Nature Medicine Study Highlights Impact of Doxycycline-Post Exposure Prophylaxis for STI on Gut Microbiome - Video

Taking a dose of the oral antibiotic doxycycline after a high-risk sexual encounter has dramatically reduced the incidence of sexually transmitted infections (STIs) in places where the strategy is being tried.

Despite its effectiveness, the new strategy, known as Doxycycline post-exposure prophylaxis, may come with risks, especially with chronic use. Experts worry about the impact on the community of gut bacteria, also known as the microbiome, and the potential that the antibiotic will give rise to resistant strains of bacteria. 

Doxycycline post-exposure prophylaxis did not have much impact on the overall composition of bacterial communities in gastrointestinal tracts. But scientists noted signs of resistance building against tetracycline, the class of antibiotic that doxycycline belongs to, which could make it less effective. 

The study was published in Nature Medicine.

“While doxycycline post-exposure prophylaxis did not appear to have global impacts on the gut microbiome, it did have impacts on the antimicrobial resistance of gut bacteria, both in terms of the proportion of tetracycline class resistance genes and the amount that were turned on, or expressed,” said Chaz Langelier, MD, PhD, an associate professor of medicine in UCSF’s Division of Infectious Diseases and senior author of the paper. “So, it's not totally innocuous.”    

Doxycycline post-exposure prophylaxis involves taking two 100-milligram pills within 72 hours of condomless sex.

But the widespread use of antibiotics raises concerns about resistance and the potential harmful impact on gut health, specifically the balance of bacteria and other microbes. Disruption can lead to diarrhea, nausea, fever and abdominal pain; and until now, there had been very limited research into these side effects. 

The study included 100 individuals who used doxycycline post-exposure prophylaxis and 50 individuals who received standard-of-care and did not use doxycycline post-exposure prophylaxis. Researchers analyzed rectal swabs collected at enrollment and after six months to study the presence of DNA and RNA from gut bacteria and their antibiotic resistance genes.

“While we found no major changes to the community of gut bacteria in doxycycline post-exposure prophylaxis users, we saw that doxycycline post-exposure prophylaxis users over time had increasing amounts of tetracycline resistance genes present in their gut,” said Victoria T. Chu, MD, MPH, an assistant professor of pediatrics in the Division of Global Health and Infectious Diseases at UCSF and a first author of the study. “It also appeared to be dose dependent, meaning the more doxycycline post-exposure prophylaxis they used, the larger the increase was.” 

Reference: Chu, V.T., Glascock, A., Donnell, D. et al. Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome. Nat Med (2024). https://doi.org/10.1038/s41591-024-03274-2