The Microbiota-Gut-Brain Axis

Physiological Reviews, Год журнала: 2019, Номер 99(4), С. 1877 - 2013

Опубликована: Авг. 28, 2019

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, past 15 yr have seen emergence microbiota (the trillions microorganisms within and on our bodies) as one key regulators function led to appreciation a distinct microbiota-gut-brain axis. This is gaining ever more traction fields investigating biological physiological basis psychiatric, neurodevelopmental, age-related, neurodegenerative disorders. brain communicate with each other via various routes including immune system, tryptophan metabolism, vagus nerve enteric nervous involving microbial metabolites such short-chain fatty acids, branched chain amino peptidoglycans. Many factors can influence composition early life, infection, mode birth delivery, use antibiotic medications, nature nutritional provision, environmental stressors, host genetics. At extreme diversity diminishes aging. Stress, particular, significantly impact at all stages life. Much recent work implicated gut many conditions autism, anxiety, obesity, schizophrenia, Parkinson’s disease, Alzheimer’s disease. Animal models paramount linking regulation fundamental neural processes, neurogenesis myelination, microbiome activation microglia. Moreover, translational human studies are ongoing will greatly enhance field. Future focus understanding mechanisms underlying attempt elucidate microbial-based intervention therapeutic strategies for neuropsychiatric

Язык: Английский

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The gut microbiome in neurological disorders

The Lancet Neurology, Год журнала: 2019, Номер 19(2), С. 179 - 194

Опубликована: Ноя. 18, 2019

Язык: Английский

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Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression

Cell Research, Год журнала: 2019, Номер 29(10), С. 787 - 803

Опубликована: Сен. 6, 2019

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet role of microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link neuroinflammation progression. Using mouse models, discovered that, during alteration composition leads to peripheral accumulation phenylalanine isoleucine, which stimulates differentiation proliferation pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated Th1 immune cells are associated with M1 microglia activation, contributing AD-associated neuroinflammation. Importantly, elevation isoleucine concentrations increase cell frequency blood were also observed two small independent cohorts patients mild cognitive impairment (MCI) due AD. Furthermore, GV-971, sodium oligomannate that demonstrated solid consistent cognition improvement phase 3 clinical trial China, suppresses phenylalanine/isoleucine accumulation, harnesses reverses impairment. Together, our findings highlight dysbiosis-promoted progression suggest novel strategy for therapy by remodelling microbiota.

Язык: Английский

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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2020, Номер 15(1)

Опубликована: Июль 16, 2020

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There currently no effective treatment for AD, which may be attributed part to lack of a clear underlying mechanism. Studies within last few decades provide growing evidence central role amyloid β (Aβ) and tau, as well glial contributions various molecular cellular pathways AD pathogenesis. Herein, we review recent progress with respect Aβ- tau-associated mechanisms, discuss dysfunction emphasis on neuronal receptors that mediate Aβ-induced toxicity. We also other critical factors affect pathogenesis, including genetics, aging, variables related environment, lifestyle habits, describe potential apolipoprotein E (APOE), viral bacterial infection, sleep, microbiota. Although have gained much towards understanding aspects this devastating disorder, greater commitment research mechanism, diagnostics will needed future research.

Язык: Английский

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Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders

Nutrients, Год журнала: 2021, Номер 13(6), С. 2099 - 2099

Опубликована: Июнь 19, 2021

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among metabolic, peripheral immune, central nervous systems via microbiota–gut–brain axis. However, it not well understood how microbiome neurons mutually interact or these interactions affect normal functioning cognition. We summarize mechanisms whereby regulate production, transportation, neurotransmitters. also discuss dysbiosis affects function, especially neurodegenerative diseases such as Alzheimer’s disease Parkinson’s disease.

Язык: Английский

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Update of the list of QPS‐recommended biological agents intentionally added to food or feed as notified to EFSA 13: suitability of taxonomic units notified to EFSA until September 2020

EFSA Journal, Год журнала: 2021, Номер 19(1)

Опубликована: Янв. 1, 2021

The qualified presumption of safety (QPS) approach was developed to provide a regularly updated generic pre-evaluation the biological agents, intended for addition food or feed, support work EFSA's Scientific Panels. It is based on an assessment published data each agent, with respect its taxonomic identity, body knowledge, concerns and antimicrobial resistance. Safety identified unit (TU) are, where possible, confirmed at strain product level, reflected by 'qualifications'. In period covered this statement, no new information found that would change status previously recommended QPS TUs. Of 36 microorganisms notified EFSA between April September 2020, 33 were excluded; seven filamentous fungi (including Aureobasidium pullulans recent insights), one Clostridium butyricum, Enterococcus faecium, three Escherichia coli, Streptomyces spp. 20 TUs had been evaluated. Three evaluated; Methylorubrum extorquens Mycobacterium aurum first time Bacillus circulans re-assessed because update requested in relation mandate. M. are not due lack knowledge use feed chain aurum, uncertainty concerning pathogenicity potential. B. qualifications 'production purposes only' 'absence cytotoxic activity'.

