Microbiome-Drug Interaction Pharmacology: Influence of Gut Microbial Community Composition on Antibiotic Bioavailability and Efficacy in Nigerian Patient Populations

Emerging evidence demonstrates that gut microbial communities can profoundly alter the pharmacokinetics and pharmacodynamics of orally administered antibiotics through biotransformation, drug binding, efflux pumping, and alteration of intestinal transport. These microbiome-drug interactions have not been characterized in Nigerian populations despite their potential to explain inter-individual variability in antibiotic treatment outcomes. This study investigated the influence of gut microbial community composition on the bioavailability and in vivo pharmacodynamics of oral amoxicillin-clavulanate and ciprofloxacin in 80 adult patients at Obafemi Awolowo University Teaching Hospital (OAUTHC), Ile-Ife, Osun State, South West Nigeria. Gut microbiome profiling by 16S rRNA sequencing was performed from baseline stool samples. Serial plasma antibiotic concentrations were measured by HPLC at defined intervals following oral dosing to construct individual pharmacokinetic profiles. In vitro drug-microbiome interaction studies using ex vivo fecal incubation with antibiotic solutions quantified drug degradation capacity of individual patient microbiomes. Results showed significant inter-individual variability in ciprofloxacin bioavailability (Cmax range: 0.8 to 2.9 mg/L) and amoxicillin AUC (range: 8.4 to 31.2 mg*h/L). High relative abundance of Clostridiales order members significantly correlated with reduced ciprofloxacin Cmax (r: -0.52). Ex vivo incubation confirmed dose-dependent ciprofloxacin inactivation by diverse patient microbiomes. These findings generate an original pharmacomicrobiomic framework for antibiotic efficacy optimization and motivate further pharmacokinetic-pharmacodynamic modelling studies incorporating gut microbiome data. Keywords: pharmacomicrobiomics, gut microbiome, antibiotic bioavailability, pharmacokinetics, Nigeria.