Time‐restricted feeding mitigates Alzheimer's disease‐associated cognitive impairments via a B. pseudolongum‐propionic acid‐FFAR3 axis

iMeta, Journal Year: 2025, Volume and Issue: 4(2)

Published: Feb. 21, 2025

Abstract Time‐restricted feeding (TRF) holds promise for alleviating cognitive decline in aging, albeit the precise mechanism via gut‐brain axis remains elusive. In a clinical trial, we observed, first time, that 4‐month TRF ameliorated impairments among Alzheimer's disease (AD) patients. Experiments 5xFAD mice corroborated gut microbiota‐dependent effect of on mitigating dysfunction, amyloid‐beta deposition, and neuroinflammation. Multi‐omics integration linked Bifidobacterium pseudolongum ( B. ) propionic acid (PA) with key genes AD pathogenesis. Oral supplementation or PA mimicked TRF's protective effects. Positron emission tomography imaging confirmed PA's blood‐brain barrier penetration, while knockdown free fatty receptor 3 (FFAR3) diminished benefits. Notably, observed positive correlation between fecal improved function an cohort, further indicating enhanced production. These findings highlight microbiota‐metabolites‐brain as pivotal benefits, proposing potential therapies.

Language: Английский

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Relationship Between Short-chain Fatty Acids and Parkinson’s Disease: A Review from Pathology to Clinic

Neuroscience Bulletin, Journal Year: 2023, Volume and Issue: 40(4), P. 500 - 516

Published: Sept. 27, 2023

Parkinson's disease (PD) is a complicated neurodegenerative disease, characterized by the accumulation of α-synuclein (α-syn) in Lewy bodies and neurites, massive loss midbrain dopamine neurons. Increasing evidence suggests that gut microbiota microbial metabolites are involved development PD. Among these, short-chain fatty acids (SCFAs), most abundant metabolites, have been proven to play key role brain-gut communication. In this review, we analyze SCFAs pathology PD from multiple dimensions summarize alterations patients as well their correlation with motor non-motor symptoms. Future research should focus on further elucidating neuroinflammation, developing novel strategies employing derivatives treat

Language: Английский

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Epigenetic effects of short-chain fatty acids from the large intestine on host cells

microLife, Journal Year: 2023, Volume and Issue: 4

Published: Jan. 1, 2023

Adult humans harbor at least as many microbial cells eukaryotic ones. The largest compartment of this diverse population, the gut microbiota, encompasses collection bacteria, archaea, viruses, and organisms that populate gastrointestinal tract, represents a complex dynamic ecosystem has been increasingly implicated in health disease. microbiota carries ∼100-to-150-times more genes than human genome is intimately involved development, homeostasis, Of several metabolites have studied, short-chain fatty acids emerge group molecules shape gene expression types by multiple mechanisms, which include DNA methylation changes, histone post-translational modifications, microRNA-mediated silencing. Butyric acid, one most extensively studied acids, reaches higher concentrations colonic lumen, where it provides source energy for healthy colonocytes, its decrease towards bottom crypts, stem reside. lower butyric acid concentration crypts allows undifferentiated cells, such to progress through cell cycle, pointing importance providing them with protective niche. In cancerous metabolize relatively little mostly rely on glycolysis, preferentially acts deacetylase inhibitor, leading decreased proliferation increased apoptosis. A better understanding interface between epigenetic changes promises unravel detail processes occur physiologically part disease, help develop novel biomarkers, identify new therapeutic modalities.

Language: Английский

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Early changes of fecal short‐chain fatty acid levels in patients with mild cognitive impairments

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(11), P. 3657 - 3666

Published: May 5, 2023

Abstract Aims To compare the fecal levels of short‐chain fatty acids (SCFAs) in patients with mild cognitive impairment (MCI) and normal controls (NCs) to examine whether SCFAs could be used as biomarker for identification MCI. relationship between amyloid‐β (Aβ) deposition brain. Methods A cohort 32 MCI patients, 23 Parkinson's disease (PD) 27 NC were recruited our study. Fecal measured using chromatography mass spectrometry. Disease duration, ApoE genotype, body index, constipation, diabetes evaluated. assess impairment, we Mini‐Mental Status Examination (MMSE). brain atrophy, degree medial temporal atrophy (MTA score, Grade 0–4) was by structural MRI. Aβ positron emission tomography 18 F‐florbetapir (FBP) performed seven at time stool sampling 28 an average 12.3 ± 0.4 months from detect quantify Results Compared NC, had significantly lower acetic acid, butyric caproic acid. Among SCFAs, acid best discriminating achieved AUC 0.752 ( p = 0.001, 95% CI: 0.628–0.876), specificity 66.7%, sensitivity 75%. By combining diagnostic improved, reaching 88.9%. better verify performance randomly assigned 60% participants into training dataset 40% testing dataset. Only showed difference these two groups Based on ROC curve. Next, curve evaluated independent test data 61.5% (8 13) MCI, 72.7% 11) identified correctly. Subgroup analysis that reduced group negatively associated cognition‐related regions. Conclusion Reductions observed compared NC. Reduced regions group. Our findings suggest gut metabolite have potential serve early biomarkers distinguishing targets preventing AD.

