Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Март 5, 2022

The implication of gut microbiota in the control brain functions health and disease is a novel, currently emerging concept. Accumulating data suggest that exert its action at least part by modulating neuroinflammation. Given link between neuroinflammatory changes neuronal activity, it plausible may affect indirectly impacting microglia, key player Indeed, increasing evidence suggests interplay microglia synaptic dysfunction involve microbiota, among other factors. In addition to these indirect microglia-dependent actions on has been recently recognized could also activity directly stimulation vagus nerve.

Язык: Английский

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The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment

Nutrients, Год журнала: 2022, Номер 14(3), С. 668 - 668

Опубликована: Фев. 5, 2022

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation implicated in the pathogenesis several gastrointestinal extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through increasingly defined brain axis, opening possibility for new microbiota-based therapeutic options. Although studies conducted unravel possible relationship between Alzheimer’s Disease (AD) progression, diagnostic potential approaches aiming at restoring eubiosis remain be fully addressed. In this narrative review, we briefly summarize role homeostasis health disease, present evidence AD patients. Based on these observations, then discuss how dysbiosis might exploited tool early advanced stages, examine prebiotics, probiotics, fecal transplantation, diets complementary interventions thus offering insights into diagnosis treatment devastating progressive disease.

Язык: Английский

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Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis

Brain, Год журнала: 2023, Номер 146(12), С. 4916 - 4934

Опубликована: Окт. 18, 2023

Alzheimer's disease is a complex neurodegenerative disorder leading to decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor by showing specific alterations microbiome composition of patients rodent models. However, it unknown whether are causal manifestation symptoms. To understand involvement patient host physiology behaviour, we transplanted faecal from age-matched healthy controls into microbiota-depleted young adult rats. We found impairments behaviours reliant on hippocampal neurogenesis, essential process for certain memory functions mood, resulting transplants. Notably, severity correlated with clinical scores donor patients. Discrete changes rat caecal metabolome were also evident. As neurogenesis cannot be measured living humans but modulated circulatory systemic environment, assessed impact environment proxy readouts. Serum decreased human cells vitro associated key microbial genera. Our findings reveal first time, that symptoms can transferred organism via microbiota, confirming role disease, highlight converging central cellular regulating gut-mediated factors Alzheimer's.

Язык: Английский

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Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

Frontiers in Aging Neuroscience, Год журнала: 2021, Номер 13

Опубликована: Май 28, 2021

Alzheimer's disease (AD) is the most common age-related progressive neurodegenerative disease, characterized by a decline in cognitive function and neuronal loss, caused several factors. Numerous clinical experimental studies have suggested involvement of gut microbiota dysbiosis patients with AD. The altered can influence brain behavior through microbiota-gut-brain axis via various pathways such as increased amyloid-β deposits tau phosphorylation, neuroinflammation, metabolic dysfunctions, chronic oxidative stress. With no current effective therapy to cure AD, modulation may be promising therapeutic option prevent or delay onset AD counteract its progression. Our present review summarizes alterations pathogenetic roles mechanisms microbiota-targeted therapies for Understanding between will help decipher pathogenesis from novel perspectives shed light on strategies

Язык: Английский

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Microbiota-derived metabolite Indoles induced aryl hydrocarbon receptor activation and inhibited neuroinflammation in APP/PS1 mice

Brain Behavior and Immunity, Год журнала: 2022, Номер 106, С. 76 - 88

Опубликована: Авг. 10, 2022

Gut microbiota alterations might affect the development of Alzheimer's disease (AD) through microbiota-derived metabolites. For example, Indoles via tryptophan metabolism prevented Aβ accumulation and Tau hyperphosphorylation, restored synaptic plasticity, then promoted cognitive behavioral ability APP/PS1 mice. The imbalanced compositions Indoles-producing bacteria with deficiency were found in male mice, but molecular mechanisms remained unclear. Our current study revealed that (including indole, indole-3-acetic acid indole-3-propionic acid) upregulated production aryl hydrocarbon receptor (AhR), inhibited activation NF-κB signal pathway as well formation NLRP3 inflammasome, reduced release inflammatory cytokines, including TNF-α, IL-6, IL-1β IL-18, alleviating response These findings demonstrated roles activating AhR to regulate neuroinflammation AD gut Indoles, which implied a novel way for treatment.

Язык: Английский

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Gut microbiome, cognitive function and brain structure: a multi-omics integration analysis

Translational Neurodegeneration, Год журнала: 2022, Номер 11(1)

Опубликована: Ноя. 14, 2022

Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. This study was aimed to investigate associations gut microbiome with based on multi-omics three independent populations.

