1. An Investigation into the Relationship of Circulating Gut Microbiome Molecules and Inflammatory Markers with the Risk of Incident Dementia in Later Life.
- Author
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Oluwagbemigun K, Anesi A, Vrhovsek U, Mattivi F, Martino Adami P, Pentzek M, Scherer M, Riedel-Heller SG, Weyerer S, Bickel H, Wiese B, Schmid M, Cryan JF, Ramirez A, Wagner M, and Nöthlings U
- Subjects
- Humans, Female, Male, Aged, 80 and over, Aged, Risk Factors, Cohort Studies, Incidence, Inflammation Mediators blood, Gastrointestinal Microbiome, Dementia blood, Dementia epidemiology, Dementia microbiology, Biomarkers blood, Inflammation blood
- Abstract
The gut microbiome may be involved in the occurrence of dementia primarily through the molecular mechanisms of producing bioactive molecules and promoting inflammation. Epidemiological evidence linking gut microbiome molecules and inflammatory markers to dementia risk has been mixed, and the intricate interplay between these groups of biomarkers suggests that their joint investigation in the context of dementia is warranted. We aimed to simultaneously investigate the association of circulating levels of selected gut microbiome molecules and inflammatory markers with dementia risk. This case-cohort epidemiological study included 805 individuals (83 years, 66% women) free of dementia at baseline. Plasma levels of 19 selected gut microbiome molecules comprising lipopolysaccharide, short-chain fatty acids, and indole-containing tryptophan metabolites as well as four inflammatory markers measured at baseline were linked to incident all-cause (ACD) and Alzheimer's disease dementia (AD) in binary outcomes and time-to-dementia analyses. Independent of several covariates, seven gut microbiome molecules, 5-hydroxyindole-3-acetic acid, indole-3-butyric acid, indole-3-acryloylglycine, indole-3-lactic acid, indole-3-acetic acid methyl ester, isobutyric acid, and 2-methylbutyric acid, but no inflammatory markers discriminated incident dementia cases from non-cases. Furthermore, 5-hydroxyindole-3-acetic acid (hazard ratio: 0.58; 0.36-0.94, P = 0.025) was associated with time-to-ACD. These molecules underpin gut microbiome-host interactions in the development of dementia and they may be crucial in its prevention and intervention strategies. Future larger epidemiological studies are needed to confirm our findings, specifically in exploring the repeatedly measured circulating levels of these molecules and investigating their causal relationship with dementia risk., Competing Interests: Declarations. Ethics Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Commission of the University of Bonn 050/02, 258/07; the Ethics Commission of the Medical Faculty of the Heinrich Heine University Düsseldorf 2079/2002, 2999/2008; the Ethics Commission of the Medical Association Hamburg OB/08/02, 2817/2007; and the Ethics Commission at the Medical Center of the University of Leipzig 143/2002, 309/2007. The ethical approval for the present biomarker analysis was obtained from the Ethics Commission of the University of Bonn 245/22. Consent to Participate: Informed consent was obtained from all individuals included in the study. Consent for Publication: Not applicable. Competing Interests: The authors have no competing interests to declare that are relevant to the content of this article., (© 2023. The Author(s).)
- Published
- 2024
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