Significant associations between high-risk sexual behaviors and enterotypes of gut microbiome in HIV-negative men who have sex with men

ABSTRACT Gut microbiome of men who have sex with men (MSM) exhibits distinctive characteristics compared with general populations. The dysbiosis of the gut microbiome in MSM is also associated with the onset and evolution of HIV infection. Enterotype is an important feature of the gut microbiome and...

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Main Authors: Kangjie Li, Xinjing Liu, Xiaohua Zhong, Haijiao Zeng, Tian Liu, Bing Lin, Pinyi Chen, Biao Xie, Xiaoni Zhong
Format: Article
Language:English
Published: American Society for Microbiology 2025-07-01
Series:mSphere
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Online Access:https://journals.asm.org/doi/10.1128/msphere.00232-25
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author Kangjie Li
Xinjing Liu
Xiaohua Zhong
Haijiao Zeng
Tian Liu
Bing Lin
Pinyi Chen
Biao Xie
Xiaoni Zhong
author_facet Kangjie Li
Xinjing Liu
Xiaohua Zhong
Haijiao Zeng
Tian Liu
Bing Lin
Pinyi Chen
Biao Xie
Xiaoni Zhong
author_sort Kangjie Li
collection DOAJ
description ABSTRACT Gut microbiome of men who have sex with men (MSM) exhibits distinctive characteristics compared with general populations. The dysbiosis of the gut microbiome in MSM is also associated with the onset and evolution of HIV infection. Enterotype is an important feature of the gut microbiome and remains unaffected by demographic factors. However, the enterotypes of gut microbiome in MSM are unclear. The associations between enterotypes and high-risk sexual behaviors in this population also remain to be elucidated. HIV-negative MSM were recruited in this study. Fecal samples of the participants were collected and subjected to 16S rRNA gene sequencing. Enterotype clusters were determined by Jensen-Shannon divergence based on genus-level relative abundance. Microbial function predictions were conducted by PICRUSt2 software. Univariate and multivariate logistic regression approaches were utilized to analyze the associations of enterotypes with sexual behaviors. A three-category random forest machine learning model was performed to further examine the correlation between abundant microbiome in each enterotype cluster and anal sex roles. Two enterotype clusters were identified in our data sets, primarily driven by genera Phocaeicola and Segatella. The alpha diversity was comparable between the two enterotype clusters. Microbial metabolic functions significantly differed, and multivariate logistic regression indicated a significant association between anal sex role and enterotype. The results of the three-category random forest model indicate that the dominant bacterial communities in gut enterotypes can effectively differentiate MSM who engage exclusively in receptive anal intercourse from those who engage in insertive or versatile anal intercourse (AUC: 0.6400, 0.6929, respectively). We identified two enterotype clusters of gut microbiome in HIV-negative MSM. Enterotypes of MSM were significantly associated with anal sex roles. These findings further highlight the close correlation between the gut microbiome and anal intercourse roles.IMPORTANCEOur study’s discovery that gut microbiome enterotypes are significantly associated with anal sex roles in HIV-negative MSM opens a new frontier in understanding the complex interplay between microbiology and sexual health. This finding underscores the urgency of delving into the mechanistic connections between the gut microbiome, sexual behaviors, and HIV infection. By identifying modifiable factors influencing gut microbiome composition, we have paved the way for developing personalized preventive strategies that could disrupt the transmission dynamics of HIV within this high-risk population. This research contributes to the fundamental understanding of the gut microbiome’s role in the sexual health of MSM, making it a pivotal advancement in the fields of gut microbiome research and sexual health.
