Impact of using doxy-PEP on the intestinal resistome for DNA and RNA sequencing samples. A–dNormalized resistance mass (A,b) and the alpha diversity of the resistome (Shannon diversity index) (c,d) for DP versus SOC participants (DNA-seq: n = 127; RNA sequence: n = 86). e,fBeta diversity of the resistome (Bray-Curtis index) in PD versus SOC participants at 6 months (DNA-seq: n = 69; RNA sequence: n= 60). P. values were calculated using the two-tailed Wilcoxon rank sum test and adjusted for multiple comparisons (A–d). Double-sided PERMANOVA P.beta diversity values were calculated and adjusted for multiple comparisons (e,f). Box plot elements include a center line (median), box boundaries (upper and lower quartiles), and whiskers (1.5 × IQR). Credit: Natural medicine(2024). DOI: 10.1038/s41591-024-03274-2
Taking a dose of the oral antibiotic doxycycline after high-risk sex has significantly reduced the incidence of sexually transmitted infections (STIs) in places where this strategy is being tested.
Despite its effectiveness, the new strategy, known as doxy-PEP, can carry risks, particularly with chronic use. Experts are concerned about the impact on the gut bacteria community, also called the microbiome, and the possibility that the antibiotic will give rise to resistant bacterial strains.
Now, using metagenomic sequencing to see the impact of doxycycline on the gut microbiome of those who took it frequently for six months, UC San Francisco researchers have found both a sense of comfort and a possible source of concern.
Doxy-PEP did not have much impact on the overall composition of bacterial communities in the gastrointestinal tract. But scientists have noted signs of developing resistance to tetracycline, the class of antibiotics to which doxycycline belongs, which could make it less effective.
The study appears in Natural medicine.
“Although doxy-PEP does not appear to have an overall impact on the gut microbiome, it did impact the antimicrobial resistance of gut bacteria, both in terms of the proportion of tetracycline class resistance genes and the amount activated or expressed,” said Chaz Langelier, MD, Ph.D., associate professor of medicine in the Division of Infectious Diseases at UCSF and senior author of the paper. “So it’s not totally trivial.”
San Francisco’s high-profile role in STI prevention
Doxy-PEP is short for doxycycline post-exposure prophylaxis and involves taking two 100-milligram tablets within 72 hours of having sex without a condom.
Driven by promising early clinical trial results, San Francisco became the first city in the country in October 2022 to recommend doxy-PEP to gay and bisexual men and transgender women with a history of unprotected encounters with multiple partners.
In March 2024, the San Francisco Department of Public Health released results showing that after about a year, this approach had reduced the incidence of chlamydia and early syphilis in half. In June, the U.S. Centers for Disease Control and Prevention (CDC) released guidelines recommending doxy-PEP for these groups. This is the first new STI prevention tool to be adopted in decades.
But the widespread use of antibiotics raises concerns about resistance and their potentially harmful impact on gut health, particularly the balance of bacteria and other microbes. Disturbance can cause diarrhea, nausea, fever and abdominal pain; and until now, research into these side effects has been very limited.
In collaboration with the Chan Zuckerberg Biohub and scientists in Washington and Georgia, UCSF researchers studied participants from the recent doxy-PEP clinical trial in San Francisco and Seattle, led by Annie Luetkemeyer, MD, professor of medicine at the UCSF Division of Infectious Diseases. .
The study included 100 people who used doxy-PEP and 50 people who received standard care and did not use doxy-PEP. The researchers analyzed rectal swabs taken at enrollment and after six months to study the presence of DNA and RNA of gut bacteria and their antibiotic resistance genes.
“Although we found no major changes in the gut bacteria community among doxy-PEP users, we did see that over time, doxy-PEP users had increasing amounts of resistance genes to tetracycline in their gut,” said Victoria T. Chu, MD, MPH. , assistant professor of pediatrics in the UCSF Division of Global Health and Infectious Diseases and first author of the study. “It also seemed to be dose-dependent, meaning the more doxy-PEP they used, the greater the increase.”
Further research is needed to determine which gut bacteria activate these tetracycline-resistant genes to know whether this will lead to more doxycycline-resistant infections in individuals taking doxy-PEP and in the community as a whole.
“Right now it seems like the pros outweigh the cons,” Langelier said. “Especially given the dramatic increase in STIs, particularly syphilis, over the past decade.”
More information:
Victoria T. Chu et al, Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome, Natural medicine(2024). DOI: 10.1038/s41591-024-03274-2
Provided by University of California, San Francisco
Quote: How doxycycline for STI prevention affects the gut microbiome (October 3, 2024) retrieved October 3, 2024 from
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