Pharmacomicrobiomics and the gut-brain axis: microbial modulation of drug response in brain disorders

Pharmacomicrobiomics is the study of how the gut microbiota affects the metabolism, efficacy, and safety of drugs. Gut microbes play a key role in neurochemical communication along the gut-brain axis and can alter responses to neuroactive medications. Dysbiosis alters pharmacodynamics by modulating the synthesis of neurotransmitters, immune function and neuroinflammation. Concurrently, it alters pharmacokinetics through microbial biotransformation, which directly changes drug bioavailability, activation, and clearance. Increasing evidence shown an association between variations in microbiome and differences in response to treatment in brain disorders. By integrating pharmacomicrobiomics into neuropharmacology, there are opportunities to achieve precision medicine by optimising therapy selection. This review emphasizes the importance of the gut microbiome in controlling drug response and highlights emerging microbiome-targeted approaches aiming to improve therapeutic efficacy and reduce adverse effects in neuropsychiatric and neurodegenerative disorders.