Identification of Bacterial Key Genes and Therapeutic Targets in Hypertensive Patients with Type 2 Diabetes using Bioinformatics Analysis

Hypertension (HTN) coexisting with type 2 diabetes (T2D) significantly elevate the risk of cardiovascular complications and growing evidence suggests that gut microbiota may contribute to the development of these conditions. Yet, microbial gene-level insights in hypertensive patients with T2D (HTNT2D) are still limited. To address this gap, this study aimed to identify bacterial key genes (bKGs) associated with HTNT2D and to explore therapeutic agents targeting these bKGs through integrated bioinformatics approaches. This study analyzed 124 gut microbiome samples downloaded from NCBI which includes 95 healthy controls and 29 HTNT2D cases. After quality control, 92% of raw 16S rRNA reads were retained which yielded 53,311 representative OTUs. Building on this dataset, diversity analysis showed significantly higher microbial richness in HTNT2D and revealed distinct clustering between groups which indicates an altered microbial structure. Differential abundance analysis further identified 19 bacterial genera across four dominant phyla. Functional prediction then explored 195 enriched metabolic pathways and 139 associated genes. To refine these finding, protein–protein interaction analysis highlighted 10 hub genes (acpP, dnaG, fusA, gltB, guaA, gyrB, lacZ, mdh, purF and tktA) as potential drivers of HTNT2D pathogenesis. Molecular docking of these targets revealed three top-ranked drug candidates named Naringin-fusA, Neohesperidin-mdh, and Bromocriptine-gyrB and subsequent molecular dynamics simulations confirmed the stability of their complexes. Drug-likeness and ADMET evaluations pointed to Bromocriptine as the most suitable compound though further safety validation will be necessary. Overall, this study provides novel insights into the gut microbiome signatures of HTNT2D and identifies bKGs with therapeutic relevance. The findings highlight the promise of microbiome-based diagnostics and targeted drug strategies for managing patients with HTNT2D.