Gut health linked to Alzheimer's disease progression, experts urge dietary shift

In a recent review published in Nutrients, researchers reviewed existing data on the interactions between the gut microbiome, lipids, and Alzheimer’s disease (AD), providing valuable insights to inform AD prevention and management.

Study: Lipids, Gut Microbiota, and the Complex Relationship with Alzheimer’s Disease: A Narrative Review. Image Credit: Atthapon Raksthaput/Shutterstock.com

Background

AD is a chronic neurological illness associated with aging. Modifiable risk factors could lower Alzheimer's disease morbidity and death. Aging causes gut dysbiosis, which results in an increase in pro-inflammatory bacteria and a decrease in anti-inflammatory bacteria, causing neuroinflammation and damage.

The gut-brain microbiota axis (GBMA) has a big influence on neurodegenerative diseases. High consumption of saturated and trans fats increases cortisol release, but low omega-3 polyunsaturated fatty acid (PUFA) consumption has been associated with neurological disorders.

About the review

In the present review, researchers described the interplay between the gut microbiome, dietary lipids, and Alzheimer’s disease.

The Web of Science, Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Medical Literature Analysis and Retrieval System Online (MEDLINE) through PubMed databases were searched for relevant records published in English, Spanish, or Portuguese. Documents that were not specifically concerned with Alzheimer’s disease were excluded.

Alzheimer’s disease and the gut microbiome

The gut microbiota can influence the development and progression of neurodegenerative disorders such as Alzheimer's. The GBMA is a bidirectional communication channel between the digestive tract and the central nervous system (CNS), and it can contribute to Alzheimer's disease (AD) in unbalanced situations.

The CNS regulates gastrointestinal permeability, secretion, mobility, and immunity through autonomic neural networks. The vagal circuits connect the GBMA to the tenth cranial nerve (vagus) via efferent and afferent pathways.

Disruptions in this communication can impact the immune system's capacity to battle infections, avoid chronic inflammation, and keep the CNS healthy. Intestinal dysbiosis contributes to the course of Alzheimer's disease via pathways that promote the creation of amyloid plaques and neuroinflammation.

Healthy gut microbiota can influence behavior by creating monoamines and short-chain fatty acids (SCFAs), including butyrate, gamma-aminobutyric acid (GABA), serotonin, and dopamine, which enhance cognition and memory. Understanding the GBMA is critical for creating novel Alzheimer's disease therapy options.

Dietary lipids and Alzheimer’s disease

Lipids are vital macromolecules in the human body, particularly the brain, with critical functions in cell membranes and signal transmission. Changes in lipid metabolism contribute to Alzheimer's disease because lipid oxidation occurs early in the illness. Elevated amounts of free cholesterol and decreased sphingomyelin in the middle frontal gyrus of Alzheimer's disease patients are connected with membrane oxidative stress, which leads to the disease.

Inadequate cholesterol availability to neurons can impair synaptic plasticity and nerve signal transmission, resulting in tau disease and neurodegeneration.

Specific blood lipids can influence BBB permeability, possibly altering fatty acid and other lipid availability to brain cells. Lipid microdomains, which are membrane structures made up of sphingolipids, cholesterol, and saturated and polyunsaturated fatty acids, play important roles in Alzheimer's disease pathology, including amyloid beta (Aβ) formation and enabling interactions between A, apolipoprotein (APOE), and tau proteins.

Saturated fat consumption is linked to systemic inflammation, as seen by increased oxidative stress, reactive oxygen species (ROS) levels, and pro-inflammatory cytokine production, aggravating neurodegeneration in people with Alzheimer's disease.

The gut microbiome and dietary lipids

Sphingolipids present in wheat, soy, eggs, and dairy are beneficial for intestinal health and play crucial roles in the composition and diversity of the intestinal microbiota. On the contrary, high-fat meals can negatively impact the gut microbiota by encouraging dysbiosis, affecting intestinal permeability, and boosting the number of gram-negative bacteria that generate LPS. These lipids can also mimic LPS effects, causing pro-inflammatory processes and mucus layer weakening.

Dysbiosis is characterized by lowered Lactobacillus and Bacteroides abundance and increased Clostridium abundance. Furthermore, Alzheimer's disease patients had reduced Bifidobacterium, Castellaniella, Roseburia, Erysipelotrichaceae, Lactobacillaceae, Monoglobus, and Tuzzerella numbers.

Western diets high in saturated and trans fatty acids have been linked to an increased risk of Alzheimer's disease and hypercholesterolemia, possibly due to the buildup of oxysterols in the brain.

PUFAs are required for brain growth and function in Alzheimer's disease, and omega-3 supplementation can slow its progression.

Plant-based diets, on the other hand, such as the Mediterranean diet, are advocated as a worldwide healthy dietary pattern due to their anti-inflammatory qualities. These diets include vital functional nutrients that have antioxidant, anti-inflammatory, and free-radical-fighting properties, which benefit gut and brain health.

Conclusions

Based on the review findings, the gut microbiota, lipids, and Alzheimer's disease are all linked, with dietary lipids potentially promoting AD pathogenesis. Fatty acids are crucial to brain inflammation, synaptic plasticity, and memory.

A healthy diet, such as Mediterranean meals rich in monounsaturated and polyunsaturated fats, could help reduce symptoms and enhance intestine health and blood-brain barrier function. Conversely, Western diets rich in saturated and trans fats could accelerate Alzheimer's disease development.

Further research is required to understand brain lipid composition, discover lipid biomarkers, and examine dietary therapies that change the makeup of the gut microbiota.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.