Evaluation of the Microbiome in Men Taking Pre-exposure Prophylaxis for HIV Prevention.


Journal

AIDS and behavior
ISSN: 1573-3254
Titre abrégé: AIDS Behav
Pays: United States
ID NLM: 9712133

Informations de publication

Date de publication:
Jul 2021
Historique:
accepted: 07 12 2020
pubmed: 5 1 2021
medline: 2 6 2021
entrez: 4 1 2021
Statut: ppublish

Résumé

Tenofovir-based regimens as pre-exposure prophylaxis (PrEP) are highly effective at preventing HIV infection. The most common side-effect is gastrointestinal (GI) distress which may be associated with changes in the microbiome. Dysbiosis of the microbiome can have numerous health-related consequences. To understand the effect of PrEP on dysbiosis, we evaluated 27 individuals; 14 were taking PrEP for an average of 171 weeks. Sequencing of 16S rRNA was performed using self-collected rectal swabs. Mixed beta diversity testing demonstrated significant differences between PrEP and non-PrEP users with Bray-Curtis and unweighted UniFrac analyses (p = 0.05 and 0.049, respectively). At the genus level, there was a significant reduction in Finegoldia, along with a significant increase in Catenibacterium and Prevotella in PrEP users. Prevotella has been associated with inflammatory pathways, insulin resistance and cardiovascular disease, while Catenibacterium has been associated with morbid obesity and metabolic syndrome. Overall, these results suggest that PrEP may be associated with some degree of microbiome dysbiosis, which may contribute to GI symptoms. Long-term impact of these changes is unknown. Los regímenes basados en tenofovir como profilaxis previa a la exposición (PPrE) son muy eficaces en prevenir la infección por VIH. El efecto secundario más común es el malestar gastrointestinal (GI) que puede estar asociado con cambios en el microbioma. La disbiosis del microbioma puede tener numerosas consecuencias relacionadas con la salud. Para comprender el efecto de la PPrE sobre la disbiosis, evaluamos a 27 individuos; 14 de los individuos tomaron PPrE durante un promedio de 171 semanas. La secuenciación del ARNr 16S se realizó utilizando hisopos rectales recolectados por los propios pacientes. Las pruebas beta de diversidad mixta demostraron diferencias significativas entre los usuarios de PPrE y los que no utilizaron PPrE al analizarlos mediente Bray–Curtis y UniFrac no ponderados (p = 0,05 y 0,049, respectivamente). A nivel de género, hubo una reducción significativa de Finegoldia, junto con un aumento significativo de Catenibacterium y Prevotella en usuarios de PPrE. Prevotella se ha asociado con trayectorias inflamatorias, resistencia a insulina y enfermedades cardiovasculares, mientras que Catenibacterium se ha asociado con enfermedades como obesidad mórbida y padecimientos de síndrome metabólico. En general, estos resultados sugieren que la PPrE puede estar asociada con cierto grado de disbiosis del microbioma, lo que puede contribuir a los síntomas gastrointestinales. El impacto a largo plazo de estos cambios se desconoce.

Autres résumés

Type: Publisher (spa)
Los regímenes basados en tenofovir como profilaxis previa a la exposición (PPrE) son muy eficaces en prevenir la infección por VIH. El efecto secundario más común es el malestar gastrointestinal (GI) que puede estar asociado con cambios en el microbioma. La disbiosis del microbioma puede tener numerosas consecuencias relacionadas con la salud. Para comprender el efecto de la PPrE sobre la disbiosis, evaluamos a 27 individuos; 14 de los individuos tomaron PPrE durante un promedio de 171 semanas. La secuenciación del ARNr 16S se realizó utilizando hisopos rectales recolectados por los propios pacientes. Las pruebas beta de diversidad mixta demostraron diferencias significativas entre los usuarios de PPrE y los que no utilizaron PPrE al analizarlos mediente Bray–Curtis y UniFrac no ponderados (p = 0,05 y 0,049, respectivamente). A nivel de género, hubo una reducción significativa de Finegoldia, junto con un aumento significativo de Catenibacterium y Prevotella en usuarios de PPrE. Prevotella se ha asociado con trayectorias inflamatorias, resistencia a insulina y enfermedades cardiovasculares, mientras que Catenibacterium se ha asociado con enfermedades como obesidad mórbida y padecimientos de síndrome metabólico. En general, estos resultados sugieren que la PPrE puede estar asociada con cierto grado de disbiosis del microbioma, lo que puede contribuir a los síntomas gastrointestinales. El impacto a largo plazo de estos cambios se desconoce.

