impaired glucose tolerance(1); Medicine food homology(4); Pidanjiangtang granules(6); Traditional Chinese medicine(5); UHPLC-MS untargeted metabolomics(3).