Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

Abstract

Background The potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial. Results Viremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size. Conclusions The present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption.

Analysis of Bacteriophage Behavior of a Human RNA Virus, SARS-CoV-2, through the Integrated Approach of Immunofluorescence Microscopy, Proteomics and D-Amino Acid Quantification

“…These connections begin to be evident during viruses’ general defense, invasion, and replication phases [ 60 , 61 ]. In fact, reviewing the existing literature on HIV [ 62 , 63 , 64 , 65 , 66 , 67 ] and poliovirus [ 68 ], other RNA viruses also appear to have significant involvement in the gut microbiome. In fact, a recent study observed HIV gene sequences in bacteria isolated from the oropharyngeal tract of Kenyan children [ 63 ], and this finding is synergic with the diatribe of the bacterial cofactor in HIV and its connection with mycoplasmas [ 66 ].…”

HIV Tat Expression and Cocaine Exposure Lead to Sex- and Age-Specific Changes of the Microbiota Composition in the Gut

“…HIV infection is also associated with decreased abundance, composition, and diversity of gut microbiota. These changes in turn contribute to persistent inflammation and microbial translocation, dysfunctional metabolism of the host, and HIV disease progression and reservoir size [ 26 , 27 , 28 , 29 , 30 ]. Importantly, antiretroviral therapy does not fully restore the integrity of the gut epithelial barrier and the disrupted gut microbiota that result from HIV infection despite its potent suppressive effects on HIV replication [ 27 , 31 ].…”

The immunological interplay between vaccination and the intestinal microbiota

“…These studies have reported inconsistent results. In humans, the administration of oral typhoid or an intranodal and intramuscularly human immunodeficiency virus (HIV)-1 vaccine was not reported to significantly affect the composition of the intestinal microbiota one week to several months after vaccination 12 , 21 , 22 . The first two studies used amplicon sequencing, while the third used shotgun metagenomic sequencing.…”

“…Only a few studies have investigated whether the administration of vaccines is associated with changes in the composition of the intestinal microbiota 12,[20][21][22][23][24][25][26] , and whether the changes induced by vaccination, in turn, influence vaccine immunogenicity 20 . These studies have reported inconsistent results.…”