a Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
b Faculty of Biological Science and Technology, Baotou Teacher's College, Baotou, Inner Mongolia 014030, China
c CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
d Infinitus (China) Company Ltd, Guangzhou, Guangdong 510405, China
e The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, China
f Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
g Xinjiekou Community Health Service Center in Xicheng District, Beijing 100035, China
h Department of Spleen and Stomach, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518033, China
i University of Chinese Academy of Sciences, Beijing 100049, China
j Beijing University of Chinese Medicine, Beijing 100105, China
k Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
Funds:
This study was supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine. (ZYYCXTD-D-202001) and the National Natural Science Foundation of China (82104835).
Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders; however, comprehensive studies on impaired glucose tolerance (IGT), a diabetes mellitus (DM) precursor, are lacking. Here, we perform metagenomic sequencing and metabolomics of 47 pairs of individuals with IGT and newly diagnosed DM, and 46 controls with normal glucose tolerance (NGT); patients with IGT are followed-up after 4 years for progression to DM. Analysis of baseline data reveal significant differences in gut microbiota and serum metabolites among the IGT, DM, and NGT groups. In addition, 13 types of gut microbiota and 17 types of circulating metabolites show significant differences at baseline before IGT progressed to DM, including higher levels of Eggerthella unclassified, Coprobacillus unclassified, Clostridium ramosum, L-valine, L-norleucine, and L-isoleucine, and lower levels of Eubacterium eligens, Bacteroides faecis, Lachnospiraceae bacterium 3_1_46FAA, Alistipes senegalensis, Megaspaera elsdenii, Clostridium perfringens, α-linolenic acid, 10E,12Z octadecadienoic acid, and dodecanoic acid. A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM (AUC = 0.87). These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.
DownLoad: