Integrative analysis of gut microbiota and metabolic pathways reveals key microbial and metabolomic alterations in diabetes

Abstract

Abstract Type 2 diabetes mellitus (T2DM) is increasingly recognized as a condition influenced by gut microbiota composition and associated metabolic pathways. This study investigated the differences in gut microbial diversity, composition, and metabolomic profiles between diabetic and control individuals. Using 16 S rRNA gene sequencing and metabolomic analyses, we observed significantly higher microbial diversity and evenness in the diabetic group, with distinct clustering patterns as revealed by Principal Coordinate Analysis (PCoA). Taxonomic profiling demonstrated an increased relative abundance of Bacteroidaceae and Lachnospiraceae in the diabetic group, while Streptococcaceae was more prevalent in the control group. LEfSe analysis identified key microbial taxa such as Bacteroides, Blautia, and Lachnospiraceae_FCS020_group enriched in diabetic individuals, suggesting a role in metabolic dysregulation. Metabolomic pathway enrichment analysis revealed significant differences in pathways related to fatty acid metabolism, glucose homeostasis, bile acid metabolism, and amino acid biosynthesis in diabetic individuals. Enriching fatty acid elongation and β-oxidation pathways, alongside disrupted glucose metabolism, indicate profound metabolic changes associated with diabetes. Bile acid metabolism and branched-chain amino acid (BCAA) pathways were also elevated, linking these metabolites to the observed gut microbiota shifts. These findings suggest that diabetes is associated with significant alterations in the gut microbiome’s composition and function, leading to disruptions in critical metabolic pathways. This study provides insights into potential microbial biomarkers and therapeutic targets for improving metabolic health in diabetic patients.