Manipulation of the diet–microbiota–brain axis in Alzheimer’s disease

Abstract

Several studies investigating the pathogenesis of Alzheimer’s disease have identified various interdependent constituents contributing to the exacerbation of the disease, including Aβ plaque formation, tau protein hyperphosphorylation, neurofibrillary tangle accumulation, glial inflammation, and the eventual loss of proper neural plasticity. Recently, using various models and human patients, another key factor has been established as an influential determinant in brain homeostasis: the gut–brain axis. The implications of a rapidly aging population and the absence of a definitive cure for Alzheimer’s disease have prompted a search for non-pharmaceutical tools, of which gut-modulatory therapies targeting the gut–brain axis have shown promise. Yet multiple recent studies examining changes in human gut flora in response to various probiotics and environmental factors are limited and difficult to generalize; whether the state of the gut microbiota in Alzheimer’s disease is a cause of the disease, a result of the disease, or both through numerous feedback loops in the gut–brain axis, remains unclear. However, preliminary findings of longitudinal studies conducted over the past decades have highlighted dietary interventions, especially Mediterranean diets, as preventative measures for Alzheimer’s disease by reversing neuroinflammation, modifying the intestinal and blood–brain barrier (BBB), and addressing gut dysbiosis. Conversely, the consumption of Western diets intensifies the progression of Alzheimer’s disease through genetic alterations, impaired barrier function, and chronic inflammation. This review aims to support the growing body of experimental and clinical data highlighting specific probiotic strains and particular dietary components in preventing Alzheimer’s disease via the gut–brain axis.

Can the gut microbiome inform the effects of omega-3 fatty acid supplementation trials on cognition?

“…Several studies in animal models of AD also support this observation and offer changes to the gut microbiota as a culprit. The human gastrointestinal tract houses the largest reservoir of microbes in humans, containing more than 1000 distinct microbial species [7 ▪ ,8]. The central nervous system (CNS) and the gut microbiota bidirectionally influence each other, described as the gut–brain axis.…”

“…The gut–brain axis functions via mechanisms, such as microbial products and byproducts, the vagus nerve, the enteric nervous system, and the hormones. The products and byproducts of bacterial metabolism released to the gut include lipopolysaccharides (LPSs) and amyloids, which are pro-inflammatory, as well as short chain fatty acids (SCFAs) such as butyrate, which are anti-inflammatory [6,7 ▪ ,9]. Moreover, the number of pro-inflammatory intestinal bacteria positively correlates with pro-inflammatory cytokines in the blood [6].…”

“…Indeed, therapeutic remodeling of the gut microbiota appears to ameliorate AD pathogenesis in animal models [16–18]. Dietary interventions in humans involving probiotic supplements, increased fermented food intake, and shift to healthier diets such as the Mediterranean diet have beneficial effects on the gut microbiota but their effectiveness in improving cognition has shown mixed results [7 ▪ ].…”

Lipids, Gut Microbiota, and the Complex Relationship with Alzheimer’s Disease: A Narrative Review

“…SCFAs are produced by the fermentation of non-digestible carbohydrates, mainly by gram-positive bacteria, with acetate, propionate, and butyrate, which serve as protective factors for the GBMA. They provide energy to intestinal cells, promote intestinal barrier integrity, and prevent the proliferation of pathogenic bacteria associated with AD development by altering the intestinal pH, as well as stimulating anti-inflammatory mediators [25]. Furthermore, they can traverse the intestinal tract and the circulatory system, cross the BBB, and reach the brain, where they act as agonists of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor in microglia and astrocyte cells, reducing inflammation, neurotoxicity, and immune cell chemotaxis [22].…”

Photobiomodulation in Alzheimer’s Disease—A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

“…), smoking, alcohol abuse, sedentary lifestyle, sleep disorders, infections, and toxic environmental factors (heavy metals, trace metals, and others). Clinically, there are two types of AD: the early-onset type, which occurs in younger people, accounting for a small percentage of up to 5% of cases, and the late-onset type, known as loading or sporadic, which is the most common [ 20 , 21 , 22 , 23 ].…”