The Oral and Fecal Microbiota in a Canadian Cohort of Alzheimer’s Disease

Article type: Research Article

Authors: Cirstea, Mihai S.^{a; b; c} | Kliger, Daniel^{c; d} | MacLellan, Abbey D.^c | Yu, Adam C.^c | Langlois, Jenna^{c; d} | Fan, Mannie^d | Boroomand, Seti^e | Kharazyan, Faezeh^e | Hsiung, Robin G.Y.^{d; f} | MacVicar, Brian A.^g | Chertkow, Howard^{h; i} | Whitehead, Victor^j | Brett Finlay, B.^{a; b; k; *; 1} | Appel-Cresswell, Silke^{c; f; 1}

Affiliations: [a] Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC, Canada | [b] Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada | [c] Pacific Parkinson’s Research Centre, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada | [d] Clinic for Alzheimer Disease and Related Disorders, University of British Columbia, Vancouver, BC, Canada | [e] Borgland Family Brain Tissue and DNA Bank, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada | [f] Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada | [g] Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada | [h] Baycrest and Rotman Research Institute, Toronto, ON, Canada | [i] Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada | [j] Lady Davis Institute for Medical Research, McGill University, Montreal, QC, Canada | [k] Department of Biochemistry, University of British Columbia, Vancouver, BC, Canada

Correspondence: [*] Correspondence to: Dr. B. Brett Finlay, PhD, OC, OBC, FRSC, FCAHS, Michael Smith Laboratories, University of British Columbia, 2185 E Mall, Vancouver, BC V6T 1Z4, Canada. Tel.: +1 604 822 2210; E-mail: [email protected].

Note: [1] These authors are co-senior authors.

Abstract: Background:Despite decades of research, our understanding of Alzheimer’s disease (AD) etiology remains incomplete. In recent years, appreciation has grown for potential roles for the microbiota in shaping neurological health. Objective:This study aimed to examine associations between the microbiota and AD in a human cross-sectional cohort. Methods:Forty-five AD patients and 54 matched controls were recruited in Vancouver, Canada. Fecal and oral samples underwent 16S microbiota sequencing. A wide array of demographic and clinical data were collected. Differences between participant groups were assessed, and associations between microbes and clinical variables were examined within the AD population. Results:The gut microbiota of AD patients displayed lower diversity relative to controls, although taxonomic differences were sparse. In contrast, the AD oral microbiota displayed higher diversity, with several taxonomic differences relative to controls, including a lower abundance of the families Streptococcaceae and Actinomycetaceae, and a higher abundance of Weeksellaceae, among others. The periodontitis-associated oral microbe Porphyromonas gingivalis was 5 times more prevalent among patients. No significant associations between gut or oral microbes and cognition were detected, but several correlations existed between microbes and mood disorders and BMI among patients, including a strong positive correlation between Alphaproteobacteria and depression score. Conclusion:The gut microbiota of AD patients was not overtly different from controls, although it displayed lower diversity, an overall marker of microbiota health. The oral microbiota did display marked differences. Cognition was not associated with a microbial signature, but other relevant AD factors including mood and BMI did demonstrate an association.

Keywords: Alzheimer’s disease, depression, microbiome, oral microbiome

DOI: 10.3233/JAD-215520

Journal: Journal of Alzheimer's Disease, vol. 87, no. 1, pp. 247-258, 2022