Resilient gut microbiome is linked to immune control in HIV-1 infection

HIV-1 affects millions of people globally, and in rare cases, individuals known as “elite controllers” (EC) maintain undetectable viral load without antiretroviral therapy (ART). Given the crucial role of the gut microbiota in maintaining immune system homeostasis, this study investigated its composition and functionality in people living with HIV (PLHIV) (including viremic individuals, ART-treated individuals, and ECs) and healthy donors (HD). Fecal samples were collected for quantification of short-chain fatty acids (SCFAs), 16S rRNA sequencing, and bioinformatic analysis of taxonomic and functional profiles. ECs and HDs exhibited a similar microbiota, characterized by higher abundance of Bacteroidetes and species associated with anti-inflammatory profiles, such as Bacteroides vulgatus and Bacteroides uniformis, and greater ecological diversity. Viremic individuals (VR) showed predominance of Ruminococcus and Eubacterium hallii, both associated with inflammation and unfavorable clinical progression. SCFAs such as acetate, butyrate, and propionate increased HIV replication in vitro, suggesting a possible role in viral reactivation. Functional analysis revealed differences in bacterial metabolic profiles in PLHIV, primarily in carbohydrate and amino acid metabolism. This study highlights the potential of the gut microbiota in modulating HIV-1 progression. Therapeutic strategies aimed at restoring an EC-like microbiota composition may contribute to viral control and reduction of inflammation in PLHIV.