A new strategy known as doxy-PEP, involving taking a dose of the oral antibiotic doxycycline after a high-risk sexual encounter, has been found to significantly reduce the incidence of sexually transmitted infections (STIs) in areas where it is being implemented. While this approach has proven effective, concerns have been raised regarding potential risks associated with chronic use, particularly in terms of its impact on the gut microbiome and the development of antibiotic-resistant bacteria. To address these concerns, researchers at UC San Francisco used metagenomic sequencing to examine the effects of doxycycline on the gut microbiome of individuals who took the antibiotic frequently for six months.
The study found that while doxy-PEP did not result in significant changes to the overall composition of bacterial communities in the gastrointestinal tracts of participants, there were indications of resistance building against tetracycline, the class of antibiotics to which doxycycline belongs. This resistance could potentially reduce the effectiveness of the antibiotic over time. The findings, published in the journal Nature Medicine, suggest that while doxy-PEP may not have global impacts on the gut microbiome, it can impact the antimicrobial resistance of gut bacteria, both in terms of the proportion of tetracycline class resistance genes and their expression.
San Francisco has taken a high-profile role in STI prevention by being the first city in the U.S. to recommend doxy-PEP for individuals at high risk of STIs, such as gay and bisexual men and transgender women with a history of unprotected encounters. Early results from clinical trials in the city showed promising outcomes, with a significant reduction in the incidence of chlamydia and early syphilis after about a year of implementing the strategy. Following these results, the U.S. Centers for Disease Control and Prevention (CDC) issued guidelines recommending the use of doxy-PEP for these groups, marking the adoption of the first new STI prevention tool in decades.
Researchers at UC San Francisco, in collaboration with the Chan Zuckerberg Biohub and scientists from other institutions, studied participants from recent doxy-PEP clinical trials in San Francisco and Seattle to assess the impact of the antibiotic on the gut microbiome. The study involved analyzing rectal swabs from individuals who used doxy-PEP and those who received standard-of-care treatment over a period of six months. While no major changes were observed in the gut bacterial community of doxy-PEP users, an increase in tetracycline resistance genes was noted over time, with a dose-dependent relationship – meaning the more doxy-PEP was used, the greater the increase in resistance genes.
Further research is needed to determine which gut bacteria are activating these tetracycline-resistant genes and whether this could lead to an increase in doxycycline-resistant infections among individuals taking doxy-PEP and in the broader community. Despite these concerns, the researchers believe that the benefits of using doxy-PEP currently outweigh the potential risks, especially in light of the increasing incidence of STIs, particularly syphilis, over the past decade. The study was funded by grants from the National Institutes of Health, the National Health, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases, among others.
