Neuroinflammation, Gut Microbiome, and Alzheimer’s Disease

The gut brain axis seems to modulate various psychiatric and neurological disorders such as Alzheimer’s disease (AD). Growing evidence has led to the assumption that the gut microbiome might contribute to or even present the nucleus of origin for these diseases. In this regard, modifiers of the microbial composition might provide attractive new therapeutics. Aim of our study was to elucidate the effect of a rigorously changed gut microbiome on pathological hallmarks of AD. 5xFAD model mice were treated by antibiotics or probiotics (L. acidophilus and L. rhamnosus) for 14 weeks. Pathogenesis was measured by nest building capability and plaque deposition. The gut microbiome was affected as expected: antibiotics significantly reduced viable commensals, while probiotics transiently increased Lactobacillaceae. Nesting score, however, was only improved in antibiotics-treated mice. These animals additionally displayed reduced plaque load in the hippocampus. While various physiological parameters were not affected, blood sugar was reduced and serum glucagon level significantly elevated in the antibiotics-treated animals together with a reduction in the receptor for advanced glycation end products RAGE—the inward transporter of Aβ peptides of the brain. Assumedly, the beneficial effect of the antibiotics was based on their anti-diabetic potential.

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Chapter 12. The Role of Gut Microbiome in Alzheimer's Disease and Therapeutic Strategies

10.1039/9781839162732-00354 ◽

2022 ◽

pp. 354-376

Author(s):

Sourav Samanta ◽

Madhu Ramesh ◽

Ashish Kumar ◽

Thimmaiah Govindaraju

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiome ◽

Therapeutic Strategies

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EC-03-04: GUT MICROBIOME ALTERATIONS IN ALZHEIMER'S DISEASE: CLINICAL EVIDENCE AND THE WAY FORWARD

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.2768 ◽

2006 ◽

Vol 14 (7S_Part_18) ◽

pp. P1007-P1007

Author(s):

Giovanni B. Frisoni

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiome ◽

Clinical Evidence ◽

The Way

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The gut microbiome dysbiosis and inflammation-driven pathogenesis of Alzheimer's disease animal model

IBRO Reports ◽

10.1016/j.ibror.2019.07.740 ◽

2019 ◽

Vol 6 ◽

pp. S237

Author(s):

Sang Tae Kim ◽

Sangyun Kim

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Model ◽

Gut Microbiome

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The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer’s Disease—a Critical Review

Molecular Neurobiology ◽

10.1007/s12035-018-1188-4 ◽

2018 ◽

Vol 56 (3) ◽

pp. 1841-1851 ◽

Cited By ~ 79

Author(s):

Marta Sochocka ◽

Katarzyna Donskow-Łysoniewska ◽

Breno Satler Diniz ◽

Donata Kurpas ◽

Ewa Brzozowska ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiome ◽

Critical Review

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Brain Aging and Gut–Brain Axis

Nutrients ◽

10.3390/nu11020424 ◽

2019 ◽

Vol 11 (2) ◽

pp. 424 ◽

Cited By ~ 1

Author(s):

M. Mohajeri

Keyword(s):

Multiple Sclerosis ◽

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Brain Development ◽

Neurodegenerative Disorders ◽

Gut Microbiome ◽

Brain Aging ◽

And Function

In the last decade, the microbiome in general and the gut microbiome in particular have been associated not only to brain development and function, but also to the pathophysiology of brain aging and to neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), depression, or multiple sclerosis (MS) [...]

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Reducing the Search Space in Literature-Based Discovery by Exploring Outlier Documents: a Case Study in Finding Links Between Gut Microbiome and Alzheimer’s Disease

Genomics and Computational Biology ◽

10.18547/gcb.2017.vol3.iss3.e58 ◽

2017 ◽

Vol 3 (3) ◽

pp. 58 ◽

Cited By ~ 4

Author(s):

Bojan Cestnik ◽

Elsa Fabbretti ◽

Donatella Gubiani ◽

Tanja Urbančič ◽

Nada Lavrač

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiome ◽

Domain Knowledge ◽

Search Space ◽

Easy Access ◽

Literature Mining ◽

Cross Domain ◽

Scientific Papers ◽

Literature Based Discovery

Literature-based discovery tools have been often used to overcome the problem of fragmentation of science and to assist researchers in their process of cross-domain knowledge discovery. In this paper we propose a methodology for cross-domain literature-based discovery that focuses on outlier documents to reduce the search space of potential cross-domain links and to improve search efficiency. In a previous study, literature mining tools OntoGen for document clustering and CrossBee for cross-domain bridging term exploration were combined to search for hidden relations in scientific papers from two different domains of interest, where the utility of the approach was demonstrated in a study involving PubMed papers about Alzheimer’s disease and gut microbiome. This paper extends the approach by proposing a methodology, implemented as a repeatable workflow in a web-based text mining platform TextFlows, which enables easy access and execution of the methodology for the interested researcher.

