Gut Microbiota and Cognitive Function among Women Living with HIV

Background: Altered gut microbiota has been associated with cognitive dysfunction and Alzheimer's disease, but little is known among people living with HIV. Objective: To examine associations between gut microbiota and cognitive impairment among women with or without HIV. Methods: This is a cross-sectional study of 446 women (302 HIV+) who had completed a neuropsychological test battery and stool sample collected within 1 year. Gut microbiota composition was quantified using 16SV4 rRNA gene sequencing and microbial functional pathways were predicted using PICRUSt. Cognitive domains included attention, executive function, learning, memory, fluency, processing speed, and motor function. Cognitive impairment was defined as two or more domains with T scores<1 SD below mean. ANCOM-II was used to identify taxa and functional pathways associated with cognitive impairment, and the associations were further examined by multivariable logistic regression. Results: In overall sample, adjusting for multiple covariates including HIV status, we found that higher abundance of Methanobrevibacter, Odoribacter, Pyramidobacter, Eubacterium, Ruminococcus, and Gemmiger, and lower abundance of Veillonella were associated with cognitive impairment. The associations between these taxa and cognitive impairment were more profound in HIV+ women compared to HIV- women. Most associations with bacterial taxa were observed for learning and memory. We found accompanying microbial functional differences associated with cognitive impairment, including twelve enriched pathways and three depleted pathways. Conclusions: In women with or without HIV infection, this study identified multiple altered gut bacterial taxa and functional pathways associated with cognitive impairment, supporting the potential role of gut microbiota in cognitive dysfunction and Alzheimer's disease.