Integrative analysis of gut microbiota and fecal metabolites in cynomolgus monkeys with spontaneous type 2 diabetes mellitus

Background: 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. Methods: 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. Results: 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. Conclusions: Our study provides novel insights into specific alterations in the GM composition, gene functions, and fecal metabolic profiles in spontaneous T2DM cynomolgus monkeys.