Evolution of the gut microbiome following acute HIV-1 infection

Abstract

Background In rhesus macaques, simian immunodeficiency virus infection is followed by expansion of enteric viruses but has a limited impact on the gut bacteriome. To understand the longitudinal effects of HIV-1 infection on the human gut microbiota, we prospectively followed 49 Mozambican subjects diagnosed with recent HIV-1 infection (RHI) and 54 HIV-1-negative controls for 9–18 months and compared them with 98 chronically HIV-1-infected subjects treated with antiretrovirals ( n = 27) or not ( n = 71). Results We show that RHI is followed by increased fecal adenovirus shedding, which persists during chronic HIV-1 infection and does not resolve with ART. Recent HIV-1 infection is also followed by transient non-HIV-specific changes in the gut bacterial richness and composition. Despite early resilience to change, an HIV-1-specific signature in the gut bacteriome—featuring depletion of Akkermansia , Anaerovibrio , Bifidobacterium , and Clostridium— previously associated with chronic inflammation, CD8+ T cell anergy, and metabolic disorders, can be eventually identified in chronically HIV-1-infected subjects. Conclusions Recent HIV-1 infection is associated with increased fecal shedding of eukaryotic viruses, transient loss of bacterial taxonomic richness, and long-term reductions in microbial gene richness. An HIV-1-associated microbiome signature only becomes evident in chronically HIV-1-infected subjects. Electronic supplementary material The online version of this article (10.1186/s40168-019-0687-5) contains supplementary material, which is available to authorized users.

The Bacterium Akkermansia muciniphila: A Sentinel for Gut Permeability and Its Relevance to HIV-Related Inflammation

“…Rocafort et al confirmed and expanded these results by showing that A. muciniphila abundance was significantly higher in 49 recently infected PLWH and 55 healthy controls compared to 71 chronically infected untreated PLWH. Furthermore, in 27 chronically infected ART-treated PLWH, A. muciniphila abundance was similar to healthy controls (101). These findings suggest that chronic HIV infection leads to progressive depletion of A. muciniphila abundance, and following ART initiation, A. muciniphila abundance returns to levels similar to those of healthy controls.…”

“…Bacterial communities residing in the intestine of HIVinfected individuals have been shown to differ from those of individuals not infected with HIV, independently of age, sex and sexual practice (6). Dysbiosis is associated with impaired intestinal barrier activity, impaired mucosal immunity function and worse clinical outcome in PLWH (6,16,100,101). Moreover, A. muciniphila was significantly depleted in ART-naïve and ART-treated PLWH, compared to uninfected controls (101,102).…”

“…Dysbiosis is associated with impaired intestinal barrier activity, impaired mucosal immunity function and worse clinical outcome in PLWH (6,16,100,101). Moreover, A. muciniphila was significantly depleted in ART-naïve and ART-treated PLWH, compared to uninfected controls (101,102). In one study, Mutlu et al demonstrated that PLWH had significantly less A. muciniphila abundance regardless of ART, CD4 count or viral load, compared to healthy controls (102).…”

“…HIV infection, metabolic disorders and cancer share common features such as chronic inflammation and dysbiosis, which includes the decreased abundance of A. muciniphila in the gut microbiota (4,40,71,(101)(102)(103)(104). Given this decreased abundance of A. muciniphila in PLWH, and considering the benefits of increasing A. muciniphila abundance in obesity, we hypothesize that A. muciniphila can act as a shield for gut permeability, preventing microbial translocation and reducing inflammation, with the aim toward decreasing risks of developing non-AIDS comorbidities in PLWH.…”

Microbiome Stability with Chronic SIV Infection in AIDS-resistant Sooty Mangabeys

“…The profound disruption of mucosal immunity by HIV/SIV infection has instigated several studies on its impact on the mucosal microbiome in humans and NHPs(reviewed in (15, 16)). In PLWH, a general reduction of gastrointestinal microbiota richness, bacterial community dysbiosis, and opportunistic pathogenic taxa enrichment relative to healthy controls has been consistently reported(17-19). HIV patients on ART have been observed to retain a persistent perturbance of microbiota and enrichment of potentially pathogenic bacteria(17, 18), which has been linked to immunological factors potentiating mucosal inflammation(18).…”