Impact of doxycycline pre-exposure prophylaxis (doxyPrEP) for sexually transmitted infections on the microbiome of men who have sex with men on HIV PrEP

Abstract 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...

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Main Authors: Samantha Knodel, Leighanne Main, Marlon DeLeon, Alana Lamont, Joshua Edward, Amit K. Gupta, Laura Noel-Romas, Saira Mohammed, Tessa Tattersall, Jason Wong, Mark Hull, Troy Grennan, Adam D. Burgener
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61426-5
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author Samantha Knodel
Leighanne Main
Marlon DeLeon
Alana Lamont
Joshua Edward
Amit K. Gupta
Laura Noel-Romas
Saira Mohammed
Tessa Tattersall
Jason Wong
Mark Hull
Troy Grennan
Adam D. Burgener
author_facet Samantha Knodel
Leighanne Main
Marlon DeLeon
Alana Lamont
Joshua Edward
Amit K. Gupta
Laura Noel-Romas
Saira Mohammed
Tessa Tattersall
Jason Wong
Mark Hull
Troy Grennan
Adam D. Burgener
author_sort Samantha Knodel
collection DOAJ
description Abstract 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.
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spelling doaj-art-dfc4e58f497b43d9a6937ca525d52adb2025-08-20T04:01:36ZengNature PortfolioNature Communications2041-17232025-07-0116111010.1038/s41467-025-61426-5Impact of doxycycline pre-exposure prophylaxis (doxyPrEP) for sexually transmitted infections on the microbiome of men who have sex with men on HIV PrEPSamantha Knodel0Leighanne Main1Marlon DeLeon2Alana Lamont3Joshua Edward4Amit K. Gupta5Laura Noel-Romas6Saira Mohammed7Tessa Tattersall8Jason Wong9Mark Hull10Troy Grennan11Adam D. Burgener12Center for Global Health and Diseases, Department of Pathology, Case Western Reserve UniversityCenter for Global Health and Diseases, Department of Pathology, Case Western Reserve UniversityMax Rady College of Medicine, Rady Faculty of Health Sciences, University of ManitobaDepartment of Biochemistry and Medical Genetics, University of ManitobaBC Centre for Disease ControlBC Centre for Disease ControlMax Rady College of Medicine, Rady Faculty of Health Sciences, University of ManitobaBC Centre for Disease ControlBC Centre for Disease ControlBC Centre for Disease ControlBC Centre for Excellence in HIV/AIDSBC Centre for Excellence in HIV/AIDSCenter for Global Health and Diseases, Department of Pathology, Case Western Reserve UniversityAbstract 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.https://doi.org/10.1038/s41467-025-61426-5
spellingShingle Samantha Knodel
Leighanne Main
Marlon DeLeon
Alana Lamont
Joshua Edward
Amit K. Gupta
Laura Noel-Romas
Saira Mohammed
Tessa Tattersall
Jason Wong
Mark Hull
Troy Grennan
Adam D. Burgener
Impact of doxycycline pre-exposure prophylaxis (doxyPrEP) for sexually transmitted infections on the microbiome of men who have sex with men on HIV PrEP
Nature Communications
title Impact of doxycycline pre-exposure prophylaxis (doxyPrEP) for sexually transmitted infections on the microbiome of men who have sex with men on HIV PrEP
title_full Impact of doxycycline pre-exposure prophylaxis (doxyPrEP) for sexually transmitted infections on the microbiome of men who have sex with men on HIV PrEP
title_fullStr Impact of doxycycline pre-exposure prophylaxis (doxyPrEP) for sexually transmitted infections on the microbiome of men who have sex with men on HIV PrEP
title_full_unstemmed Impact of doxycycline pre-exposure prophylaxis (doxyPrEP) for sexually transmitted infections on the microbiome of men who have sex with men on HIV PrEP
title_short Impact of doxycycline pre-exposure prophylaxis (doxyPrEP) for sexually transmitted infections on the microbiome of men who have sex with men on HIV PrEP
title_sort impact of doxycycline pre exposure prophylaxis doxyprep for sexually transmitted infections on the microbiome of men who have sex with men on hiv prep
url https://doi.org/10.1038/s41467-025-61426-5
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