A hidden confounder for microbiome studies: medications used years before sample collection

Area of Science:

• Microbiome Research
• Pharmacology
• Human Health

Background:

• Medication use is a key factor in gut microbiome variability.
• Previous studies often overlook the long-term and cumulative effects of medication on the microbiome.
• The impact of past medication consumption on the gut microbiome is increasingly recognized.

Purpose of the Study:

• To systematically evaluate the long-term effects of antibiotic and human-targeted medication use on the gut microbiome.
• To investigate the additive and carryover effects of medications on gut microbial composition.
• To explore potential causal links between medication use and microbiome changes.

Main Methods:

• Utilized retrospective medication usage data from electronic health records.
• Analyzed shotgun metagenomics data from the Estonian microbiome cohort (n = 2,509).
• Examined a subcohort (n = 328) with longitudinal microbiome data to assess changes post-treatment initiation/discontinuation.

Main Results:

• Past medication usage, including antibiotics, psycholeptics, antidepressants, proton pump inhibitors, and beta-blockers, is significantly associated with the gut microbiome.
• These medication-induced microbiome alterations are detectable for several years after cessation of use.
• Similar microbiome changes were observed upon both treatment initiation and discontinuation, suggesting potential causal relationships.

Conclusions:

• This study provides the first systematic assessment of long-term medication effects on the gut microbiome using detailed electronic health record data.
• Carryover and additive effects were identified for various drug classes, including antibiotics, benzodiazepine derivatives, antidepressants, and glucocorticoids.
• The findings underscore the collateral impact of diverse medications on the gut microbiome and emphasize the need to incorporate medication history into disease-microbiome association studies.