Tian Chaoyang, Yang Qunhui, Lv Haizhou, Yue Feng
Sanya Research Institute of Hainan University, School of Biomedical Engineering, Hainan University, Sanya, 572025, China; Key Laboratory of Biomedical Engineering of Hainan Province, One Health Institute, Hainan University, Haikou, 570228, China.
Hainan Jingang Biotech Co., Ltd, Haikou, 570100, China.
Microb Pathog. 2025 Feb;199:107228. doi: 10.1016/j.micpath.2024.107228. Epub 2024 Dec 13.
Accumulating evidence suggests that gut microbiota (GM) is clearly associated with the pathogenesis of type 2 diabetes mellitus (T2DM). However, the underlying mechanism of GM dysbiosis participates the onset of T2DM is not fully understood. The spontaneous T2DM cynomolgus monkeys are a powerful model for understanding the pathological mechanism of T2DM.
Fecal samples were collected from 7 spontaneous T2DM cynomolgus monkeys and 7 healthy controls matched with similar age for multi-omics analysis, including shotgun metagenomic sequencing, untargeted metabolomics profiling, and targeted metabolomics focusing on short chain fatty acids (SCFAs). Lastly, the correlation network between differential gut microbial species and fecal metabolites was performed to explore the potential biomarkers of T2DM.
We found that 17 low-abundance species showed significant differences between the two groups. Analysis of gut microbial functions revealed that 16 KEGG pathways and 51 KEGG modules were significantly different in the two groups. Meanwhile, 276 fecal DEMs were identified, and these DEMs were enriched in the KEGG pathways, including Nucleotide metabolism, ABC transporters, Purine metabolism and so on. Lastly, Spearman correlation network analysis showed that the species of Anaerostipes_hadrus and Lachnoanaerobaculum_umeaense, and the metabolites including Glycerophospho-N-palmitoyl ethanolamine and 2-Hydroxycinnamic acid might serve as potential biomarkers of T2DM.
Our study provides novel insights into specific alterations in the GM composition, gene functions, and fecal metabolic profiles in spontaneous T2DM cynomolgus monkeys.
越来越多的证据表明，肠道微生物群（GM）与2型糖尿病（T2DM）的发病机制密切相关。然而，GM失调参与T2DM发病的潜在机制尚未完全明确。自发性T2DM食蟹猴是理解T2DM病理机制的有力模型。
收集7只自发性T2DM食蟹猴和7只年龄匹配的健康对照的粪便样本进行多组学分析，包括鸟枪法宏基因组测序、非靶向代谢组学分析以及针对短链脂肪酸（SCFAs）的靶向代谢组学分析。最后，构建差异肠道微生物物种与粪便代谢物之间的相关网络，以探索T2DM的潜在生物标志物。
我们发现两组之间有17种低丰度物种存在显著差异。肠道微生物功能分析显示，两组之间有16条KEGG通路和51个KEGG模块存在显著差异。同时，鉴定出276种粪便差异表达代谢物（DEMs），这些DEMs在KEGG通路中富集，包括核苷酸代谢、ABC转运蛋白、嘌呤代谢等。最后，Spearman相关网络分析表明，哈氏厌氧棒状菌和乌梅拉氏厌氧芽孢杆菌物种以及包括甘油磷酸-N-棕榈酰乙醇胺和2-羟基肉桂酸在内的代谢物可能是T2DM的潜在生物标志物。
我们的研究为自发性T2DM食蟹猴的GM组成、基因功能和粪便代谢谱的特定改变提供了新的见解。