Identifiants

pubmed: 33394167
doi: 10.1007/s10461-020-03130-7
pii: 10.1007/s10461-020-03130-7
pmc: PMC8169604
mid: NIHMS1694271
doi:

Substances chimiques

Anti-HIV Agents 0
RNA, Ribosomal, 16S 0
Emtricitabine G70B4ETF4S

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2005-2013

Subventions

Organisme : NCCIH NIH HHS
ID : R21AT010366
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK125382
Pays : United States
Organisme : NIMH NIH HHS
ID : R25 MH083620
Pays : United States
Organisme : NCCIH NIH HHS
ID : R21 AT010366
Pays : United States
Organisme : U.S. Department of Defense
ID : W81XWH-18-1-0198
Organisme : Brown University
ID : P20GM121344
Organisme : NIGMS NIH HHS
ID : P20 GM121344
Pays : United States

Références

Maartens G, Celum C, Lewin S. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet. 2014;384(9939):19–25.
doi: 10.1016/S0140-6736(14)60164-1
Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587–99.
doi: 10.1056/NEJMoa1011205
Solomon MM, Lama JR, Glidden DV. Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis. AIDS. 2014;28(6):851–9.
doi: 10.1097/QAD.0000000000000156
Gandhi M, Glidden DV, Mayer K, et al. Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study. Lancet HIV. 2016;3(11):e521–8.
doi: 10.1016/S2352-3018(16)30153-9
Mulligan K, Glidden DV, Anderson PL, et al. Effects of emtricitabine/tenofovir on bone mineral density in HIV-negative persons in a randomized, double-blind, Placebo-Controlled Trial. Clin Infect Dis. 2015;61(4):572–80.
doi: 10.1093/cid/civ324
Villanueva- MJ, Perez-Matute P, Recio-Fernandez E, Lezana Rosales JM, Oteo JA. Differential effects of antiretrovirals on microbial translocation and gut microbiota composition of HIV-infected patients. J Int AIDS Soc. 2017;20(1):21526.
doi: 10.7448/IAS.20.1.21526
Klatt NR, Funderburg NT, Brenchley JM. Microbial translocation, immune activation, and HIV disease. Trends Microbiol. 2013;21:6–13.
doi: 10.1016/j.tim.2012.09.001
Zevin AS, McKinnon L, Burgener A, Klatt NR. Microbial translocation and microbiome dysbiosis in HIV-associated immune activation. Curr Opin HIV AIDS. 2016;11:182–90.
doi: 10.1097/COH.0000000000000234
Gootenberg DB, Paer JM, Luevano JM, et al. HIV-associated changes in the enteric microbial community: potential role in loss of homeostasis and development of systemic inflammation. Curr Opin Infect Dis. 2017;30(1):31–43.
doi: 10.1097/QCO.0000000000000341
Dubé MP, Park SY, Ross H, et al. Daily HIV pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine reduced Streptococcus and increased Erysipelotrichaceae in rectal microbiota. Sci Rep. 2018;8(1):15212.
doi: 10.1038/s41598-018-33524-6
Fulcher JA, Li F, Cook RR, et al. Rectal microbiome alterations associated with oral human immunodeficiency virus pre-exposure prophylaxis. Open Forum Infect Dis. 2019;6(11):ofz463.
doi: 10.1093/ofid/ofz463
Noguera-Julian M, Rocafort M, Guillen Y, et al. Gut microbiota linked to sexual preference and HIV infection. EBioMedicine. 2016;5:135–46.
doi: 10.1016/j.ebiom.2016.01.032
Kelley CF, Kraft CS, de Man TJB, et al. The rectal mucosa and condomless receptive anal intercourse in HIV negative MSM: implications for hiv transmission and prevention. Mucosal Immunol. 2017;10(4):996–1007.
doi: 10.1038/mi.2016.97
Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–80.
doi: 10.1038/nature09944
Schincaglia GP, Hong BY, Rosania A, et al. Clinical, immune, and microbiome traits of gingivitis and peri-implant mucositis. J Dent Res. 2017;96(1):47–55.
doi: 10.1177/0022034516668847
Scher JU, Ubeda C, Equinda M, et al. Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum. 2012;64(10):3083–94.
doi: 10.1002/art.34539
Moreno-Indias I, Sanchez-Alcoholado L, Garcia-Fuentes E, et al. Insulin resistance is associated with specific gut microbiota in appendix samples from morbidly obese patients. Am J Transl Res. 2016;8(12):5672–84.
pubmed: 28078038 pmcid: 5209518
Mugwanya KK, Baeten JM. Safety of oral tenofovir disoproxil fumarate-based pre-exposure prophylaxis for HIV prevention. Expert Opin Drug Saf. 2017;15(2):265–73.
doi: 10.1517/14740338.2016.1128412
Petersen C, Round JL. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol. 2014;16(7):1024–33.
doi: 10.1111/cmi.12308
Binda C, Lopetuso LR, Rizzatti G, et al. Actinobacteria: a relevant minority for the maintenance of gut homeostasis. Dig Liver Dis. 2018;50(5):421–8.
doi: 10.1016/j.dld.2018.02.012
Budding AE, Grasman ME, Eck A, et al. Rectal swabs for analysis of the intestinal microbiota. PLoS ONE. 2014;9(7):e101344.
