San Francisco became the first U.S. city to recommend doxycycline post-exposure prophylaxis (doxy-PEP) in October 2022 for gay and bisexual men and transgender women with a history of unprotected sex.

Doxy-PEP has significantly reduced the incidence of sexually transmitted infections (STIs) in areas where it is implemented, particularly halving the rates of chlamydia and early syphilis in San Francisco by March 2024.

Following the success in San Francisco, the CDC issued guidelines in June 2024, marking doxy-PEP as the first new STI prevention tool in decades.

A study conducted by UC San Francisco utilized metagenomic sequencing to assess the effects of doxy-PEP on the gut microbiome of frequent users over six months.

The study involved 100 participants using doxy-PEP and 50 controls, analyzing rectal swabs for gut bacteria and resistance genes.

While the study found no significant changes to the overall composition of gut bacteria, it indicated a dose-dependent increase in tetracycline resistance genes among doxy-PEP users.

Chaz Langelier, MD, Ph.D., noted that although doxy-PEP has limited global effects on gut bacteria, it does influence antimicrobial resistance.

Further research is necessary to identify which gut bacteria are activating tetracycline-resistant genes and to understand the implications for doxycycline-resistant infections in the community.

Despite its effectiveness, concerns remain about the long-term use of doxy-PEP, particularly regarding its impact on gut microbiome health and the potential for antibiotic resistance.

Experts suggest that the benefits of doxy-PEP currently outweigh the potential risks, especially in light of rising STI rates, particularly syphilis, over the past decade.

Concerns also persist about the potential side effects of antibiotics on gut health, which can include disruptions leading to diarrhea, nausea, and abdominal pain.

The findings of the study were published on October 3 in the journal Nature Medicine, highlighting the complexity of doxy-PEP's effects.