Over the past decades, medication use has steadily increased worldwide, with individuals frequently taking multiple medications (polypharmacy), often repeatedly over extended periods of time (1). Yet, our understanding of how these practices impact the gut microbiome, a key component to our health, remains in its infancy (2). A landmark in vitro study (3) profiling the effects of over 1,000 marketed drugs on representative human gut bacterial isolates found that 78% of antibiotics and 24% of human-targeted drugs affected commensal bacteria, including keystone species such as butyrate and propionate producers. More recently, another in vitro study (4) revealed that beta-blockers (used to treat hypertension), selective serotonin reuptake inhibitors (SSRIs, a class of antidepressants), and statins (used to reduce cholesterol levels) alter bacterial functions relevant to the host’s health, such as vitamin biosynthesis. Metagenomic in vivo studies (5–8) have further confirmed that commonly prescribed medications, such as metformin (antidiabetic), proton-pump inhibitors (used to decrease stomach acid production), and statins, can significantly alter the human gut microbiome composition and function, often in a dose-dependent manner. In addition, such medication-induced shifts have been shown to confound disease-associated microbial signatures (7), potentially hindering biomarker discovery. However, far less is known about the persistence of these alterations in the human gut over long periods of time (>1 year).

To explore the long-term impact of medication use on the gut microbiome, Aasmets et al. (9) integrated metagenomic profiling of stool samples from a previously published cohort of 2,509 individuals (10) with detailed past medication data extracted from electronic health records (EHR) (Fig. 1). EHR allowed the authors to characterize participants’ current and past medication use, up to 5 years prior to microbiome sampling.