Gut Microbiota and Metabolomic Changes In Type 2 Diabetes Mellitus: Insights From 16S rDNA Sequencing and...

The global rise in type 2 diabetes mellitus (T2DM) underscores the need to better understand its underlying biological mechanisms, particularly those involving host-microbiome interactions. This study aimed to characterize gut microbial diversity, taxonomic composition, and predicted metabolic pathways in newly diagnosed T2DM patients compared with the non-diabetic matched (NM) group. Fresh stool samples were analyzed using 16S rDNA sequencing. Alpha diversity (Chao, ACE, Shannon, and Simpson indices) and beta diversity were calculated to assess microbial community structure. Taxonomic differences were evaluated using Wilcoxon rank-sum tests and linear discriminant analysis effect size (LEfSe). Functional pathway prediction was performed using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) based on KEGG and MetaCyc annotations. Mendelian randomization (MR) analysis, including inverse-variance weighting, MR-Egger, and weighted median methods, was applied to assess genetically predicted associations between microbial taxa and T2DM. Results showed reduced microbial richness, as reflected by lower Chao and ACE indices, and altered diversity structure, as reflected by lower Shannon and higher Simpson indices, in T2DM patients, accompanied by significant compositional shifts. Increased relative abundance of Proteobacteria and decreased abundance of beneficial taxa such as Lachnospiraceae and Blautia were observed. Functional prediction indicated reduced abundance of pathways related to the non-oxidative pentose phosphate pathway, isobutanol biosynthesis, and L-isoleucine biosynthesis. MR analysis provided complementary evidence supporting associations between specific microbial taxa and T2DM susceptibility. In conclusion, T2DM is associated with reduced microbial richness, altered diversity structure, and distinct taxonomic and functional changes. These findings highlight the relevance of gut microbiota in T2DM and support the potential utility of microbiome-based biomarkers and therapeutic strategies. Further studies are required to validate these findings and clarify underlying mechanisms.