Unique Oral Microbiota Signatures and Neurocognitive Function in Adolescents with and without Perinatally Acquired HIV

Abstract Adolescents with perinatally acquired HIV (PHIV) on antiretroviral therapy (ART) face early neurocognitive and oral disease, yet links between the oral microbiome and cognition remain underexplored. We analyzed baseline data from 53 PHIV and 47 age-, sex-, and socioeconomically matched HIV-unexposed-uninfected (HUU) adolescents (10–13 years) in Nigeria. Cognition was assessed with NeuroScreen and the NIH Toolbox. Oral rinse shotgun metagenomes were profiled for microbial diversity, community structure, and species-level differential abundance using five complementary methods stratified by HIV serostatus. Taxa were considered robust when concordant across at least two methods. Diversity and community structure did not significantly differ by HIV (Bray-Curtis PERMANOVA R 2  = 0.017, p = 0.11) or across cognitive gradients, however at the species level, reproducible taxon-level signals emerged. In PHIV, Leptotrichia , Tannerella , Actinomyces , and Prevotella were associated with higher performance. In HUU, Neisseria sp. was associated with lower-cognitive performance across analyses in the HUU groups. Streptococcus associations differed in direction by HIV stratum. In this cross-sectional analyses, distinct oral taxa are associated with neurocognitive health in an HIV-context-dependent manner, identifying candidate markers of the oral-brain axis. Longitudinal, multi-omic studies are needed to test directionality and mechanism of action as candidate intervention targets.