A recent Nutrients study explored the existing literature to understand better whether diet modification and alterations in the intestinal microbial population could impact the disease course of Alzheimer’s and Parkinson’s diseases.
Study: The Role of Intestinal Microbiota and Diet as Modulating Factors in the Course of Alzheimer’s and Parkinson’s Diseases. Image Credit: TopMicrobialStock/Shutterstock.com
The impact of gut microbiota on the central nervous system
The human gut contains hundreds of bacteria linked to host physiological functions and immunity. Bacterial populations in the gastrointestinal tract increase from the stomach to the colon.
Some common bacteria in the human gut are Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria.
Previous studies have shown the prevalence of heterogeneity in gut microbial composition and abundance between people.
This heterogeneity has been associated with multiple factors that include diet, drugs, hormones, physical activity, antibiotics, age, and exposure to toxic substances.
A healthy gut microbe maintains the body’s homeostasis by improving gut-barrier integrity and metabolizing nutritional molecules from food, drugs, and xenobiotics.
These microbes also produce short-chain fatty acids (SCFAs) that are responsible for decreasing systematic inflammation.
An alteration in human gut microbial composition and abundance has been associated with the manifestation of obesity, diabetes, hypertension, colon cancer, non-alcoholic steatohepatitis, and Crohn’s disease.
Many studies have also documented evidence on how gut microbiota influence the human neural system and psyche.
Intestinal microbiota interacts bidirectionally with the central nervous system (CNS) via the gut-brain axis. Mechanistically, some gut microbiota members produce neurotransmitters, such as catecholamines, acetylcholine, serotonin, gamma-aminobutyric acid, and histamine, which influence the gut-brain axis.
Other mechanisms by which gut microbiota impacts the CNS are immune system activity modulation, effects on tryptophan metabolism, alterations in the microbiota’s composition, and the synthesis of specific metabolites.
Gastrointestinal functions are modulated by the enteric nervous system (ENS) via direct or indirect mechanisms linked to sympathetic and parasympathetic signaling.
The enteroendocrine cells receive signals from the gut microbiota to activate the synthesis of circulatory hormones, which can enter the blood–brain barrier (BBB) and impact CNS cells.
Gut microbial dysbiosis results in enhanced intestinal permeability and proinflammatory state.
A leaky gut or damaged intestinal barrier function causes uncontrolled passage of inflammatory factors, bacterial components, and toxic metabolites that might induce systematic inflammation.
The inflammatory mediators could lead to an activation of cytokine production in the brain, causing neuroinflammation.
Gut microbiota in neurodegenerative diseases
The impact 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 immune and metabolic changes that drive neurodegenerative disease progression.
The heterogeneity in gut microbial composition was noted in this study; for instance, fecal samples from Parkinson’s disease patients were analyzed, and they exhibited an increased abundance of Bacteroides and Akkermansia Muciniphila, and a decrease in Actinobacteria, Firmicutes Faecalibacterium, and Roseburia was observed.
Several studies have shown that TMAO significantly accelerates the conformational change of proteins from Aβ random coil to beta-sheet. The concentration of TMAO in cerebrospinal fluid was higher in individuals with Alzheimer’s and Parkinson’s disease.
Bile acids can alter the gut microbiota via 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 linked to bacterial overgrowth.
Therefore, excess of bile acids could lead to gut microbiome dysbiosis. One study has shown that in patients with Alzheimer’s, the concentration of primary bile acids was lower than in healthy individuals.
In contrast, the concentration of secondary bile acids was higher in patients with Alzheimer’s disease than in healthy individuals.
LPS synthesized by gut microbe can penetrate the CNS and modulate receptors on microglial cells.
Activation of microglial TLR2 and TLR4 receptors induces the production of proinflammatory interleukin-IL-22 and interleukin-IL17A, which causes neuroinflammation. A prolonged neuroinflammation state can lead to the development of neurodegenerative diseases.
The effect of diet on neurodegenerative diseases
Patients with neurodegenerative diseases can benefit from a tailored diet. For instance, a specific diet can reduce inflammation and its consequences, i.e., impaired neuronal function, in patients with Parkinson’s and Alzheimer’s diseases.
The ketogenic diet (KD), the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, 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 exerts its anti-inflammatory effects via decreasing the levels of monocyte chemoattractant protein (CCL2/MCP-1) and inhibiting NF-kB. Ketone bodies also have a preventive effect on dopaminergic neurons and hyperphosphorylation of tau protein.
Furthermore, these are also associated with positive cognitive functions, such as memory and attention. However, it must be noted that KD reduces bacterial species diversity, which is a key disadvantage of this diet.
The Mediterranean diet is also associated with numerous anti-inflammatory effects due to a high content of vitamins, omega-3 fatty acids (ω3-PUFA), polyphenols, and carotenoids in the diet. These components prevent many cognitive disorders and dementia.
Combined, dietary intervention with a proper gut microbial composition and diversity could positively affect the course of Alzheimer’s and Parkinson’s diseases.
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