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spelling doaj-art-baa44f4c1c794274b675c6e12e645d902025-08-20T03:09:21ZengAmerican Society for MicrobiologymSphere2379-50422025-07-0110710.1128/msphere.00232-25Significant associations between high-risk sexual behaviors and enterotypes of gut microbiome in HIV-negative men who have sex with menKangjie Li0Xinjing Liu1Xiaohua Zhong2Haijiao Zeng3Tian Liu4Bing Lin5Pinyi Chen6Biao Xie7Xiaoni Zhong8School of Public Health, Research Center for Medicine and Social Development, Chongqing Medical University, Chongqing, ChinaSchool of Public Health, Research Center for Medicine and Social Development, Chongqing Medical University, Chongqing, ChinaHospital of Sichuan International Studies University, Chongqing, ChinaSchool of Public Health, Research Center for Medicine and Social Development, Chongqing Medical University, Chongqing, ChinaSchool of Public Health, Research Center for Medicine and Social Development, Chongqing Medical University, Chongqing, ChinaSchool of Public Health, Research Center for Medicine and Social Development, Chongqing Medical University, Chongqing, ChinaChongqing Medical University, Chongqing, Chongqing, ChinaSchool of Public Health, Research Center for Medicine and Social Development, Chongqing Medical University, Chongqing, ChinaSchool of Public Health, Research Center for Medicine and Social Development, Chongqing Medical University, Chongqing, ChinaABSTRACT Gut microbiome of men who have sex with men (MSM) exhibits distinctive characteristics compared with general populations. The dysbiosis of the gut microbiome in MSM is also associated with the onset and evolution of HIV infection. Enterotype is an important feature of the gut microbiome and remains unaffected by demographic factors. However, the enterotypes of gut microbiome in MSM are unclear. The associations between enterotypes and high-risk sexual behaviors in this population also remain to be elucidated. HIV-negative MSM were recruited in this study. Fecal samples of the participants were collected and subjected to 16S rRNA gene sequencing. Enterotype clusters were determined by Jensen-Shannon divergence based on genus-level relative abundance. Microbial function predictions were conducted by PICRUSt2 software. Univariate and multivariate logistic regression approaches were utilized to analyze the associations of enterotypes with sexual behaviors. A three-category random forest machine learning model was performed to further examine the correlation between abundant microbiome in each enterotype cluster and anal sex roles. Two enterotype clusters were identified in our data sets, primarily driven by genera Phocaeicola and Segatella. The alpha diversity was comparable between the two enterotype clusters. Microbial metabolic functions significantly differed, and multivariate logistic regression indicated a significant association between anal sex role and enterotype. The results of the three-category random forest model indicate that the dominant bacterial communities in gut enterotypes can effectively differentiate MSM who engage exclusively in receptive anal intercourse from those who engage in insertive or versatile anal intercourse (AUC: 0.6400, 0.6929, respectively). We identified two enterotype clusters of gut microbiome in HIV-negative MSM. Enterotypes of MSM were significantly associated with anal sex roles. These findings further highlight the close correlation between the gut microbiome and anal intercourse roles.IMPORTANCEOur study’s discovery that gut microbiome enterotypes are significantly associated with anal sex roles in HIV-negative MSM opens a new frontier in understanding the complex interplay between microbiology and sexual health. This finding underscores the urgency of delving into the mechanistic connections between the gut microbiome, sexual behaviors, and HIV infection. By identifying modifiable factors influencing gut microbiome composition, we have paved the way for developing personalized preventive strategies that could disrupt the transmission dynamics of HIV within this high-risk population. This research contributes to the fundamental understanding of the gut microbiome’s role in the sexual health of MSM, making it a pivotal advancement in the fields of gut microbiome research and sexual health.https://journals.asm.org/doi/10.1128/msphere.00232-25MSMgut microbiomeenterotyperandom forest machine learning
spellingShingle Kangjie Li
Xinjing Liu
Xiaohua Zhong
Haijiao Zeng
Tian Liu
Bing Lin
Pinyi Chen
Biao Xie
Xiaoni Zhong
Significant associations between high-risk sexual behaviors and enterotypes of gut microbiome in HIV-negative men who have sex with men
mSphere
MSM
gut microbiome
enterotype
random forest machine learning
title Significant associations between high-risk sexual behaviors and enterotypes of gut microbiome in HIV-negative men who have sex with men
title_full Significant associations between high-risk sexual behaviors and enterotypes of gut microbiome in HIV-negative men who have sex with men
title_fullStr Significant associations between high-risk sexual behaviors and enterotypes of gut microbiome in HIV-negative men who have sex with men
title_full_unstemmed Significant associations between high-risk sexual behaviors and enterotypes of gut microbiome in HIV-negative men who have sex with men
title_short Significant associations between high-risk sexual behaviors and enterotypes of gut microbiome in HIV-negative men who have sex with men
title_sort significant associations between high risk sexual behaviors and enterotypes of gut microbiome in hiv negative men who have sex with men
topic MSM
gut microbiome
enterotype
random forest machine learning
url https://journals.asm.org/doi/10.1128/msphere.00232-25
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