Metagenome-assembled genomes from the gut microbiome of spontaneous diabetic macaques provide insights into microbes associated with type 2 diabetes mellitus

Gut microbiota plays a crucial role in type 2 diabetes mellitus (T2DM) pathogenesis. Spontaneous T2DM macaques offer a valuable model for investigating contributions of gut microbiota to T2DM pathogenesis due to physiological similarities to humans and the absence of glucose-lowering drug interference. We performed de novo assembly of metagenome-assembled genomes (MAGs) to explore the diversity and function of the gut microbiome at the genome level. We obtained 317 non-redundant MAGs from fecal metagenomes of macaques and 325 MAGs from humans, 168 of which were potential novel species. Most members of Lachnospiraceae, the main carriers of carbohydrate-active enzymes (CAZymes) and virulence genes, significantly increased in the guts of T2DM macaques and unmedicated T2DM patients. Further analysis on the MAGs of Lachnospiraceae identified concordant enrichment of potential microbial signatures of T2DM, including the macaque-derived Eubacterium_Q sp900314445 (Mm_bin23) and human-derived Eubacterium_F sp003491505 (Hs_bin20) and Eubacterium ramulus (Hs_bin147). They all carried intestinal barrier-associated virulence genes and diabetes-associated hypervirulence genes, which might be associated with barrier dysfunction, inflammation, and disrupt glucose homeostasis, thereby potentially contributing to the pathogenesis of T2DM. This study assembled extensive MAGs from the gut microbiome of spontaneous T2DM macaques and asymptomatic controls. Furthermore, we identified three Eubacterium genomes harboring virulence genes and diabetes-associated genes, which were significantly enriched in both T2DM macaques and T2DM humans, highlighting the potential roles of these microbes in T2DM pathogenesis. Overall, this study provides a critical foundation for elucidating gut microbiome-mediated mechanisms and developing targeted therapeutic strategies for T2DM.