Sexual Behavior is Linked to Changes in Gut Microbiome and Systemic Inflammation That Lead to HIV-1 Infection in Men Who Have Sex with Men

Overview

Journal Commun Biol

Specialty Biology

Date 2024 Sep 14

PMID 39277660

Authors

Huang Lin

Yue Chen

Grace Abror-Lacks

Meaghan Price

Alison Morris

Jing Sun

Frank Palella

Kara W Chew

Todd T Brown

Charles R Rinaldo

Shyamal D Peddada

Affiliations

Soon will be listed here.

Abstract

Pathogenic changes in gut microbial composition precede the onset of HIV-1 infection in men who have sex with men (MSM). This process is associated with increased levels of systemic inflammatory biomarkers and risk for AIDS development. Using mediation analysis framework, in this report we link the effects of unprotected receptive intercourse among MSM prior to primary HIV-1 infection to higher levels of proinflammatory cytokines sCD14 and sCD163 in plasma and a significant decrease in the abundance of A. muciniphila, B. caccae, B. fragilis, B. uniformis, Bacteroides spp., Butyricimonas spp., and Odoribacter spp., and a potential increase in the abundance of Dehalobacterium spp. and Methanobrevibacter spp. in stools of MSM with the highest number of sexual partners. These differences in microbiota, together with a reduction in the pairwise correlations among commensal and short-chain fatty acid-producing bacteria with a number of sexual partners, support an increase in gut dysbiosis with the number of sexual partners. These results demonstrate the interconnectedness of sexual behavior, immune response, and microbiota composition, notably among MSM participating in high-risk sexual behaviors.

References

Mtshali A, Ngcapu S, Mindel A, Garrett N, Liebenberg L . HIV susceptibility in women: The roles of genital inflammation, sexually transmitted infections and the genital microbiome. J Reprod Immunol. 2021; 145:103291. DOI: 10.1016/j.jri.2021.103291. View

Siegel K, Caban M, Brown-Bradley C, Schrimshaw E . Condomless Anal Sex Between Male Sex Workers and Clients in the Age of Hookup Apps. AIDS Behav. 2023; 28(3):1077-1092. PMC: 11336491. DOI: 10.1007/s10461-023-04216-8. View

Peddada S, Lobenhofer E, Li L, Afshari C, Weinberg C, Umbach D . Gene selection and clustering for time-course and dose-response microarray experiments using order-restricted inference. Bioinformatics. 2003; 19(7):834-41. DOI: 10.1093/bioinformatics/btg093. View

Lin H, Eggesbo M, Peddada S . Linear and nonlinear correlation estimators unveil undescribed taxa interactions in microbiome data. Nat Commun. 2022; 13(1):4946. PMC: 9399263. DOI: 10.1038/s41467-022-32243-x. View

Kingsley L, Detels R, Kaslow R, Polk B, Rinaldo Jr C, CHMIEL J . Risk factors for seroconversion to human immunodeficiency virus among male homosexuals. Results from the Multicenter AIDS Cohort Study. Lancet. 1987; 1(8529):345-9. DOI: 10.1016/s0140-6736(87)91725-9. View

Tuddenham S, Koay W, Sears C . HIV, Sexual Orientation, and Gut Microbiome Interactions. Dig Dis Sci. 2020; 65(3):800-817. PMC: 7301749. DOI: 10.1007/s10620-020-06110-y. View

O Murchu E, Marshall L, Teljeur C, Harrington P, Hayes C, Moran P . Oral pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations. BMJ Open. 2022; 12(5):e048478. PMC: 9096492. DOI: 10.1136/bmjopen-2020-048478. View

Coleman S, Neff C, Li S, Armstrong A, Schneider J, Sen S . Can gut microbiota of men who have sex with men influence HIV transmission?. Gut Microbes. 2020; 11(3):610-619. PMC: 7524317. DOI: 10.1080/19490976.2019.1700756. View

Wang C, Hu J, Blaser M, Li H . Estimating and testing the microbial causal mediation effect with high-dimensional and compositional microbiome data. Bioinformatics. 2019; 36(2):347-355. PMC: 7867996. DOI: 10.1093/bioinformatics/btz565. View

10.

Kelley C, Pollack I, Yacoub R, Zhu Z, Van Doren V, Gumber S . Condomless receptive anal intercourse is associated with markers of mucosal inflammation in a cohort of men who have sex with men in Atlanta, Georgia. J Int AIDS Soc. 2021; 24(12):e25859. PMC: 8673926. DOI: 10.1002/jia2.25859. View

11.

Loeys T, Moerkerke B, De Smet O, Buysse A, Steen J, Vansteelandt S . Flexible Mediation Analysis in the Presence of Nonlinear Relations: Beyond the Mediation Formula. Multivariate Behav Res. 2016; 48(6):871-94. DOI: 10.1080/00273171.2013.832132. View

12.

Ackerley C, Smith S, Murray P, Amancha P, Arthur R, Zhu Z . The rectal mucosal immune environment and HIV susceptibility among young men who have sex with men. Front Immunol. 2022; 13:972170. PMC: 9631201. DOI: 10.3389/fimmu.2022.972170. View

13.

Lange T, Vansteelandt S, Bekaert M . A simple unified approach for estimating natural direct and indirect effects. Am J Epidemiol. 2012; 176(3):190-5. DOI: 10.1093/aje/kwr525. View

14.

Perler B, Reinhart E, Montgomery M, Maynard M, Shapiro J, Belenky P . Evaluation of the Microbiome in Men Taking Pre-exposure Prophylaxis for HIV Prevention. AIDS Behav. 2021; 25(7):2005-2013. PMC: 8169604. DOI: 10.1007/s10461-020-03130-7. View

15.

DSouza G, Bhondoekhan F, Benning L, Margolick J, Adedimeji A, Adimora A . Characteristics of the MACS/WIHS Combined Cohort Study: Opportunities for Research on Aging With HIV in the Longest US Observational Study of HIV. Am J Epidemiol. 2021; 190(8):1457-1475. PMC: 8484936. DOI: 10.1093/aje/kwab050. View

16.

Bragazzi N, Khamisy-Farah R, Tsigalou C, Mahroum N . HIV Pre-exposure Prophylaxis and Its Impact on the Gut Microbiome in Men Having Sex With Men. Front Microbiol. 2022; 13:922887. PMC: 9260425. DOI: 10.3389/fmicb.2022.922887. View

17.

Callahan B, McMurdie P, Rosen M, Han A, Johnson A, Holmes S . DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016; 13(7):581-3. PMC: 4927377. DOI: 10.1038/nmeth.3869. View

18.

Rodrigues V, Elias-Oliveira J, Pereira I, Pereira J, Barbosa S, Machado M . and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Front Immunol. 2022; 13:934695. PMC: 9300896. DOI: 10.3389/fimmu.2022.934695. View

19.

Chen Y, Lin H, Cole M, Morris A, Martinson J, McKay H . Signature changes in gut microbiome are associated with increased susceptibility to HIV-1 infection in MSM. Microbiome. 2021; 9(1):237. PMC: 8656045. DOI: 10.1186/s40168-021-01168-w. View

20.

Kabapy A, Shatat H, Abd El-Wahab E . Attributes of HIV infection over decades (1982-2018): A systematic review and meta-analysis. Transbound Emerg Dis. 2020; 67(6):2372-2388. DOI: 10.1111/tbed.13621. View