Interaction Between Diet and Microbiota in the Pathophysiology of Alzheimer’s Disease: Focus on Polyphenols and Dietary Fibers

Article type: Review Article

Authors: Ticinesi, Andrea^{a; b; c; *} | Mancabelli, Leonardo^d | Carnevali, Luca^d | Nouvenne, Antonio^{a; b; c} | Meschi, Tiziana^{a; b; c} | Del Rio, Daniele^{a; e} | Ventura, Marco^{a; d} | Sgoifo, Andrea^{a; d} | Angelino, Donato^f

Affiliations: [a] Microbiome Research Hub, University of Parma, Parma, Italy | [b] Department of Medicine and Surgery, University of Parma, Parma, Italy | [c] Geriatric-Rehabilitation Department, Parma University-Hospital, Parma, Italy | [d] Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy | [e] Department of Food and Drugs, University of Parma, Parma, Italy | [f] Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy

Correspondence: [*] Correspondence to: Dr. Andrea Ticinesi, MD, PhD, Microbiome Research Hub and Department of Medicine and Surgery, University of Parma, Geriatric-Rehabilitation Department, Azienda Ospedaliero-Universitaria di Parma, Via Antonio Gramsci 14, 43126 Parma, Italy. Tel.: +39 0521 703871; Fax: +39 0521702383; E-mails: [email protected]; [email protected]; ORCID-ID: 0000-0001-9171-8592

Abstract: Animal studies increasingly indicate that the gut microbiota composition and function can be involved in the pathophysiology and progression of Alzheimer’s disease (AD) at multiple levels. However, few studies have investigated this putative gut-brain axis in human beings, and none of them considered diet as a determinant of intestinal microbiota composition. Epidemiological studies highlight that a high intake of fruit and vegetables, such as that typical of the Mediterranean diet, can modulate AD progression. Thus, nutritional interventions are being increasingly studied as a possible non-pharmacological strategy to slow down the progression of AD. In particular, polyphenols and fibers represent the nutritional compounds with the higher potential of counterbalancing the pathophysiological mechanisms of dementia due to their antioxidant, anti-inflammatory, and anti-apoptotic properties. These actions are mediated by the gut microbiota, that can transform polyphenols and fibers into biologically active compounds including, among others, phenyl-γ-valerolactones, urolithins, butyrate, and other short-chain fatty acids. In this review, the complex mechanisms linking nutrition, gut microbiota composition, and pathophysiology of cognitive decline in AD are discussed, with a particular focus on the role of polyphenols and fibers. The gaps between pre-clinical and clinical studies are particularly emphasized, as well as the urgent need for studies comprehensively evaluating the link between nutrition, microbiome, and clinical aspects of AD.

Keywords: Aging, butyrate, cognitive impairment, short-chain fatty acids

DOI: 10.3233/JAD-215493

Journal: Journal of Alzheimer's Disease, vol. 86, no. 3, pp. 961-982, 2022