Gut Microbiome Dysbiosis in Type 2 Diabetes Shows Sex-Associated Shifts in Microbial Composition and Metabolic Pathways

Abstract

Type II diabetes mellitus (T2DM) is a chronic disease characterized by the body's inability to respond to insulin and regulate blood glucose levels. Previous research has shown a link between gut microbiome dysbiosis and T2DM. Certain microbial species have been shown to be enriched in T2DM, along with a reduction of short-chain fatty acid (SCFA)-producing and butyrate-producing species. Biological sex is well known to play a role in T2DM development and progression and should be taken into consideration when studying this disease. However, the sex-specific taxonomic and functional differences of the gut microbiome in diabetic and pre-diabetic individuals are less understood. In this study, a dataset consisting of Colombian stool samples was filtered to classify individuals as non-diabetic, pre-diabetic, or diabetic, and investigate microbiome differences. Both diabetic and non-diabetic females displayed increased alpha and beta diversity compared to diabetic and non-diabetic males respectively, while non-significant differences were observed in alpha and beta diversity in pre-diabetic individuals. Core microbiome and indicator species analyses revealed diabetic males had decreased relative abundance of beneficial bacteria. Furthermore, diabetic males showed an increased representation of various degradation pathways of anti-hyperglycemic metabolites compared to diabetic females. Altogether, this study suggests diabetic males display greater gut dysbiosis than diabetic females, which potentially contributes to T2DM disease development and progression.