doi: 10.1371/journal.pone.0101344
Biehl LM, Garzettia D, Farowski F, et al. Usability of rectal swabs for microbiome sampling in cohort study of hematological and oncological patients. PLoS ONE. 2019;14(4):e0215428.
doi: 10.1371/journal.pone.0215428
Caporaso JG, Kuczynski J, Stombaugh J, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7:335–6.
doi: 10.1038/nmeth.f.303
Caporaso JG, Lauber CL, Walters WA, et al. Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. ISME J. 2012;6(8):1621–4.
doi: 10.1038/ismej.2012.8
Walters W, Hyde ER, Berg-Lyons D, et al. Improved bacterial 16S rRNA gene (V4 and V4–5) and fungal internal transcribed spacer marker gene primers for microbial community surveys. mSystems. 2016;1(1):e00009-e00015.
doi: 10.1128/mSystems.00009-15
Thompson LR, Sanders JG, McDonald D, et al. A communal catalogue reveals Earth’s multiscale microbial diversity. Nature. 2017;551(7681):457–63.
doi: 10.1038/nature24621
Callahan BJ, McMuride PJ, Rosen MJ, et al. DADA2: high resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581–3.
doi: 10.1038/nmeth.3869
Gurevich A, Saveliev V, Vyahhi N, et al. QUAST: quality assessment tool for genome assemblies. Bioinformatics. 2013;29(8):1072–5.
doi: 10.1093/bioinformatics/btt086
Segata N, Izard J, Waldron L, et al. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6):R60.
doi: 10.1186/gb-2011-12-6-r60
Hassan A, Blumenthal JS, Dube MP, et al. Effect of rectal douching/enema on rectal gonorrhoea and chlamydia among a cohort of men who have sex with men on HIV Pre-exposure prophylaxis. Sex Transm Infect. 2018;94(7):508–14.
doi: 10.1136/sextrans-2017-053484
Haaland RE, Fountain J, Hu Y, et al. Repeated rectal application of a hyperosmolar lubricant is associated with microbiota shifts but does not affect PrEP drug concentrations: results from a randomized trial in men who have sex with men. J Int AIDS Soc. 2018;21(10):e25199.
doi: 10.1002/jia2.25199
Zhernakova A, Kurilshikov A, Bonder MJ, et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science. 2016;352(6285):565–9.
doi: 10.1126/science.aad3369
Armstrong AJS, Shaffer M, Nusbacher NM, et al. An exploration of Prevotella-rich microbiomes in HIV and men who have sex with men. Microbiome. 2018;6:198.
doi: 10.1186/s40168-018-0580-7
Gallardo-Becerra L, Cornejo-Granados F, Lopez-Garcia R, et al. Metatranscriptomic analysis to define the Secrebiome, and 16S rRNA profiling of the gut microbiome in obesity and metabolic syndrome of Mexican children. Microb Cell Fact. 2020;19:61.
doi: 10.1186/s12934-020-01319-y
Carda-dieguez M, Cardenas N, Aparicio M, et al. Variations in vaginal, penile, and oral microbiota after sexual intercourse: a case report. Front Med (Lausanne). 2019;6:178.
doi: 10.3389/fmed.2019.00178
Price LB, Liu CM, Johnson KE, et al. The effects of circumcision on the penis microbiome. PLoS ONE. 2010;5(1):e8422.
doi: 10.1371/journal.pone.0008422
Liu CM, Prodger JL, Tobian AAR, et al. Penile anaerobic dysbiosis as a risk factor for HIV infection. mBio. 2017;4:e00996-e1017.
Flygel TT, Sovershaeva E, Claassen-Weitz S, et al. Composition of gut microbiota of children and adolescents with perinatal human immunodeficiency virus infection taking antiretroviral therapy in zimbabwe. J Infect Dis. 2020;221(3):483–92.
pubmed: 31549151
Nowak RG, Bentzen SM, Ravel J, et al. Rectal microbiota among HIV-uninfected, untreated HIV, and treated HIV-infected men who have sex with men (MSM) in Nigeria. AIDS. 2017;31(6):857–62.
doi: 10.1097/QAD.0000000000001409

Auteurs

Bryce K Perler (BK)

Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA. bryce.perler@gmail.com.

Elizabeth M Reinhart (EM)

Department of Molecular Microbiology and Immunology, Brown University, Providence, USA.

Madeline Montgomery (M)

Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, USA.

Michaela Maynard (M)

Division of Infectious Diseases, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, USA.

Jason M Shapiro (JM)

Division of Pediatric Gastroenterology, Nutrition and Liver Diseases, Warren Alpert Medical School of Brown University, Providence, USA.

Peter Belenky (P)

Department of Molecular Microbiology and Immunology, Brown University, Providence, USA. Peter_Belenky@brown.edu.

Philip A Chan (PA)

Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, USA.
Division of Infectious Diseases, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, USA.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH