Signature changes in gut microbiome are associated with increased susceptibility to HIV-1 infection in MSM

Yue Chen,Shyamal Peddada,Matthew Mimiaga,Adam Fitch,Jeremy Martinson,Vatsala Rangachar Srinivas,Charles R Rinaldo,Huang Lin,Mariah Cole,Joseph Margolick,Heather Mckay,Barbara Methe,Alison Morris

doi:10.1186/s40168-021-01168-w

Abstract

BackgroundMen who have sex with men (MSM) have been disproportionately affected by HIV-1 since the beginning of the AIDS pandemic, particularly in the USA and Europe. Compared to men who have sex with women (MSW), MSM have a distinct fecal microbiome regardless of HIV-1 infection. However, it is unclear whether the MSM-associated gut microbiome affects the susceptibility and progression of HIV-1 infection. We studied fecal microbiome profiles, short-chain fatty acids, and blood plasma inflammatory cytokines of 109 HIV-1 seroconverters (SC) from the early, 1984–1985 phase of the HIV-1 pandemic in the Multicenter AIDS Cohort Study (MACS) before and after HIV-1 infection compared to 156 HIV-1-negative MACS MSM (negative controls [NC]).ResultsWe found that family Succinivibrionaceae, S24-7, Mogibacteriaceae, Coriobacteriaceae, and Erysipelotrichaceae were significantly higher (p<0.05), whereas Odoribacteraceae, Verucomicrobiaceae, Bacteroidaceae, Barnesiellaceae, and Rikenellaceae were significantly lower (p<0.05), in SC before HIV-1 infection compared to NC. At the species level, Prevotella stercorea, Eubacterium biforme, and Collinsella aerofaciens were significantly higher (p<0.05), and Eubacterium dolichum, Desulfovibrio D168, Alistipes onderdonkii, Ruminococcus torques, Bacteroides fragilis, Bacteroides caccae, Alistipes putredinis, Akkermansia muciniphila, Bacteroides uniformis, and Bacteroides ovatus were significantly lower (p<0.05) in SC before HIV-1 infection compared to NC. After HIV-1 infection, family Prevotellaceae and Victivallaceae and species Bacteroides fragilis and Eubacterium cylindroides were significantly higher (p<0.05) in SC who developed AIDS within 5 years compared to the SC who were AIDS free for more than 10 years without antiretroviral therapy (ART). In addition, family Victivallaceae and species Prevotella stercorea, Coprococcus eutactus, and Butyrivibrio crossotus were significantly higher (p<0.05) and Gemmiger formicilis and Blautia obeum were significantly lower (p<0.05) after HIV-1 infection in SC who developed AIDS within 5–10 years compared to the SC who were AIDS-free for more than 10 years without ART. Furthermore, plasma inflammatory cytokine levels of sCD14, sCD163, interleukin 6, and lipopolysaccharide binding protein were significantly higher in SC with p<0.05 before HIV-1 infection compared to NC.ConclusionsOur results suggest that pathogenic changes in the gut microbiome were present in MSM several months prior to infection with HIV-1 in the early phase of the AIDS pandemic in the USA. This was associated with increased inflammatory biomarkers in the blood and risk for development of AIDS.9QqqYi-nWWd_GoM3dpywa1Video abstract

Highlights

Men who have sex with men (MSM) have been disproportionately affected by Human immunodeficiency virus type 1 (HIV-1) since the beginning of the AIDS pandemic, in the USA and Europe
Our results suggest that pathogenic changes in the gut microbiome were present in MSM several months prior to infection with HIV-1 in the early phase of the AIDS pandemic in the USA
Stool specimens were obtained from Multicenter AIDS Cohort Study (MACS) participants beginning April 1, 1984, in order to investigate these specimens for potential viruses that caused AIDS

Summary

Introduction

Men who have sex with men (MSM) have been disproportionately affected by HIV-1 since the beginning of the AIDS pandemic, in the USA and Europe. Compared to men who have sex with women (MSW), MSM have a distinct fecal microbiome regardless of HIV-1 infection. It is unclear whether the MSM-associated gut microbiome affects the susceptibility and progression of HIV-1 infection. Regardless of the route of HIV-1 infection, the virus quickly moves to GALT and rapidly replicates in part due to the high level of residential activated CD4+ T cells. This results in a rapid and severe depletion of CD4+ T cells, immune activation, and gut microbiome dysbiosis. There is no information directly comparing the gut microbiome prior to and soon after HIV-1 infection

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