Gut Microbiota and Cognitive Function Among Women Living with HIV

Article type: Research Article

Authors: Hua, Simin^{a; b} | Peters, Brandilyn A.^b | Lee, Susie^c | Fitzgerald, Kathryn^d | Wang, Zheng^b | Sollecito, Christopher C.^e | Grassi, Evan^e | Wiek, Fanua^e | St Peter, Lauren^e | D’Souza, Gypsyamber^f | Weber, Kathleen M.^g | Kaplan, Robert C.^{b; h} | Gustafson, Deborahⁱ | Sharma, Anjali^j | Burk, Robert D.^{b; e; k} | Rubin, Leah H.^{d; f} | Qi, Qibin^{b; l; *}

Affiliations: [a] Department of Population Health, Division of Epidemiology, New York University Grossman School of Medicine, New York, NY, USA | [b] Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA | [c] Department of Anesthesiology, Nuvance Health, Norwalk Hospital, Norwalk, CT, USA | [d] Johns Hopkins University School of Medicine, Baltimore, MD, USA | [e] Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA | [f] Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA | [g] Hektoen Institute of Medicine/Cook County Health, Chicago, IL, USA | [h] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA | [i] Department of Neurology, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA | [j] Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA | [k] Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA | [l] Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

Correspondence: [*] Correspondence to: Dr. Qibin Qi, Associate Professor, Albert Einstein College of Medicine, Department of Epidemiology and Population Health, 1300 Morris Park Ave, Belfer Building 1306, Bronx, NY, 10461, USA. Tel.: +1 718 430 4203; E-mail: [email protected].

Abstract: 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.

Keywords: Alzheimer’s disease, cognitive impairment, gut microbiome, HIV, human, women

DOI: 10.3233/JAD-230117

Journal: Journal of Alzheimer's Disease, vol. 95, no. 3, pp. 1147-1161, 2023