Abstract:
Pharmacomicrobiomics, an emerging field at the intersection of microbiology and pharmacology, explores the intricate relationship between drug response and the gut microbiome, offering new avenues for precision medicine. Lifestyle factors, including diet, exercise, smoking, and alcohol consumption, significantly influence drug metabolism and clearance, adding to the complexity of individual variability in drug response. Recent studies have investigated the impact of medications used for various diseases on the gut microbiome; however, categorized medications by class, a comprehensive understanding of microbiome-drug interactions with drug-specific structural characteristics is still unclear. Moreover, existing literature often focuses on specific therapeutic areas such as non-steroidal anti-inflammatory drugs (NSAIDs), anti-diabetic agents, and cancer therapeutics, overlooking the diverse chemical structures of drugs within each category. This study aims to identify the complex relationships between medication structure, gut microbiota composition, and host factors. We performed meta-analysis across more than 10 global cohorts encompassing > 6000 subjects. Additionally, we identify non-antibiotic medication associated modules of gut microbial taxa that show distinct associations with different drug classes. These drug-responsive modules also show differential enrichment of markers of health and disease, indicating that while certain drugs have a minimal or beneficial impact on the gut microbiomes, others can potentially drive the gut microbiome to a detrimental state. Furthermore, our findings highlight the pivotal role of cohort lifestyle, particularly industrialized living, in shaping bacterial species’ response to drugs, underscoring the need for holistic approaches in understanding drug-microbiome interactions. Findings from this study can inform public health guidelines regarding the prescription and usage of different non-antibiotic drugs across global populations.