Language: Английский

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Common Signaling Pathways Involved in Alzheimer’s Disease and Stroke: Two Faces of the Same Coin

Journal of Alzheimer s Disease Reports, Journal Year: 2023, Volume and Issue: 7(1), P. 381 - 398

Published: April 27, 2023

Alzheimer’s disease (AD) and stroke are two interrelated neurodegenerative disorders which the leading cause of death affect neurons in brain central nervous system. Although amyloid-β aggregation, tau hyperphosphorylation, inflammation hallmarks AD, exact origin AD still undefined. Recent enormous fundamental discoveries suggest that amyloid hypothesis has not been proven anti-amyloid therapies remove deposition have yet slowed cognitive decline. However, stroke, mainly ischemic (IS), is caused by an interruption cerebral blood flow. Significant features both disruption neuronal circuitry at different levels cellular signaling, to glial cells brain. Therefore, it necessary find out common molecular mechanisms these diseases understand their etiological connections. Here, we summarized most signaling cascades including autotoxicity, ApoE4, insulin inflammation, mTOR-autophagy, notch microbiota-gut-brain axis, present IS. These targeted pathways reveal a better understanding IS could provide distinguished platform develop improved therapeutics for diseases.

Language: Английский

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The Brain, the Eating Plate, and the Gut Microbiome: Partners in Migraine Pathogenesis

Nutrients, Journal Year: 2024, Volume and Issue: 16(14), P. 2222 - 2222

Published: July 11, 2024

This review summarizes the relationship between diet, gut microbiome, and migraine. Key findings reveal that certain dietary factors, such as caffeine alcohol, can trigger migraine, while nutrients like magnesium riboflavin may help alleviate migraine symptoms. The through its influence on neuroinflammation (e.g., vagus nerve cytokines), gut–brain signaling gamma-aminobutyric acid), metabolic function short-chain fatty acids), plays a crucial role in susceptibility. Migraine also alter eating behaviors, leading to poor nutritional choices further exacerbating condition. Individual variability diet microbiome composition highlights need for personalized prebiotic interventions. Epidemiological clinical data support effectiveness of tailored approaches, elimination diets inclusion beneficial nutrients, managing More work is needed confirm prebiotics, probiotics, potentially fecal translation management Future research should focus large-scale studies elucidate underlying mechanisms bidirectional interaction develop evidence-based guidelines. Integrating management, health optimization, lifestyle modifications offer holistic approach reducing frequency severity, ultimately improving patient outcomes quality life.

Language: Английский

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Microencapsulation with fructooligosaccharides and whey protein enhances the antioxidant activity of anthocyanins and their ability to modulate gut microbiota in vitro

Food Research International, Journal Year: 2024, Volume and Issue: 181, P. 114082 - 114082

Published: Feb. 9, 2024

Language: Английский

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Gut microbial metabolism in Alzheimer's disease and related dementias

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(6), P. e00470 - e00470

Published: Oct. 1, 2024

Multiple studies over the last decade have established that Alzheimer's disease and related dementias (ADRD) are associated with changes in gut microbiome. These alterations organismal composition result abundances of functions encoded by microbial community, including metabolic capabilities, which likely impact host mechanisms. Gut microbes access dietary components other molecules made produce metabolites can enter circulation cross blood-brain barrier (BBB). In recent years, several been or shown to influence pathways relevant ADRD pathology. include short chain fatty acids, secondary bile tryptophan derivatives (such as kynurenine, serotonin, tryptamine, indoles), trimethylamine/trimethylamine N-oxide. Notably, some these BBB various effects on brain, modulating release neurotransmitters neuronal function, inducing oxidative stress inflammation, impacting synaptic function. Microbial also central nervous system through immune, enteroendocrine, enteric pathways, perturbations turn function peripheral immune responses, well integrity, homeostasis neurogenesis, glial cell maturation activation. This review examines evidence supporting notion is influenced microbiota its metabolites. The potential therapeutic advantages for preventing treating discussed, highlighting their role developing new treatments.

Language: Английский

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Effect of a Vegan Diet on Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14924 - 14924

Published: Nov. 29, 2022

There is evidence indicating that a vegan diet could be beneficial in the prevention of neurodegenerative disorders, including Alzheimer's disease (AD). The purpose this review to summarize current knowledge on positive and negative aspects regarding risk AD. Regarding AD prevention, includes low levels saturated fats cholesterol, contributing healthy blood lipid profile. Furthermore, it rich phytonutrients, such as vitamins, antioxidants, dietary fiber, may help prevent cognitive decline. Moreover, contributes assumption quercetin, natural inhibitor monoamine oxidase (MAO), which can contribute maintaining mental health reducing risk. Nonetheless, data available do not allow an assessment whether strict veganism for compared with vegetarianism or other diets. A lacks specific vitamins micronutrients result nutritional deficiencies. Vegans supplementing are more prone vitamin B12, D, DHA deficiencies, have been linked Thus, evaluation net effect and/or progression should ascertained by taking into account all effects described here.

Language: Английский

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Dementia, infections and vaccines: 30 years of controversy

Aging Clinical and Experimental Research, Journal Year: 2023, Volume and Issue: 35(6), P. 1145 - 1160

Published: May 9, 2023

Abstract This paper reports the proceedings of a virtual meeting convened by European Interdisciplinary Council on Ageing (EICA), to discuss involvement infectious disorders in pathogenesis dementia and neurological leading dementia. We recap how our view etiology has changed over last 30 years light emerging evidence, we present evidence support implication infection dementia, notably Alzheimer’s disease (AD). The bacteria viruses thought be responsible for neuroinflammation damage are reviewed. then review genetic basis highlighting genes that currently focus investigation as potential targets therapy. Next, describe antimicrobial hypothesis intriguing possibility amyloid beta may itself possess properties. further clinical relevance gut–brain axis mechanisms which can move from intestine brain, recent findings regarding dysbiosis patterns patients with AD. specific pathogens disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex type 1 (HSV1), influenza. Finally, look at role vaccination prevent In conclusion, there is large body supporting various but large-scale studies long-term follow-up needed elucidate play, especially before subclinical or present.

Language: Английский

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