The Gut-Brain Axis in Alzheimer’s Disease and Omega-3. A Critical Overview of Clinical Trials

Abstract

Despite intensive study, neurodegenerative diseases remain insufficiently understood, precluding rational design of therapeutic interventions that can reverse or even arrest the progressive loss of neurological function. In the last decade, several theories investigating the causes of neurodegenerative diseases have been formulated and a condition or risk factor that can contribute is described by the gut-brain axis hypothesis: stress, unbalanced diet, and drugs impact altering microbiota composition which contributes to dysbiosis. An altered gut microbiota may lead to a dysbiotic condition and to a subsequent increase in intestinal permeability, causing the so-called leaky-gut syndrome. Herein, in this review we report recent findings in clinical trials on the risk factor of the gut-brain axis in Alzheimer’s disease and on the effect of omega-3 supplementation, in shifting gut microbiota balance towards an eubiosis status. Despite this promising effect, evidences reported in selected randomized clinical trials on the effect of omega-3 fatty acid on cognitive decline in Alzheimer’s disease are few. Only Mild Cognitive Impairment, a prodromal state that could precede the progress to Alzheimer’s disease could be affected by omega-3 FA supplementation. We report some of the critical issues which emerged from these studies. Randomized controlled trials in well-selected AD patients considering the critical points underlined in this review are warranted.

Metabolic Endotoxemia: A Potential Underlying Mechanism of the Relationship between Dietary Fat Intake and Risk for Cognitive Impairments in Humans?

“…Pre-and probiotics have demonstrated the ability to manipulate gut microbiota and to influence the circulating levels of LPS [19]. However, we did not intend to review all potential and nutritional factors that might increase levels of LPS and prefer to limit our hypothesis to lipids, which is a well-known risk factor for AD [77].…”

Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration

“…Bi-directional interactions with microbiota and peripheral metabolism add another layer of complexity to the metabolomic status. For instance, polyphenols and ω-3 PUFAs may be beneficial to neurons through the stimulation of a healthy GM, which may further enhance their effect by generating nutrient-derived metabolites [ 377 , 378 ]. Meng et al used systemic nutrigenomics to elucidate how ω-3 PUFAs counteract the harmful effects of fructose in brain rats [ 379 ], providing rational support for targeted dietary interventions in humans.…”

Functional Foods: An Approach to Modulate Molecular Mechanisms of Alzheimer’s Disease

“…If the interaction between nutrients (micro and macro) and microbiota is very tight, such a relation essentially concerns polyphenols [312]. Polyphenols are a large family of natural compounds produced by plants endowed with scavenging protective properties against the oxidative stress and/or inflammatory signaling occurring in the brain during neurodegeneration.…”

“…As known (see above, Section 2.1), the bioavailability of this group of compounds is poor-due to low absorption and fast metabolism leading to their rapid elimination from the organism-however, gut microbiota metabolizes them into active and bioavailable metabolites. This is an interesting aspect of the issue; in fact, it is suggested that the composition of bacteria is a key element in the response to polyphenol treatment and that gut microbiota are probably responsible for polyphenols health effects by regulating their bioavailability [312].…”