From dysbiosis to defense: harnessing the gut microbiome in HIV/SIV therapy

Abstract

Background: Although the microbiota has been extensively associated with HIV pathogenesis, the majority of studies, particularly those using omics techniques, are largely correlative and serve primarily as a basis for hypothesis generation. Furthermore, most have focused on characterizing the taxonomic composition of the bacterial component, often overlooking other levels of the microbiome. The intricate mechanisms by which the microbiota influences immune responses to HIV are still poorly understood. Interventional studies on gut microbiota provide a powerful tool to test the hypothesis of whether we can harness the microbiota to improve health outcomes in people with HIV.

Results: Here, we review the multifaceted role of the gut microbiome in HIV/SIV disease progression and its potential as a therapeutic target. We explore the complex interplay between gut microbial dysbiosis and systemic inflammation, highlighting the potential for microbiome-based therapeutics to open new avenues in HIV management. These include exploring the efficacy of probiotics, prebiotics, fecal microbiota transplantation, and targeted dietary modifications. We also address the challenges inherent in this research area, such as the difficulty in inducing long-lasting microbiome alterations and the complexities of study designs, including variations in probiotic strains, donor selection for FMT, antibiotic conditioning regimens, and the hurdles in translating findings into clinical practice. Finally, we speculate on future directions for this rapidly evolving field, emphasizing the need for a more granular understanding of microbiome-immune interactions, the development of personalized microbiome-based therapies, and the application of novel technologies to identify potential therapeutic agents.

Conclusions: Our review underscores the importance of the gut microbiome in HIV/SIV disease and its potential as a target for innovative therapeutic strategies.

Fig. 1

Therapeutic interventions targeting the microbiome in PWH. Left panel: GALT immune function and HIV disruption: healthy conditions, complex microbiome and balanced immune response in the GALT; HIV effects, altered microbiome, damaged enterocyte barrier, increased bacterial translocation, CD4 T-cell loss, CD8 T-cell expansion, neutrophil infiltration, local and systemic inflammation. Right panel: Intervention strategies and future directions: diet and prebiotics, Mediterranean diet and prebiotics promote growth of beneficial bacteria; probiotics, targeted addition of beneficial bacteria; FMT, replacing patient’s microbiota with a donor’s healthy microbiome; current state of evidence, interventions potentially reduce inflammation but lack sufficient clinical backing for recommendation; research prospects, future studies aim to produce targeted microbial consortia or postbiotics with heightened precision and efficacy