Gut microbiota composition in HIV-exposed uninfected children in the low and middle-income settings: a comparative study based on 16S rRNA sequencing with HIV-unexposed controls

The successful prevention of vertical paediatric HIV transmission has led to an expanding cohort of 16 million HIV-exposed uninfected (HEU) children under 15 years of age, with 90% of them living in sub-Saharan Africa. These children face some health challenges from birth due to their exposure to HIV and antiretroviral therapy, associated with adverse maternal outcomes. Early life exposure to HIV/ART therapy may influence gut microbiome development in HEU children, particularly in resource-limited settings. This study examines the effects of perinatal exposure to HIV and ART on the microbiota of HIV-exposed uninfected children in Cameroon during early childhood, using the gold standard 16S rRNA sequencing method to analyse alpha and beta diversity metrics, differential abundance, and taxonomic profiles. The two study groups, exposed and unexposed uninfected children, were balanced in terms of clinical and demographic characteristics and showed no significant differences in alpha diversity. However, HEU children show gut microbiome dysbiosis compared to HIV-unexposed children, as indicated by changes in community structure with significant β-diversity differences (Wilcoxon test, p=0.022). Although exposure to maternal HIV infection, ART, and cotrimoxazole prophylaxis leaves a questionable mark on the microbiome, our study shows that Cameroonian HEU children possess a resilient gut microbiota that supports microbiome development despite these exposures. Their microbial gut communities maintain preserved alpha diversity and a taxonomic profile dominated by Segatella, an enterotype typical of populations with fibre-rich diets and agricultural lifestyles.