Abstract
The intesinal microbiome is considered important in human immunodeficiency virus (HIV) pathogenesis and therefore represents a potential therapeutic target to improve the patients’ health status. Longitudinal alterations in the colonic mucosa-associated microbiome during simian immunodeficiency virus (SIV) infection were investigated using a 16S rRNA amplicon approach on the Illumina sequencing platform and bioinformatics analyses. Following SIV infection of six animals, no alterations in microbial composition were observed before the viral load peaked in the colon. At the time of acute mucosal SIV replication, the phylum Bacteroidetes including the Bacteroidia class as well as the phylum Firmicutes and its families Ruminococcaceae and Eubacteriaceae became more abundant. Enrichment of Bacteroidetes was maintained until the chronic phase of SIV infection. The shift towards Bacteroidetes in the mucosa-associated microbiome was associated with the extent of SIV infection-induced mucosal CD4+ T cell depletion and correlated with increasing rates of enterocyte damage. These observations suggest that Bacteroidetes strains increase during virus-induced mucosal immune destruction. As Bacteroidetes belong to the lipopolysaccharide- and short chain fatty acids-producing bacteria, their rapid enrichment may contribute to inflammatory tissue damage and metabolic alterations in SIV/HIV infection. These aspects should be considered in future studies on therapeutic interventions.
Highlights
The intesinal microbiome is considered important in human immunodeficiency virus (HIV) pathogenesis and represents a potential therapeutic target to improve the patients’ health status
During the chronic phase on day 49 post-infection (‘chronic simian immunodeficiency virus (SIV)’), CD4+ T cells remained at low levels in five animals or were restored to some extent in one animal which presented with lowest mucosal SIV DNA levels during both infection phases analyzed (Fig. 1A, B)
One major finding is the shift towards Gram-negative Bacteroidetes in the colonic mucosa-adherent microbiome, including members of the Bacteroidia class, that was first observed at the time of mucosal virus peak, was maintained up to the chronic phase, and was associated with the extent of colonic CD4+ T cell depletion
Summary
The intesinal microbiome is considered important in human immunodeficiency virus (HIV) pathogenesis and represents a potential therapeutic target to improve the patients’ health status. The shift towards Bacteroidetes in the mucosa-associated microbiome was associated with the extent of SIV infection-induced mucosal C D4+ T cell depletion and correlated with increasing rates of enterocyte damage. These observations suggest that Bacteroidetes strains increase during virus-induced mucosal immune destruction. As Bacteroidetes belong to the lipopolysaccharide- and short chain fatty acids-producing bacteria, their rapid enrichment may contribute to inflammatory tissue damage and metabolic alterations in SIV/HIV infection. These aspects should be considered in future studies on therapeutic interventions. We studied the composition of the colonic mucosa-associated microbiome within individual rhesus macaques before and during the course of SIVmac infection
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