Язык: Английский

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Fecal microbiota transplantation alleviated Alzheimer’s disease-like pathogenesis in APP/PS1 transgenic mice

Translational Psychiatry, Год журнала: 2019, Номер 9(1)

Опубликована: Авг. 5, 2019

Abstract Alzheimer’s disease (AD) is the most common dementia in elderly. Treatment for AD still a difficult task clinic. associated with abnormal gut microbiota. However, little known about role of fecal microbiota transplantation (FMT) AD. Here, we evaluated efficacy FMT treatment We used an APPswe/PS1dE9 transgenic (Tg) mouse model. Cognitive deficits, brain deposits amyloid-β (Aβ) and phosphorylation tau, synaptic plasticity as well neuroinflammation were assessed. Gut its metabolites short-chain fatty acids (SCFAs) analyzed by 16S rRNA sequencing 1 H nuclear magnetic resonance (NMR). Our results showed that could improve cognitive deficits reduce deposition mice. These improvements accompanied decreased tau protein levels Aβ40 Aβ42. observed increases Tg mice, showing postsynaptic density 95 (PSD-95) synapsin I expression increased after FMT. also decrease COX-2 CD11b mice found reversed changes SCFAs. Thus, may be potential therapeutic strategy

Язык: Английский

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Mild cognitive impairment has similar alterations as Alzheimer's disease in gut microbiota

Alzheimer s & Dementia, Год журнала: 2019, Номер 15(10), С. 1357 - 1366

Опубликована: Авг. 18, 2019

Abstract Objective Gut microbiota changes before the onset of Alzheimer's disease (AD) and alterations could be detected in stage mild cognitive impairment (MCI). The findings might offer diagnostic biomarkers dementia. Background AD is most common cause dementia, MCI predementia state. Recent studies suggest gut microbial communities associated with AD, whereas dementia has not been discovered characterized humans. New/Updated Hypothesis We hypothesize that dysbiosis happens stage. Patients have decreased diversity, for early detection AD. In our preliminary study, we identified differences between normal controls 11 genera from feces blood. No difference was detected. Using model fecal samples all different input, 93% (28 30) patients correctly. Major Challenges diagnosis study based on symptoms neuroimaging, should included precise further validating studies. Besides, as longitudinally, their relationship progress needs to studied prospective Linkage Other Theories Escherichia observed increased at genus level both blood MCI. For biomarker, postmortem brain tissue showed lipopolysaccharides gram‐negative coli fragments colocalize amyloid plaque. this way, pathogenesis would triggered during by shifting. systemic inflammatory reactions caused compounds secreted bacteria may impair blood‐brain barrier promote neuroinflammation and/or neurodegeneration. Furthermore, abnormal metabolites gene functions an impact

Язык: Английский

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Microbiota-Gut-Brain Axis: New Therapeutic Opportunities

The Annual Review of Pharmacology and Toxicology, Год журнала: 2019, Номер 60(1), С. 477 - 502

Опубликована: Сен. 11, 2019

The traditional fields of pharmacology and toxicology are beginning to consider the substantial impact our gut microbiota has on host physiology. microbiota-gut-brain axis is emerging as a particular area interest potential new therapeutic target for effective treatment central nervous system disorders, in addition being cause drug side effects. Microbiota-gut-brain signaling can occur via several pathways, including immune system, recruitment neurochemical signaling, direct enteric routes vagus nerve, production bacterial metabolites. Altered microbial profiles have been described psychiatric neurological disorders. Psychobiotics, live biotherapeutics or substances whose beneficial effects brain bacterially mediated, currently investigated and/or adjunctive therapies neurodevelopmental disorders possibly neurodegenerative disease, they may emerge options clinical management

Язык: Английский

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

Molecular Neurobiology, Год журнала: 2020, Номер 57(12), С. 5026 - 5043

Опубликована: Авг. 22, 2020

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

Язык: Английский

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