Diet-Microbiota-Brain Axis in Alzheimer's Disease

Abstract

Background: Alzheimer's disease (AD) is the most common form of dementia, particularly in older adults, with clinical manifestations of progressive cognitive decline and functional impairment. The prevalence of AD and related dementia is mounting worldwide, but its etiology remains unresolved, with no available preventative or ameliorative therapy. Emerging evidence suggests that the gut microbiota of patients with AD is different from cognitively normal counterparts.

Summary: Communication between gut and brain (gut-brain axis) plays a crucial role in AD pathology. Bacteria inhabiting the gut strongly influence this gut-brain axis and thus may participate in AD pathology. Diet, one of the strongest modulators of gut microbiota, also strongly influences brain health and AD pathology. Gut microbiota metabolites including short-chain fatty acids, pro-inflammatory factors, and neurotransmitters may also affect AD pathogenesis and associated cognitive decline. Therefore, investigation of diet-microbiota-brain axis is important to better understand its contribution in AD pathology and its potential use as a target to prevent and treat AD. Herein, we discuss the link between AD and gut microbiota and ponder how microbiota modulation through nutritional approaches may offer avenues for discovering novel preventive and therapeutic strategies against AD. Key Message: A strong association exists between lifestyle factors and AD prevalence wherein unhealthy dietary factors have been linked to neurodegeneration. Specific prudent dietary patterns might help in preventing or delaying AD progression by affecting β-amyloid production and tau processing and regulating AD-associated inflammation, metabolism and oxidative stress, plausibly via modulating gut microbiota.

Keywords: Amyloid; Cognition; Dementia; Microbiota; Neurodegenerative disease; Tau.

Fig. 1.

Schematic representation of the putative links connecting diet-microbiome interaction with brain and cognitive health in subjects with MCI and AD. Aβ, amyloid-beta; BBB, blood-brain barrier; BDNF, brain-derived neurotrophic factor; DASH, dietary approaches to stop hypertension diet; HFD, high-fat diet; HSD, high-sugar diet; MD, Mediterranean diet; MIND, Mediterranean-DASH Intervention for Neurodegenerative Delay diet; NMDAR, N-methyl-d-aspartate receptor; SCFA, short-chain fatty acids; WD, Western-style diet; AD, Alzheimer’s disease; MCI, mild cognitive impairment.