Feeding the gut-immune axis: dietary, prebiotic, and probiotic strategies to target persistent inflammation in ART-treated HIV: a narrative review.

People living with HIV (PWH) experience ongoing systemic inflammation driven by gut dysbiosis, epithelial barrier disruption, and microbial translocation, despite antiretroviral therapy (ART). This review examines evidence from randomized controlled trials, mechanistic studies, systematic reviews, and meta-analyses evaluating nutritional and microbiome-based interventions to reduce inflammation in PWH. Reduced production of short-chain fatty acids (SCFAs) by the gut microbiota has been observed to precede morbidity and mortality in PWH, with SCFAs, mainly butyrate, exerting immunomodulatory effects through promoting regulatory T-cell differentiation via histone deacetylase inhibition and G protein-coupled receptor 43 (GPR43) and GPR109A signaling, suppressing nuclear factor kappa B (NF-κB)-mediated pro-inflammatory cytokine production, and enhancing epithelial tight junction integrity. Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation have demonstrated reductions in inflammatory biomarkers including soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP), and high-sensitivity C-reactive protein (hsCRP). The Mediterranean diet, omega-3 fatty acids, and polyphenol-rich foods represent an underexplored area as modulators of gut microbiota composition and SCFA production. Existing gaps in the literature include a lack of trials with clinically meaningful endpoints, optimal probiotic strains and doses, and lack of randomized trials evaluating anti-inflammatory dietary patterns in PWH. We propose a research agenda prioritizing Mediterranean diet intervention trials, precision microbiome interventions, and combination approaches integrating dietary modification with microbiome-targeted therapies. Lastly, we provide practical nutritional recommendations for clinicians managing PWH.