scholarly journals Bile Acids as Key Modulators of the Brain-Gut-Microbiota Axis in Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Agata Mulak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Microbiota Composition ◽  
Dietary Interventions ◽  
Age Related ◽  
Host Metabolism ◽  
The Brain ◽  
Gut Microbiota Composition

Recently, the concept of the brain-gut-microbiota (BGM) axis disturbances in the pathogenesis of Alzheimer’s disease (AD) has been receiving growing attention. At the same time, accumulating data revealing complex interplay between bile acids (BAs), gut microbiota, and host metabolism have shed new light on a potential impact of BAs on the BGM axis. The crosstalk between BAs and gut microbiota is based on reciprocal interactions since microbiota determines BA metabolism, while BAs affect gut microbiota composition. Secondary BAs as microbe-derived neuroactive molecules may affect each of three main routes through which interactions within the BGM axis occur including neural, immune, and neuroendocrine pathways. BAs participate in the regulation of multiple gut-derived molecule release since their receptors are expressed on various cells. The presence of BAs and their receptors in the brain implies a direct effect of BAs on the regulation of neurological functions. Experimental and clinical data confirm that disturbances in BA signaling are present in the course of AD. Disturbed ratio of primary to secondary BAs as well as alterations in BA concertation in serum and brain samples have been reported. An age-related shift in the gut microbiota composition associated with its decreased diversity and stability observed in AD patients may significantly affect BA metabolism and signaling. Given recent evidence on BA neuroprotective and anti-inflammatory effects, new therapeutic targets have been explored including gut microbiota modulation by probiotics and dietary interventions, ursodeoxycholic acid supplementation, and use of BA receptor agonists.

scholarly journals Gut Microbiota and Dysbiosis in Alzheimer’s Disease: Implications for Pathogenesis and Treatment

2020 ◽  
Vol 57 (12) ◽  
pp. 5026-5043 ◽  
Author(s):  
Shan Liu ◽  
Jiguo Gao ◽  
Mingqin Zhu ◽  
Kangding Liu ◽  
Hong-Liang Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Gut Dysbiosis ◽  
Bidirectional Communication ◽  
Significant Research ◽  
Novel Therapeutic Strategies ◽  
The Brain ◽  
Brain Homeostasis ◽  
Gut Microbiota Composition

Abstract Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term “microbiota-gut-brain axis” from “gut-brain axis” underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer’s disease (AD). Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.

scholarly journals Associations between gut microbiota and Alzheimer’s disease, major depressive disorder, and schizophrenia

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Zhenhuang Zhuang ◽  
Ruotong Yang ◽  
Wenxiu Wang ◽  
Lu Qi ◽  
Tao Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Major Depressive Disorder ◽  
Gut Microbiota ◽  
Depressive Disorder ◽  
Lower Risk ◽  
Neuropsychiatric Disorders ◽  
Microbiota Composition ◽  
Major Depressive ◽  
Gut Microbiota Composition

Abstract Background Growing evidence has shown that alterations in the gut microbiota composition were associated with a variety of neuropsychiatric conditions. However, whether such associations reflect causality remains unknown. We aimed to reveal the causal relationships among gut microbiota, metabolites, and neuropsychiatric disorders including Alzheimer’s disease (AD), major depressive disorder (MDD), and schizophrenia (SCZ). Methods A two-sample bi-directional Mendelian randomization analysis was performed by using genetic variants from genome-wide association studies as instrumental variables for gut microbiota, metabolites, AD, MDD, and SCZ, respectively. Results We found suggestive associations of host-genetic-driven increase in Blautia (OR, 0.88; 95%CI, 0.79–0.99; P = 0.028) and elevated γ-aminobutyric acid (GABA) (0.96; 0.92–1.00; P = 0.034), a downstream product of Blautia-dependent arginine metabolism, with a lower risk of AD. Genetically increased Enterobacteriaceae family and Enterobacteriales order were potentially associated with a higher risk of SCZ (1.09; 1.00–1.18; P = 0.048), while Gammaproteobacteria class (0.90; 0.83–0.98; P = 0.011) was related to a lower risk for SCZ. Gut production of serotonin was potentially associated with an increased risk of SCZ (1.07; 1.00–1.15; P = 0.047). Furthermore, genetically increased Bacilli class was related to a higher risk of MDD (1.07; 1.02–1.12; P = 0.010). In the other direction, neuropsychiatric disorders altered gut microbiota composition. Conclusions These data for the first time provide evidence of potential causal links between gut microbiome and AD, MDD, and SCZ. GABA and serotonin may play an important role in gut microbiota-host crosstalk in AD and SCZ, respectively. Further investigations in understanding the underlying mechanisms of associations between gut microbiota and AD, MDD, and SCZ are required.

scholarly journals Shifts in gut microbiota composition in an APP/PSS1 transgenic mouse model of Alzheimer's disease during lifespan

2018 ◽  
Vol 66 (6) ◽  
pp. 464-471 ◽  
Author(s):  
C. Bäuerl ◽  
M.C. Collado ◽  
A. Diaz Cuevas ◽  
J. Viña ◽  
G. Pérez Martínez
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Microbiota Composition ◽  
Model Of Alzheimer’S Disease ◽  
Gut Microbiota Composition

scholarly journals Probable Causes of Alzheimer’s Disease

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 16
Author(s):  
James David Adams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lactic Acid ◽  
Blood Brain Barrier ◽  
Transient Receptor Potential ◽  
Brain Barrier ◽  
Folate Intake ◽  
Blood Brain ◽  
Age Related ◽  
The Brain

