TY - JOUR
T1 - Signature changes in gut microbiome are associated with increased susceptibility to HIV-1 infection in MSM
AU - Chen, Yue
AU - Lin, Huang
AU - Cole, Mariah
AU - Morris, Alison
AU - Martinson, Jeremy
AU - Mckay, Heather
AU - Mimiaga, Matthew
AU - Margolick, Joseph
AU - Fitch, Adam
AU - Methe, Barbara
AU - Srinivas, Vatsala Rangachar
AU - Peddada, Shyamal
AU - Rinaldo, Charles R.
N1 - Funding Information:
This work was supported by N01-AI-32513, U01-HL-146208, and NIHS10OD023402 from the National Institutes of Health.
Funding Information:
Data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS), now the MACS/WIHS Combined Cohort Study (MWCCS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MACS Principal Investigators: Johns Hopkins University, Baltimore MACS (Todd Brown and Joseph Margolick), U01-HL146201; Johns Hopkins University, MACS Data Analysis and Coordination Center (Gypsyamber D?Souza, Stephen Gange and Elizabeth Golub), U01HL146193; Northwestern University, Chicago MACS (Steven Wolinsky), U01-HL146240; University of California, Los Angeles MACS (Roger Detels and Matthew Mimiaga), U01-HL146333; University of Pittsburgh MACS (Jeremy Martinson and Charles Rinaldo), U01-HL146208. The authors gratefully acknowledge the contributions of the study participants and dedication of the staff at the MWCCS sites. The authors thank Jay Hayes and Kathy Kulka from the Pittsburgh MACS for laboratory technical support, Jeffrey Toth from the Pittsburgh MACS data center and Andrea Stronski from the Center for the Analysis of MACS data for data support, Dr. Bernard J. Macatangay for providing laboratory facility support for the cyokine testing, Dr. John Mellors and Dr. Steven Wolinsky for the helpful comments, and especially the original, 1984?1985 participants of the Multicenter AIDS Cohort Study without whom this study would not be possible.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: Men 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]). Results: We 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. Conclusions: 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. This was associated with increased inflammatory biomarkers in the blood and risk for development of AIDS. [MediaObject not available: see fulltext.]
AB - Background: Men 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]). Results: We 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. Conclusions: 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. This was associated with increased inflammatory biomarkers in the blood and risk for development of AIDS. [MediaObject not available: see fulltext.]
KW - AIDS
KW - Fecal microbiome
KW - HIV seroconversion
KW - Inflammation
KW - MSM (men who have sex with men)
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U2 - 10.1186/s40168-021-01168-w
DO - 10.1186/s40168-021-01168-w
M3 - Article
C2 - 34879869
AN - SCOPUS:85120893872
SN - 2049-2618
VL - 9
JO - Microbiome
JF - Microbiome
IS - 1
M1 - 237
ER -