Long-term consequences of drug usage on the gut microbiome

Medication usage is a significant contributor to the inter-individual variability in the gut microbiome. However, drugs are often used long-term and repeatedly, a notion yet unaccounted for in microbiome studies, which might lead to underestimating the extent of drug effects. Recently, we and others showed that not only the usage of antibiotics and antidepressants at the time of sampling but also past consumption is associated with the gut microbiome. This effect can be "additive" - the more a drug is used, the stronger the effect on the microbiome. Here, by utilizing electronic health records and the Estonian Microbiome cohort metagenomics dataset (n=2,509), we systematically evaluate the long-term effects of antibiotics and human-targeted medications on the gut microbiome. We show that the past usage of medications is associated with the gut microbiome, and for example, the effects of antibiotics, psycholeptics, antidepressants, proton pump inhibitors, and beta-blockers are detectable several years after usage. Furthermore, by analyzing a subcohort (n=328) with microbiome measured repeatedly, we show that similar changes in the gut microbiome occur after treatment initiation, possibly indicating causal effects.