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

A Crucial Role for Diet in the Relationship Between Gut Microbiota and Cardiometabolic Disease

2020 ◽  
Vol 71 (1) ◽  
pp. 149-161 ◽  
Author(s):  
Ilias Attaye ◽  
Sara-Joan Pinto-Sietsma ◽  
Hilde Herrema ◽  
Max Nieuwdorp
Keyword(s):  
Gut Microbiota ◽  
Global Scale ◽  
Cardiometabolic Disease ◽  
Microbiota Composition ◽  
Dietary Interventions ◽  
Fermentable Carbohydrates ◽  
Cost Efficient ◽  
And Function ◽  
Gut Microbiota Composition

Cardiometabolic disease (CMD), such as type 2 diabetes mellitus and cardiovascular disease, contributes significantly to morbidity and mortality on a global scale. The gut microbiota has emerged as a potential target to beneficially modulate CMD risk, possibly via dietary interventions. Dietary interventions have been shown to considerably alter gut microbiota composition and function. Moreover, several diet-derived microbial metabolites are able to modulate human metabolism and thereby alter CMD risk. Dietary interventions that affect gut microbiota composition and function are therefore a promising, novel, and cost-efficient method to reduce CMD risk. Studies suggest that fermentable carbohydrates can beneficially alter gut microbiota composition and function, whereas high animal protein and high fat intake negatively impact gut microbiota function and composition. This review focuses on the role of macronutrients (i.e., carbohydrate, protein, and fat) and dietary patterns (e.g., vegetarian/vegan and Mediterranean diet) in gut microbiota composition and function in the context of CMD.

scholarly journals Relationship between Wine Consumption, Diet and Microbiome Modulation in Alzheimer’s Disease

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3082
Author(s):  
M. Victoria Moreno-Arribas ◽  
Begoña Bartolomé ◽  
José L. Peñalvo ◽  
Patricia Pérez-Matute ◽  
Maria José Motilva
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Intestinal Microbiome ◽  
Dietary Polyphenols ◽  
Age Related ◽  
Wine Polyphenols ◽  
The Impact

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to the most common form of dementia in elderly people. Modifiable dietary and lifestyle factors could either accelerate or ameliorate the aging process and the risk of developing AD and other age-related morbidities. Emerging evidence also reports a potential link between oral and gut microbiota alterations and AD. Dietary polyphenols, in particular wine polyphenols, are a major diver of oral and gut microbiota composition and function. Consequently, wine polyphenols health effects, mediated as a function of the individual’s oral and gut microbiome are considered one of the recent greatest challenges in the field of neurodegenerative diseases as a promising strategy to prevent or slow down AD progression. This review highlights current knowledge on the link of oral and intestinal microbiome and the interaction between wine polyphenols and microbiota in the context of AD. Furthermore, the extent to which mechanisms bacteria and polyphenols and its microbial metabolites exert their action on communication pathways between the brain and the microbiota, as well as the impact of the molecular mediators to these interactions on AD patients, are described.

scholarly journals Osmotin-loaded magnetic nanoparticles with electromagnetic guidance for the treatment of Alzheimer's disease

Nanoscale ◽  
2017 ◽  
Vol 9 (30) ◽  
pp. 10619-10632 ◽  
Author(s):  
Faiz Ul Amin ◽  
Ali Kafash Hoshiar ◽  
Ton Duc Do ◽  
Yeongil Noh ◽  
Shahid Ali Shah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Nanoparticles ◽  
Neurodegenerative Disease ◽  
Amyloid Beta ◽  
Age Related ◽  
Electromagnetic Guidance ◽  
The Brain

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain.

scholarly journals Elevated age-related cortical iron, ferritin and amyloid plaques in APPswe/PS1ΔE9 transgenic mouse model of Alzheimer’s disease

2019 ◽  
pp. S445-S451 ◽  
Author(s):  
H. Svobodová ◽  
D. Kosnáč ◽  
Z. Balázsiová ◽  
H. Tanila ◽  
P.O. Miettinen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaques ◽  
Amyloid Plaque ◽  
Free Iron ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Concentration Changes ◽  
The Brain ◽  
Important Marker

Iron is very important element for functioning of the brain. Its concentration changes with aging the brain or during disease. The aim of our work was the histological examination of content of ferritin and free iron (unbound) in brain cortex in association with Aβ plaques from their earliest stages of accumulation in amyloid plaque forming APP/PS1 transgenic mice. Light microscopy revealed the onset of plaques formation at 8-monthage. Detectable traces of free iron and no ferritin were found around plaques at this age, while the rate of their accumulation in and around Aβ plaques was elevated at 13 months of age. Ferritin accumulated mainly on the edge of Aβ plaques, while the smaller amount of free iron was observed in the plaque-free tissue, as well as in and around Aβ plaques. We conclude that free iron and ferritin accumulation follows the amyloid plaques formation. Quantification of cortical iron and ferritin content can be an important marker in the diagnosis of Alzheimer’s disease.

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