Язык: Английский

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Periodontal microorganisms and Alzheimer disease – A causative relationship?

Periodontology 2000, Год журнала: 2022, Номер 89(1), С. 59 - 82

Опубликована: Март 4, 2022

Abstract In the initiation or exacerbation of Alzheimer disease, dissemination oral microorganisms into brain tissue low‐level systemic inflammation have been speculated to play a role. However, impact microorganisms, such as Porphyromonas gingivalis , on pathogenesis disease and potential causative relationship is still unclear. The present review has critically reviewed literature by examining following aspects: (a) microbiome immune response in elderly population, (b) human studies association between periodontal gut (c) animal vitro (d) preventive therapeutic approaches. Factors contributing microbial dysbiosis seem be aging, local inflammation, diseases, wearing dentures, living nursing homes no access adequate hygiene measures. was detectable post‐mortem samples. Microbiome analyses saliva samples biofilms showed decreased diversity different composition compared cognitively healthy subjects. Many in‐vitro underline P induce disease‐related alterations. models, recurring applications its components increased pro‐inflammatory mediators β‐amyloid deteriorated animals' cognitive performance. Since periodontitis result disturbed homoeostasis, an effect therapy host related parameters may suggested should elucidated further clinical trials.

Язык: Английский

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Genetic correlations between Alzheimer’s disease and gut microbiome genera

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Март 31, 2023

Abstract A growing body of evidence suggests that dysbiosis the human gut microbiota is associated with neurodegenerative diseases like Alzheimer’s disease (AD) via neuroinflammatory processes across microbiota-gut-brain axis. The affects brain health through secretion toxins and short-chain fatty acids, which modulates permeability numerous immune functions. Observational studies indicate AD patients have reduced microbiome diversity, could contribute to pathogenesis disease. Uncovering genetic basis microbial abundance its effect on suggest lifestyle changes may reduce an individual’s risk for Using largest genome-wide association study genera from MiBioGen consortium, we used polygenic score (PRS) analyses “best-fit” model implemented in PRSice-2 determined correlation between 119 a discovery sample (ADc12 case/control: 1278/1293). To confirm results sample, next repeated PRS analysis replication (GenADA 799/778) then performed meta-analysis both samples. Finally, conducted linear regression assess PRSs significant APOE genotypes. In 20 were initially identified as genetically case/control status. Of these 20, three ( Eubacterium fissicatena protective factor , Collinsella, Veillonella factor) independently sample. Meta-analysis samples confirmed ten had AD, four significantly rs429358 allele direction consistent their protective/risk designation association. Notably, proinflammatory genus was positively correlated Overall, host factors influencing are suggesting serve biomarkers targets treatment intervention. Our highlight might promote development interaction . Larger datasets functional required understand causal relationships.

Язык: Английский

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Effect of Probiotic Bifidobacterium breve in Improving Cognitive Function and Preventing Brain Atrophy in Older Patients with Suspected Mild Cognitive Impairment: Results of a 24-Week Randomized, Double-Blind, Placebo-Controlled Trial

Journal of Alzheimer s Disease, Год журнала: 2022, Номер 88(1), С. 75 - 95

Опубликована: Май 10, 2022

Background: Probiotics have been reported to ameliorate cognitive impairment. Objective: We investigated the effect of probiotic strain Bifidobacterium breve MCC1274 (A1) in enhancing cognition and preventing brain atrophy older patients with mild impairment (MCI). Methods: In this RCT, 130 aged from 65 88 years old suspected MCI received once daily either (B. MCC1274, 2×1010 CFU) or placebo for 24 weeks. Cognitive functions were assessed by ADAS-Jcog MMSE tests. Participants underwent MRI determine changes using Voxel-based Specific Regional Analysis System Alzheimer’s disease (VSRAD). Fecal samples collected analysis gut microbiota composition. Results: was performed on 115 participants as full set (probiotic 55, 60). subscale “orientation” significantly improved compared at subscales “orientation time” “writing” lower baseline (< 25) subgroup VSRAD scores worsened group; supplementation tended suppress progression, particular among those subjects progressed (VOI Z-score ≥1.0). There no marked overall composition supplementation. Conclusion: Improvement function observed some only likely due sensitiveness these tests subjects. consumption weeks suppressed suggesting that B. helps prevent

Язык: Английский

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The gut microbiome, mild cognitive impairment, and probiotics: A randomized clinical trial in middle-aged and older adults

Clinical Nutrition, Год журнала: 2022, Номер 41(11), С. 2565 - 2576

Опубликована: Сен. 28, 2022

Язык: Английский

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