Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease

Kesika, Periyanaina; Suganthy, Natarajan; Sivamaruthi, Bhagavathi Sundaram; Chaiyasut, Chaiyavat

doi:10.1016/j.lfs.2020.118627

Cited by 303 publications

(216 citation statements)

References 105 publications

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“…Dysbiosis affects the synthesis of signaling proteins that influence metabolic processes related to AD progression [15]. Aging alters the GM composition (high abundance of pro-inflammatory bacteria than anti-inflammatory bacteria) and induces local systematic inflammation that causes impairment in the permeability of the GIT and blood-brain barrier function [3]. Peptostreptococcaceae, Clostridiaceae, Bifidobacteriaceae, Turicibacteraceae, Mogibacteriaceae, and Ruminococcaceae families were found to be less abundant as compared to Bacteroidaceae, Gemellaceae, and Rikenellaceae families in AD participants [75].…”

Section: Gm Dysbiosis and Admentioning

confidence: 99%

“…About 95% of the symbiotic microorganisms of the human microbiome reside in the gut [1]. Intricate ecological colonies of microorganisms dwell in the GIT and are collectively known as the gut microbiota (GM) [2,3]. The GM comprises mainly bacteria, fungi, bacteriophages, archaea, protozoa, and eukaryotic viruses and about 100 trillion microorganisms are harbored in the human GIT [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…The GM is involved in metabolic processes and defense mechanisms and represents a dynamic and diverse population which impacts on the health and disease of the host. The GM develops the immune system in the intestinal mucosa and protects the host from carcinogens by releasing short-chain fatty acids (SCFA) [3]. Alterations of the GM community are referred to as dysbiosis [4,10], and these can lead to metabolic disorders.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, metabolic syndromes and gut dysbiosis also contribute to Alzheimer's disease (AD) and effect memory, learning, and hippocampal plasticity [16]. Diet, probiotics, and other therapeutic strategies have positive effects on GM modulation that may be helpful in the treatment of AD, as these factors alter the composition of the GM and have a positive impact on the host, improving the health status of the gut and body overall [3]. This review summarizes the role of GM dysbiosis, microbial metabolites, and metabolic impairment in AD.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

et al. 2021

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The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

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Section: Gm Dysbiosis and Admentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

et al. 2021

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“…This concept is related to the existence of the so-called “gut-brain-microbiota axis”. Therefore, there are speculations about the possibility of modulating this axis for prophylactic and perhaps even therapeutic purposes for AD disease [ 6 , 60 ]. The correlation between the gut and the brain may be based on, among other things, the interaction via specific and non-specific chemical compounds produced by the gut flora that cross the blood–brain barrier (BBB).…”

Section: Intestinal Microbiota and Alzheimer’s Diseasementioning

confidence: 99%

Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

Miziak

Błaszczyk²,

Czuczwar

2021

Pharmaceuticals

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Alzheimer’s disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. The PUBMED, Medical Subject Heading and Clinical Trials databases were used for searching relevant data. Novel treatments are focused on already approved drugs for other conditions and also searching for innovative drugs encompassing investigational compounds. Among the approved drugs, we investigated, are intranasal insulin (and other antidiabetic drugs: liraglitude, pioglitazone and metformin), bexarotene (an anti-cancer drug and a retinoid X receptor agonist) or antidepressant drugs (citalopram, escitalopram, sertraline, mirtazapine). The latter, especially when combined with antipsychotics (for instance quetiapine or risperidone), were shown to reduce neuropsychiatric symptoms in AD patients. The former enhanced cognition. Procognitive effects may be also expected with dietary antioxidative and anti-inflammatory supplements—curcumin, myricetin, and resveratrol. Considering a close relationship between brain ischemia and AD, they may also reduce post-brain ischemia neurodegeneration. An investigational compound, CN-105 (a lipoprotein E agonist), has a very good profile in AD preclinical studies, and its clinical trial for postoperative dementia is starting soon.

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Development of a Clinical Risk Score Prediction Tool for 5-, 9-, and 13-Year Risk of Dementia

et al. 2022

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ImportanceAlthough researchers have devoted substantial efforts, money, and time to studying the causes of dementia and the means to prevent it, no effective treatment exists yet. Identifying preclinical risk factors of dementia could help prevent or delay its progression.ObjectiveTo develop a point risk score prediction model of dementia.Design, Setting, and ParticipantsThis study used a large UK population-based prospective cohort study conducted between March 13, 2006, and October 1, 2010. Data analysis was performed from June 7 to September 15, 2021. Individual analyses of time end points were concluded at the first dementia diagnosis during the follow-up period. The data were split into training and testing data sets to separately establish and validate a prediction model.Main Outcomes and MeasuresOutcomes of interest included 5-, 9-, and 13-year dementia risk. Least absolute shrinkage and selection operator and multivariate Cox proportional hazards regression models were used to identify available and practical dementia predictors. A point risk score model was developed for the individual prediction of 5-, 9-, and 13-year dementia risk.ResultsA total of 502 505 participants were selected; the population after exclusions for missing data and dementia diagnosis at baseline was 444 695 (205 187 men; mean [SD] age, 56.74 [8.18] years; 239 508 women; mean [SD] age, 56.20 [8.01] years). Dementia occurrence during the 13 years of follow-up was 0.7% for men and 0.5% for women. The C statistic of the final multivariate Cox proportional hazards regression model was 0.86 for men and 0.85 for women in the training data set, and 0.85 for men and 0.87 for women in the testing data set. Men and women shared some modifiable risk and protective factors, but they also presented independent risk factors that accounted for 31.7% of men developing dementia and 53.35% of women developing dementia according to the weighted population-attributable fraction. The total point score of the risk score model ranged from −18 to 30 in men and −17 to 30 in women. The risk score model yielded nearly 100% prediction accuracy of 13-year dementia risk both in men and women.Conclusions and RelevanceIn this diagnostic study, a practical risk score tool was developed for individual prediction of dementia risk, which may help individuals identify their potential risk profile and provide guidance on precise and timely actions to promote dementia delay or prevention.

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Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease

Cited by 303 publications

References 105 publications

Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

Development of a Clinical Risk Score Prediction Tool for 5-, 9-, and 13-Year Risk of Dementia

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