Recent Nutrients The study explored the existing literature to better understand whether dietary modification and changes in the gut microbial population could influence the disease course of Alzheimer’s and Parkinson’s diseases.
Study: The role of gut microbiota and diet as regulatory factors in the course of Alzheimer’s and Parkinson’s disease. Image credit: TopMicrobialStock/Shutterstock.com
The effect of gut microflora on the central nervous system
The human gut contains hundreds of bacteria associated with the host’s physiological functions and immunity. Bacterial populations in the gastrointestinal tract increase from the stomach to the large intestine.
Some common bacteria in the human gut are Firmicutes, Bacteroidetes, Proteobacteriaand Actinobacteria.
Previous studies have shown the prevalence of heterogeneity in gut microbial composition and abundance among humans.
This heterogeneity has been associated with many factors including diet, medications, hormones, physical activity, antibiotics, age, and exposure to toxic substances.
A healthy gut microbiome maintains body homeostasis by improving gut barrier integrity and metabolizing nutrients from food, drugs and xenobiotics.
These microbes also produce short-chain fatty acids (SCFAs) that are responsible for reducing systemic inflammation.
A change in the microbial composition and abundance of the human gut has been associated with the onset of obesity, diabetes, hypertension, colon cancer, non-alcoholic steatohepatitis and Crohn’s disease.
Many studies have also documented evidence of how gut microflora affects the human nervous system and psyche.
The gut microbiota interacts bidirectionally with the central nervous system (CNS) through the gut-brain axis. Mechanistically, certain members of the gut microbiota produce neurotransmitters, such as catecholamines, acetylcholine, serotonin, gamma-aminobutyric acid, and histamine, which influence the gut-brain axis.
Other mechanisms by which gut microbiota affect the CNS are the regulation of immune system activity, effects on tryptophan metabolism, changes in microbiota composition, and the synthesis of specific metabolites.
Gastrointestinal functions are regulated by the enteric nervous system (ENS) through direct or indirect mechanisms linked to sympathetic and parasympathetic signaling.
Enteroendocrine cells receive signals from the gut microflora to activate the synthesis of circulating hormones, which can enter the blood-brain barrier (BBB) and affect CNS cells.
Gut microbial dysbiosis results in enhanced intestinal permeability and a pro-inflammatory state.
A leaky gut or damaged intestinal barrier function causes uncontrolled passage of inflammatory agents, bacterial components and toxic metabolites that can cause systemic inflammation.
Inflammatory mediators could lead to activation of cytokine production in the brain, causing neuroinflammation.
Gut microbiota in neurodegenerative diseases
The effect of gut microbes on the development of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, has been discussed in many studies.
Gut bacteria synthesize multiple metabolites, such as trimethylamine N-oxide (TMAO), amyloid curli, SCFAs, secondary bile acids (BAs) and lipopolysaccharides (LPS), which are associated with immunological and metabolic changes leading to progression of neurodegenerative disease.
Heterogeneity in gut microbial composition was noted in this study. For example, stool samples from patients with Parkinson’s disease were analyzed and showed increased abundance Bacteroides and Akkermansia Muciniphilaand decrease in Actinobacteria, Firmicutes Faecalibacteriumand Roseburia was observed.
Several studies have shown that TMAO significantly accelerates the conformational change of proteins from random Aβ coil to beta sheet. The concentration of TMAO in the cerebrospinal fluid was higher in people with Alzheimer’s and Parkinson’s disease.
Bile acids can alter the gut microbiota through cytotoxic effects on certain bacterial species. These can also activate carbonic anhydrase 12 (CAR12), nitric oxide synthase (iNOS), and interleukin-18 (IL-18), which are associated with bacterial overgrowth.
Therefore, excess bile acids could lead to dysbiosis of the gut microbiome. One study showed that in Alzheimer’s patients, the concentration of primary bile acids was lower than in healthy subjects.
In contrast, the concentration of secondary bile acids was higher in Alzheimer’s disease patients than in healthy subjects.
LPS synthesized by the gut microbe can penetrate the CNS and upregulate receptors on microglial cells.
Activation of microglial receptors TLR2 and TLR4 induces the production of proinflammatory interleukin-IL-22 and interleukin-IL17A, which induces neuroinflammation. A prolonged state of neuroinflammation can lead to the development of neurodegenerative diseases.
The effect of nutrition on neurodegenerative diseases
Patients with neurodegenerative diseases can benefit from an adapted diet. For example, a certain diet can reduce inflammation and its consequences, namely impaired neuronal function, in patients with Parkinson’s and Alzheimer’s disease.
The ketogenic diet (KD), the Mediterranean intervention DASH diet for neurodegenerative delay (MIND), and the Dietary Approaches to Stop Hypertension (DASH) diet have a positive impact on the course of neurodegenerative diseases.
Compared to different diets, KD has shown a greater effect on neurodegenerative diseases.
This diet is associated with increased fat consumption and reduced carbohydrate intake. KD increased the production of ketone bodies, which exert their anti-inflammatory effects by reducing monocyte chemoattractant protein (CCL2/MCP-1) levels and inhibiting NF-kB. Ketone bodies also have a preventive effect on dopaminergic neurons and tau protein hyperphosphorylation.
In addition, they are also associated with positive cognitive functions, such as memory and attention. However, it should be noted that KD reduces the diversity of bacterial species, which is a major drawback of this diet.
The Mediterranean diet is also associated with numerous anti-inflammatory effects due to the diet’s high content of vitamins, omega-3 fatty acids (o3-PUFA), polyphenols and carotenoids. These ingredients prevent many cognitive disorders and dementia.
Combined, dietary intervention with appropriate gut microbial composition and diversity could positively influence the course of Alzheimer’s and Parkinson’s disease.
