Integrated 16S rRNA sequencing and metabolomic analysis reveals the potential protective mechanism of Germacrone on diabetic nephropathy in mice  

作　　者：Yunguang Wang Xinxin He Mengjiao Xue Huan Yu Qiang He Juan Jin 

机构地区：[1]Department of Nephrology,the First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Traditional Chinese Medicine),Hangzhou 310006,China [2]School of Clinical Medicine,Hangzhou Medical College,Hangzhou 311399,China [3]The Fourth Clinical Medical College,Zhejiang Chinese Medical University,Hangzhou 310053,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第3期414-426,共13页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project(No.2022ZB273);the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LHDMY24H270002);the Zhejiang Provincial Medical and Health Technology Project(No.2023KY158);the Cultivation Program for Excellent Young Talents of Hangzhou First People’s Hospital(No.YQNYC202131);the Science and Technology Special Project of Hangzhou Biomedicine and Health Industry Development Support(No.2021WJCY253).

摘　　要：Diabetic nephropathy(DN)is a severe complication of diabetes and the leading cause of end-stage renal disease and death.Germacrone(Ger)possesses anti-inflammatory,antioxidant and anti-DN properties.However,it is unclear whether the improvement in kidney damage caused by Ger in DN mice is related to abnormal compositions and metabolites of the gut microbiota.This study generates a mouse model of DN to explore the potent therapeutic ability and mechanism of Ger in renal function by 16S rRNA sequencing and untargeted fecal metabolomics.Although there is no significant change in microbiota diversity,the structure of the gut microbiota in the DN group is quite different.Serratia_marcescens and Lactobacillus_iners are elevated in the model group but significantly decreased after Ger intervention(P<0.05).Under the treatment of Ger,no significant differences in the diversity and richness of the gut microbiota are observed.An imbalance in the intestinal flora leads to the dysregulation of metabolites,and non-targeted metabolomics data indicate high expression of stearic acid in the DN group,and oleic acid could serve as a potential marker of the therapeutic role of Ger in the DN model.Overall,Ger improves kidney injury in diabetic mice,in part potentially by reducing the abundance of Serratia_marcescens and Lactobacillus_iners,as well as regulating the associated increase in metabolites such as oleic acid,lithocholic acid and the decrease in stearic acid.Our research expands the understanding of the relationship between the gut microbiota and metabolites in Ger-treated DN.This contributes to the usage of natural products as a therapeutic approach for the treatment of DN via microbiota regulation.

关 键 词：diabetic nephropathy GERMACRONE gut microbiota untargeted fecal metabolomics 16S rRNA sequencing 

分 类 号：R587.2[医药卫生—内分泌] R692[医药卫生—内科学]