Affiliations: [a] School of Biomedical, Nutritional and Sport Sciences, Newcastle University, Newcastle upon Tyne, UK
| [b] Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| [c] Institute For Global Food Security, Queen’s University Belfast, Belfast, UK
| [d] Centre for Public Health, Queen’s University Belfast, Belfast, UK
| [e] Global Brain Health Institute, University of California San Francisco, San Francisco, CA, USA
| [f] Trinity College Dublin, Dublin, Ireland
Correspondence:
[*]
Correspondence to: Dr. Andrea Fairley, School of Biomedical, Nutritional and Sport Sciences, Newcastle University, Newcastle upon Tyne, UK. Tel.: +44 (0) 191 2080298; E-mail: andrea.mcgrattan@ncl.ac.uk.
Abstract: Given the complex bidirectional communication system that exists between the gut microbiome and the brain, there is growing interest in the gut microbiome as a novel and potentially modifiable risk factor for Alzheimer’s disease (AD). Gut dysbiosis has been implicated in the pathogenesis and progression of AD by initiating and prolonging neuroinflammatory processes. The metabolites of gut microbiota appear to be critical in the mechanism of the gut-brain axis. Gut microbiota metabolites, such as trimethylamine-n-oxide, lipopolysaccharide, and short chain fatty acids, are suggested to mediate systemic inflammation and intracerebral amyloidosis via endothelial dysfunction. Emerging data suggest that the fungal microbiota (mycobiome) may also influence AD pathology. Importantly, 60% of variation in the gut microbiome is attributable to diet, therefore modulating the gut microbiome through dietary means could be an effective approach to reduce AD risk. Given that people do not eat isolated nutrients and instead consume a diverse range of foods and combinations of nutrients that are likely to be interactive, studying the effects of whole diets provides the opportunity to account for the interactions between different nutrients. Thus, dietary patterns may be more predictive of a real-life effect on gut microbiome and AD risk than foods or nutrients in isolation. Accumulating evidence from experimental and animal studies also show potential effects of gut microbiome on AD pathogenesis. However, data from human dietary interventions are lacking. Well-designed intervention studies are needed in diverse populations to determine the influence of diet on gut microbiome and inform the development of effective dietary strategies for prevention of AD.
Keywords: Gut microbiome, gut metabolites, dietary patterns, Alzheimer’s disease
