Doxycycline pre-exposure prophylaxis (doxyPrEP) has shown potential in preventing bacterial sexually transmitted infections, but the impact on the microbiome is unknown. This study assessed rectal microbiome changes over 48 weeks in 41 participants on HIV PrEP (tenofovir disoproxil fumarate/emtricitabine) enrolled in an open-label, randomized pilot trial comparing immediate (100 mg PO daily started immediately and continued to week 48) versus deferred doxyPrEP (100 mg PO daily starting at week 24, continued to week 48) in HIV-negative gay and bisexual men (Clinical Trial #: NCT02844634). Primary study outcomes included feasibility, adherence, and tolerability of the dual PrEP regimen, while exploratory outcomes included rectal microbiome changes. We performed 16S rRNA sequencing from participants that collected baseline, week 24, and week 48 samples. Microbial composition did not significantly change over time in either study arm as measured by individual taxa levels, or alpha and beta diversity at the genus level. A slight decrease ( < 10%) in alpha diversity was observed at the phylum level in the immediate arm, but not the deferred arm. This study shows doxyPrEP use results in minimal compositional changes in the microbiome over 12 months. Further research is needed to explore the impact of doxycycline for STI prevention on microbiome function and antimicrobial resistance.
© 2025. The Author(s).