Fig. 1

Hypothetical dynamics of bacteria modulation on HIV reservoir. Increased abundance and dissemination of bacterial-derived (i.e. Prevotella and Bacteroides species) inflammatory mediators, such as LPS, may induce host immune activation and acute inflammation, triggering prompt response to targeted HIV interventions, thus ultimately influencing the establishment of HIV-1 reservoirs. In contrast, anti-inflammatory bacteria, including butyrate producers, may promote an immune quiescent state and limit host immune response to specific treatments. Microbial metabolites, including SCFAs and BAs, may act as regulators of Treg differentiation, TGF-β secretion, and histone deacetylation inhibitors, modulating the latent HIV reservoir. Directionality and, by extension, causality in the proposed hypothetical framework underlying the interplay between HIV reservoir and microbiota remain uncertain. Abbreviations: BAs, bile acids; HDAC, histone deacetylase; HIV, human immunodeficiency virus; IFN, interferon; LPS, lipopolysaccharide; PSA, polysaccharide A; LOS, lipooligosaccharide; SCFAs, short-chain fatty acids; TGF-β, transforming growth factor beta. Figure generated with BioRender.com