Characterization Of The Gut Microbiota In Men Who Have Sex With Men With HIV Infection

Objective:Human immunodeficiency virus（HIV）infection is closely related to the changes in the composition and function of gut microbiota.Previous studies revealed that there was a significant gut microbial dysbiosis in people with HIV infection,and effective antiretroviral therapy（ART）can not restore it to a healthy state.However,it is not clear whether MSM-associated gut microbiome affects the susceptibility of HIV infection,and the effects of HIV and ART on gut microbiota after infection.In this study,we profiled the fecal microbiota by 16S ribosomal DNA（16S r DNA）sequencing in HIV-uninfected MSM,recent HIV infection MSM,ART-treated HIV-infected MSM and HIV-uninfected non-MSM.The aim of this study was to:（1）Understand the difference of gut microbioal structure and composition between HIV-uninfected MSM and HIV-uninfected non-MSM;（2）Explore the changes of gut microbiota in the early stage after HIV infection and the effect of ART on gut microbiota;（3）Further explore the correlation between gut microbiota and markers of microbial translocation and inflammatory cytokine.Methods:A cross-sectional study was conducted to recruit 30 HIV-uninfected MSM,30recent HIV infection MSM,30 ART-treated HIV-infected MSM who were consulted and tested in Anhui Qingwei Health Service Center from January 2021 to June 2021.At the same time,30 HIV-uninfected non-MSM controls were matched according to sex and age.The demographic characteristics of the participants were collected by questionnaire,and fecal and blood samples were collected at the same time.The gut microbiota of all participants were detected by 16S r DNA sequencing technology,and the composition and diversity of gut microbiota among different groups were analyzed.Plasma levels of markers of microbial translocation（s CD14 and LBP）and systemic inflammation（CRP）were measured using a Luminex Human Discovery Assay.Results:（1）The median age of 120 participants was 25（23,28）years old,and the BMI was（22.26±2.28）kg/m~2.The education level was mainly college or above（84.17%）,and the occupation were mainly students and company employees/government staff（79.17%）.（2）There were no significant difference inαandβdiversity between HIV-uninfected MSM and HIV-uninfected non-MSM,but there were some differences in the composition of gut microbiota.The average relative abundance of Bacteroides,Prevotella and Alloprevotella in HIV-uninfected MSM group was higher,while Firmicutes,Bacteroides and Faecalibacterium were lower.（3）Theαdiversity of gut microbiota in ART-treated HIV-infected MSM group was significantly lower than that in recent HIV infection MSM group and HIV-uninfected MSM group,and the three groups was showed as HIV-uninfected MSM group>recent HIV infection MSM group>ART-treated HIV-infected MSM group.The results of PCo A showed that there were significant differences inβdiversity between ART-treated HIV-infected MSM group and recent HIV infection MSM group and HIV-uninfected MSM group,but there was no statistical difference between the latter two groups.At the phylum level,the average relative abundance of Fusobacteria and Actinobacteria was significantly different among the three groups,in which Fusobacteria was significantly enriched in ART-treated HIV-infected MSM group and Actinobacteria in recent HIV infection MSM group;at the genus level,the relative abundance of Fusobacterium and Megasphaera increased significantly in ART-treated HIV-infected MSM group,while the relative abundance of Faecalibacterium and Roseburia decreased significantly.In addition,the effects of different ART regimens on the gut microbiota of HIV-infected MSM showed that the NNRTI-based treatment could resulted in significant changes in the diversity and composition of gut microbiota when compared with untreated HIV-infected MSM.（4）The results of random forest model analysis showed that five operational taxonomic units（OTUs）were identified to distinguish gut microbes in recent HIV infection MSM group and HIV-uninfected MSM group,with areas under the receiver operating curve（AUC）was 76.24%（95%CI:61.17%-91.31%）.（5）s CD14 and CRP showed a trend of HIV-uninfected MSM group>recent HIV infection MSM group>ART-treated HIV-infected MSM group among the three groups.The results of correlation analysis showed that there were no significant correlation betweenαdiversity index and markers of microbial translocation and inflammatory cytokines,but a significant negative correlation betweenαdiversity index and Fusobacterium was found.There was a significant negative correlation between s CD14 and the genus of Faecalibacterium（r_s=-0.259,P=0.014）.Conclusions:（1）The diversity of gut microbiota in HIV-uninfected MSM was similar to that of HIV-uninfected non-MSM,but in terms of specific bacterial composition,the micorbiota has shifted to a model that is more susceptible to disease;（2）In MSM,a slight gut bacterial dysbiosis occurred in a short time after HIV infection,and the gut dysbiosis is further aggravated after a period of ART,indicating that HIV and ART may have a superposition effect on gut dysbiosis;（3）In different ART regimens,NNRTI-based regimens may cause significant changes in the composition and diversity of gut microbita,suggesting that NNRTI drugs may have a direct effect on the gut microbiota.