Gut microbiota in Alzheimer’s disease: Understanding molecular pathways and potential therapeutic perspectives

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: 104, P. 102659 - 102659

Published: Jan. 10, 2025

Language: Английский

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Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer’s disease continuum

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: Feb. 1, 2025

Gut microbiota dysbiosis is linked to Alzheimer's disease (AD), but our understanding of the molecular and neuropathological bases underlying such association remains fragmentary. Using 16S rDNA amplicon sequencing, untargeted metabolomics, multi-modal magnetic resonance imaging, we examined group differences in gut microbiome, fecal metabolome, neuroimaging measures, cognitive variables across 30 patients with AD, 75 individuals mild impairment (MCI), 61 healthy controls (HC). Furthermore, assessed associations between these multi-omics changes using correlation mediation analyses. There were significant microbial composition, which driven by 8 taxa (e.g., Staphylococcus Bacillus) exhibiting a progressive increase relative abundance from HC MCI 2 Anaerostipes) showing gradual decrease. 26 metabolites Arachidonic, Adrenic, Lithocholic acids) exhibited AD. We also observed gray matter atrophy broadly distributed regions micro-structural integrity damage widespread white tracts along AD continuum. Integration revealed microbiota, metabolites, neuroimaging, cognition. More importantly, identified two potential pathways: (1) → cognition, (2) Aside elucidating mechanism whereby findings may contribute groundwork for future interventions targeting microbiota-metabolites-brain-cognition pathways as therapeutic strategy

Language: Английский

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Bridging gap in the treatment of Alzheimer’s disease via postbiotics: Current practices and future prospects

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102689 - 102689

Published: Feb. 1, 2025

Language: Английский

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Exploring the microbiota-gut-brain axis: impact on brain structure and function

Frontiers in Neuroanatomy, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 12, 2025

The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. MGBA serves as conduit between CNS ENS, facilitating communication emotional cognitive centers via diverse pathways. In initial stages this review, we will examine way how affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, blood barrier (BBB) permeability, synaptic structure. Furthermore, review potential mechanistic pathways neuroplasticity through influence. short-chain fatty acids (SCFAs) play pivotal MGBA, where they can modify BBB. We therefore discuss SCFAs influence microglia, neuronal, astrocyte function, well their disorders such Alzheimer’s disease (AD), Parkinson’s (PD). Subsequently, technical strategies employed to study interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), antibiotics-induced dysbiosis. Finally, particular bacterial strains affect By gaining deeper understanding it may be possible facilitate research into microbial-based pharmacological interventions therapeutic for neurological diseases.

Language: Английский

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Transmission of Alzheimer’s disease-associated microbiota dysbiosis and its impact on cognitive function: evidence from mice and patients

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(10), P. 4421 - 4437

Published: Aug. 21, 2023

Language: Английский

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The gut microbiome regulates astrocyte reaction to Aβ amyloidosis through microglial dependent and independent mechanisms

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: July 6, 2023

Abstract Background Previous studies show that antibiotic-mediated (abx) alteration of the gut microbiome (GMB) results in a reduction amyloid beta (Aβ) plaques and proinflammatory microglial phenotype male APPPS1-21 mice. However, effect GMB perturbation on astrocyte phenotypes microglial-astrocyte communication context amyloidosis has not been examined. Methods To study whether modulates amyloidosis, female mice were treated with broad-spectrum abx leading to perturbation. GFAP + astrocytes, plaque-associated astrocytes (PAA), PAA morphological parameters, complement component C3 levels quantified using combination immunohistochemistry, immunoblotting, widefield microscopy, confocal microscopy. Furthermore, these same assessed abx-treated received either fecal matter transplant (FMT) from untreated donors restore their or vehicle control. assess complete absence phenotypes, raised germ-free (GF) specific-pathogen free conditions (SPF). Lastly, we microglia are necessary for abx-induced by depleting via treatment colony-stimulating factor 1 receptor (CSF1R) inhibitor (PLX5622) control PLX5622 abx. Results Herein, demonstrate postnatal reduces reactive PAAs, suggesting plays role regulating induction recruitment Aβ plaques. Additionally, compared controls, PAAs exhibit an altered morphology increased number length processes reduced astrocytic C3, consistent homeostatic phenotype. reduction, changes, restored when subject FMT donor Next, found GF have similar as Correlational analysis revealed pathogenic bacteria depleted correlate astrocytosis, changes. Finally, determined abx-mediated expression is independent microglia. alterations dependent presence microglia, there both phenotypes. Conclusions We first time, important controlling induction, morphology, regulation

Language: Английский

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Gut microbiota-host lipid crosstalk in Alzheimer’s disease: implications for disease progression and therapeutics

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: April 16, 2024

Abstract Trillions of intestinal bacteria in the human body undergo dynamic transformations response to physiological and pathological changes. Alterations their composition metabolites collectively contribute progression Alzheimer’s disease. The role gut microbiota disease is diverse complex, evidence suggests lipid metabolism may be one potential pathways. However, mechanisms that mediate pathology remain unclear, necessitating further investigation for clarification. This review highlights current understanding how disrupts discusses implications these discoveries guiding strategies prevention or treatment based on existing data.

Language: Английский

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Taming neuroinflammation in Alzheimer's disease: The protective role of phytochemicals through the gut−brain axis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117277 - 117277

Published: Aug. 9, 2024

Language: Английский

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Alzheimer’s Disease: Models and Molecular Mechanisms Informing Disease and Treatments

Bioengineering, Journal Year: 2024, Volume and Issue: 11(1), P. 45 - 45

Published: Jan. 1, 2024

Alzheimer’s Disease (AD) is a complex neurodegenerative disease resulting in progressive loss of memory, language and motor abilities caused by cortical hippocampal degeneration. This review captures the landscape understanding AD pathology, diagnostics, current therapies. Two major mechanisms direct pathology: (1) accumulation amyloid β (Aβ) plaque (2) tau-derived neurofibrillary tangles (NFT). The most common variants Aβ pathway APP, PSEN1, PSEN2 are largely responsible for early-onset (EOAD), while MAPT, APOE, TREM2 ABCA7 have modifying effect on late-onset (LOAD). More recent studies implicate chaperone proteins degrading AD. Several tests, such as cognitive function, brain imaging, cerebral spinal fluid (CSF) blood used diagnosis. Additionally, several biomarkers seem to unique specific combination expression could potentially be improved, less invasive diagnostics. In addition genetic perturbations, environmental influences, altered gut microbiome signatures, affect Effective treatments been challenging develop. Currently, there FDA approved drugs (cholinesterase inhibitors, Aß-targeting antibodies an NMDA antagonist) that mitigate rate decline symptoms distress.

Language: Английский

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Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review

Molecules, Journal Year: 2024, Volume and Issue: 29(12), P. 2812 - 2812

Published: June 13, 2024

Tau protein is a microtubule-associated that widely distributed in the central nervous system and maintains regulates neuronal morphology function. aggregates abnormally forms neurofibrillary tangles neurodegenerative diseases, disrupting structure function of neurons leading to death, which triggers initiation progression neurological disorders. The aggregation tau diseases associated with post-translational modifications, may affect hydrophilicity, spatial conformation, stability protein, promoting formation tangles. Therefore, studying role mechanism aberrant important for understanding finding therapeutic approaches. This review describes possible mechanisms by promotes modifications influencing factors, current status drug discovery development related contribute new approaches alleviate or treat diseases.

Language: Английский

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