Investigating the Role of the Gut Microbiome in Modulating Antidiabetic Drug Efficacy in Nigerian Type 2 Diabetic Patients: A Metagenomics and Metabolomics Investigation

Background: Emerging evidence indicates that the gut microbiome plays a significant role in modulating the pharmacological efficacy of antidiabetic drugs, particularly metformin, through effects on drug metabolism, glucose homeostasis, and short-chain fatty acid production. However, microbiome composition is highly population-specific, and no study has investigated the gut microbiome-antidiabetic drug efficacy relationship in Nigerian patients. This study characterises gut microbiome profiles and their relationship with antidiabetic drug response in Nigerian type 2 diabetic patients. Methods: Stool samples were collected from 150 type 2 diabetic patients stratified by glycaemic response to metformin (responders vs non-responders) at clinics in Ibadan and Abuja. Gut microbiome profiling was performed by 16S rRNA amplicon sequencing. Plasma metabolomics was conducted by LC-MS to identify microbiome-derived metabolites. Metagenome-assembled genomes were analysed for drug-metabolising microbial genes. Spearman correlation and random forest modelling linked microbiome features to HbA1c outcomes. Results: Metformin responders showed significantly higher relative abundance of Lactobacillus, Bifidobacterium, and Akkermansia muciniphila. Non-responders were enriched in Ruminococcus gnavus. Short-chain fatty acid-producing capacity correlated positively with HbA1c reduction (rho = -0.52). Three microbial gene clusters involved in metformin biotransformation were identified as significant predictors of response. Conclusion: Gut microbiome composition is a significant determinant of metformin efficacy in Nigerian diabetic patients. Microbiome-guided personalised antidiabetic prescribing represents a promising precision medicine frontier. Keywords: gut microbiome, metformin, type 2 diabetes, metagenomics, precision pharmacology