Gut-Brain Axis Physiology and Its Role in the Pathogenesis of Depression in HIV-Infected Adults in Lagos: A Mechanistic Cohort Study

The gut-brain axis, comprising bidirectional communication between gut microbiota and the central nervous system, is hypothesised to contribute to depression pathogenesis in HIV infection, yet this relationship has never been mechanistically examined in African populations. This study investigated gut-brain axis physiology and its mechanistic role in depression among HIV-infected adults in Lagos, South West Nigeria, making an original scientific contribution at the intersection of infectious disease physiology and neuropsychiatry. A longitudinal observational cohort enrolled 100 HIV-positive adults on antiretroviral therapy and 50 HIV-negative controls. Depression was assessed at baseline and twelve months using the Beck Depression Inventory. Gut microbiome composition was characterised by 16S rRNA sequencing from stool samples. Serum short-chain fatty acids, lipopolysaccharide-binding protein as an intestinal permeability marker, brain-derived neurotrophic factor, and inflammatory cytokines were measured at each time point. Mediation analysis using causal modelling examined the gut-brain pathway. Results showed that HIV-positive adults had significantly reduced microbiome diversity and short-chain fatty acid concentrations, elevated lipopolysaccharide-binding protein, and lower brain-derived neurotrophic factor. Depression incidence at twelve months was significantly higher in HIV-positive participants and correlated inversely with microbial diversity. Mediation analysis confirmed that intestinal permeability and reduced brain-derived neurotrophic factor sequentially mediated the microbiome-depression relationship. This study establishes the first mechanistic gut-brain axis evidence for HIV-related depression in Nigeria. Probiotic and dietary microbiome interventions targeting depression prevention in HIV programmes are proposed. Keywords: gut-brain axis, HIV, depression, microbiome, Lagos.