Possible Crosstalk & Alterations in Gut Bacteriome and Virome in HIV-1 Infection and the Associated Co-Morbidities Related to Metabolic Disorder

Increased life expectancy and better medication is allowing People living with HIV (PLWH) to live more. At the same time, other complications like Metabolic syndrome (MetS) are coming up as new challenges to handle. This review aims to explore the emerging evidence of gut microbiome and virome alterations in Human Immunodeficiency Virus-1 (HIV-1) infection and associated metabolic disorders- such as type-2 diabetes and cardiovascular disease, with a focus on their interplay, contribution to immune dysfunction, and potential as therapeutic targets. We conducted a comprehensive review of current literature on gut bacteriome and virome changes in HIV-1-infected individuals and those with metabolic comorbidities. Studies examining microbial translocation, immune activation, and potential interventions like phage therapy and faecal virome transplantation were evaluated. HIV-1 infection disrupts gut microbial homeostasis, promoting bacterial translocation, systemic inflammation, and metabolic dysregulation. Similarly, metabolic disorders are marked by reduced beneficial short-chain fatty acid-producing bacteria and an increase in pro-inflammatory taxa. Alterations in the gut virome, particularly involving bacteriophages, may exacerbate bacterial dysbiosis and immune dysfunction. Conversely, some viral populations have been associated with immune restoration post-ART. These findings point toward a dynamic and bidirectional relationship between the gut virome, bacteriome, and host immunity. Understanding the complex crosstalk between the gut virome and microbiome in HIV-1 and metabolic disease is crucial for identifying microbial signatures that may serve as biomarkers or therapeutic targets. Targeted interventions such as microbiome modulation, phage therapy, and faecal virome transplantation (FVT) offer promising avenues for restoring gut homeostasis and improving long-term outcomes in PLWH.