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Enhancement of Insulin/PI3K/Akt Signaling Pathway and Modulation of Gut Microbiome by Probiotics Fermentation Technology, a Kefir Grain Product, in Sporadic Alzheimer’s Disease Model in Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2021.666502 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nesrine S. El Sayed ◽

Esraa A. Kandil ◽

Mamdooh H. Ghoneum

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Insulin Receptor ◽

Insulin Signaling ◽

Gut Microbiome ◽

Akt Signaling ◽

Sporadic Alzheimer’S Disease ◽

Gsk 3Β ◽

Fermentation Technology

Sporadic Alzheimer’s disease (AD) is the most common neurodegenerative disorder with cognitive dysfunction. Remarkably, alteration in the gut microbiome and resultant insulin resistance has been shown to be connected to metabolic syndrome, the crucial risk factor for AD, and also to be implicated in AD pathogenesis. Thus, this study, we assessed the efficiency of probiotics fermentation technology (PFT), a kefir product, in enhancing insulin signaling via modulation of gut microbiota to halt the development of AD. We also compared its effectiveness to that of pioglitazone, an insulin sensitizer that has been confirmed to substantially treat AD. AD was induced in mice by a single injection of intracerebroventricular streptozotocin (STZ; 3 mg/kg). PFT (100, 200, 400 mg/kg) and pioglitazone (30 mg/kg) were administered orally for 3 weeks. Behavioral tests were conducted to assess cognitive function, and hippocampal levels of acetylcholine (Ach) and β-amyloid (Aβ1–42) protein were assessed along with histological examination. Moreover, the expression of the insulin receptor, insulin degrading enzyme (IDE), and the phosphorylated forms of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), mammalian target of rapamycin (mTOR), and tau were detected. Furthermore, oxidative stress and inflammatory biomarkers were estimated. Treatment with PFT reversed STZ-induced neurodegeneration and cognitive impairment, enhanced hippocampal Ach levels, and reduced Aβ1–42 levels after restoration of IDE activity. PFT also improved insulin signaling, as evidenced by upregulation of insulin receptor expression and activation of PI3K/Akt signaling with subsequent suppression of GSK-3β and mTOR signaling, which result in the downregulation of hyperphosphorylated tau. Moreover, PFT significantly diminished oxidative stress and inflammation induced by STZ. These potential effects were parallel to those produced by pioglitazone. Therefore, PFT targets multiple mechanisms incorporated in the pathogenesis of AD and hence might be a beneficial therapy for AD.

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Differences in Gut Microbiota as a Potential Factor in Alzheimer’s Disease Development

Journal of Student Research ◽

10.47611/jsrhs.v10i3.1609 ◽

2021 ◽

Vol 10 (3) ◽

Author(s):

Briya Patel ◽

Leya Joykutty

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiome ◽

Disease Development ◽

Gamma Aminobutyric Acid ◽

Human Species ◽

Microbiome Composition ◽

Potential Factor ◽

The Impact ◽

The Brain

Considering that humans consist of more non-human species than cells, it is critical to understand the impact of the microbiome on diseases. As Alzheimer’s disease becomes a more and more pressing issue, it may be possible to combat it or slow its progress by understanding how alterations in the gut microbiome, which can influence functions in the brain in a variety of ways, affect its development.Gut bacteria can produce neurotransmitters such as melatonin, gamma-aminobutyric acid, histamine, and acetylcholine, which can contribute or antagonize neuroinflammation and neurofibrillary tangles. It is best to balance beneficial bacteria with harmful bacteria. Additionally, using probiotics and altered diets can serve to change gut microbiome composition and influence Alzheimer’s disease development. It is important to understand microbiome-cell interactions and utilize that information to create new therapeutic strategies for Alzheimer’s disease through forms like diets, probiotics, and interventional procedures.

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