Microbiota-Brain-Gut Axis and Neurodegenerative Diseases

Current Neurology and Neuroscience Reports, Год журнала: 2017, Номер 17(12)

Опубликована: Окт. 17, 2017

Язык: Английский

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Brain-Gut-Microbiota Axis in Alzheimer’s Disease

Journal of Neurogastroenterology and Motility, Год журнала: 2019, Номер 25(1), С. 48 - 60

Опубликована: Янв. 10, 2019

Disturbances along the brain-gut-microbiota axis may significantly contribute to pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD) is most frequent cause dementia characterized by a progressive decline in cognitive function associated with formation amyloid beta (Aβ) plaques and neurofibrillary tangles. Alterations gut microbiota composition induce increased permeability barrier immune activation leading systemic inflammation, which turn impair blood-brain promote neuroinflammation, neural injury, ultimately neurodegeneration. Recently, Aβ has also been recognized as an antimicrobial peptide participating innate response. However, dysregulated state, reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry elicit cross-seeding misfolding microglial priming. The seeding propagation occur at different levels axis. potential mechanisms spreading include neuron-to-neuron or distal neuron spreading, direct crossing via other cells astrocytes, fibroblasts, microglia, system cells. A growing body experimental clinical data confirms key role dysbiosis microbiota-host interactions convergence gut-derived inflammatory response together aging poor diet elderly AD. Modification food-based therapy probiotic supplementation create new preventive therapeutic options

Язык: Английский

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Alzheimer’s disease hypothesis and related therapies

Translational Neurodegeneration, Год журнала: 2018, Номер 7(1)

Опубликована: Янв. 24, 2018

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause for dementia. There are many hypotheses about AD, including abnormal deposit of amyloid β (Aβ) protein in extracellular spaces neurons, formation twisted fibers tau proteins inside cholinergic neuron damage, inflammation, oxidative stress, etc., anti-AD drugs based on these have been developed. In this review, we will discuss existing emerging hypothesis related therapies.

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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Altered bile acid profile associates with cognitive impairment in Alzheimer's disease—An emerging role for gut microbiome

Alzheimer s & Dementia, Год журнала: 2018, Номер 15(1), С. 76 - 92

Опубликована: Окт. 15, 2018

Abstract Introduction Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and specific gut‐brain axis neurodegeneration. Bile acids (BAs), products of cholesterol metabolism clearance, are produced liver further metabolized by bacteria. They have major regulatory signaling functions seem dysregulated Alzheimer's disease (AD). Methods Serum levels 15 primary secondary BAs their conjugated forms were measured 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 late 305 AD cases enrolled Neuroimaging Initiative. We assessed associations BA profiles selected ratios diagnosis, cognition, AD‐related genetic variants, adjusting confounders multiple testing. Results In compared to we observed significantly lower serum concentrations (cholic acid [CA]) increased bacterially produced, BA, deoxycholic acid, its glycine taurine forms. An ratio acid:CA, which reflects 7α‐dehydroxylation CA bacteria, strongly associated decline, finding replicated brain samples Rush Religious Orders Memory Aging Project. Several variants immune response–related genes implicated showed profiles. Discussion report first time an association between altered profile, AD, changes using large multicenter study. These findings warrant investigation dysbiosis possible gut‐liver‐brain pathogenesis AD.

Язык: Английский

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Altered microbiomes distinguish Alzheimer’s disease from amnestic mild cognitive impairment and health in a Chinese cohort

Brain Behavior and Immunity, Год журнала: 2019, Номер 80, С. 633 - 643

Опубликована: Май 8, 2019

(Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of main causes disability in elder people worldwide. Recently, several animal studies indicated that 'gut-brain' axis might contribute to amyloid deposition AD. However, data about gut dysbiosis human AD remains scarce literature, especially including whole process In this prospective cross-sectional study, we aimed at identifying differences microbiome between patients with (Pre-onset stage amnestic mild aMCI; AD) normal cognition healthy controls (HC). Additionally, potential association IM clinical characteristics was evaluated. A total 97 subjects (33 AD, 32 aMCI, HC) were recruited study. The composition bacterial communities determined 16S ribosomal RNA Miseq sequencing. addition, Phylogenetic Investigation Communities Reconstruction Unobserved States (PICRUSt) used predict function shift intestinal microbiota. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores evaluate severity impairment patients. fecal microbial diversity decreased compared aMCI HC. And distinct among control groups. Among taxa, proportion phylum Firmicutes significantly reduced (P = 0.008), whereas Proteobacteria 0.024) highly enriched similar alterations observed order, class family levels these two phyla. Gammaproteobacteria, Enterobacteriales Enterobacteriaceae showed a prevalence from HC Further, significant correlation abundance altered microbiomes. Moreover, KEGG results increased modules related glycan biosynthesis metabolism pathways immune system Importantly, discriminating models based on predominant microbiota could effectively distinguish (AUC 0.890, 0.940, respectively), also 0.925). Notably, both 0.688) 0.698). Distinct communities, Enterobacteriaceae, associated when predementia subjects. These novel findings will give new clues understand provide therapeutic target for intervention marker disease.

Язык: Английский

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Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment

EBioMedicine, Год журнала: 2019, Номер 47, С. 529 - 542

Опубликована: Авг. 30, 2019

Alzheimer's disease (AD) prevalence is increasing, but its etiology remains elusive. Gut microbes can contribute to AD pathology and may help identifying novel markers therapies against AD. Herein, we examine how the gut microbiome differs in older adults with mild cognitive impairment compared cognitively normal counterparts, whether a modified Mediterranean-ketogenic diet (MMKD) alters signature association cerebrospinal fluid (CSF) biomarkers.A randomized, double-blind, cross-over, single-center pilot study of MMKD versus American Heart Association Diet (AHAD) intervention performed on 17 subjects (age: 64.6 ± 6.4 yr), which 11 have impairment, while 6 are normal. Subjects undergo AHAD for 6-weeks separated by washout periods. microbiome, fecal short-chain fatty acids (SCFAs), CSF including amyloid β (Aβ)-40 Aß-42, total tau, phosphorylated tau-181 (tau-p181) measured at before after interventions.At baseline, vs. impaired cognition show no notable difference diversity several unique microbial signatures detected impairment. Proteobacteria correlate positively Aβ-42: Aβ-40 propionate butyrate correlates negatively Aβ-42 Several bacteria differently affected two diets distinct patterns between subjects. Notably, abundance Enterobacteriaceae, Akkermansia, Slackia, Christensenellaceae Erysipelotriaceae increases that Bifidobacterium Lachnobacterium reduces MMKD, Mollicutes. slightly lactate acetate increasing butyrate. Conversely, reducing butyrate.The data suggest specific depict modulate metabolites improved biomarkers CSF.

Язык: Английский

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Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease

Journal of Neuroinflammation, Год журнала: 2018, Номер 15(1)

Опубликована: Сен. 24, 2018

Alzheimer’s disease (AD) is a neurodegenerative disorder, most cases of which lack clear causative event. This has made the difficult to characterize and, thus, diagnose. Although some are genetically linked, there many diseases and lifestyle factors that can lead an increased risk developing AD, including traumatic brain injury, diabetes, hypertension, obesity, other metabolic syndromes, in addition aging. Identifying common trends between these conditions could enhance our understanding AD development more effective treatments. immune system one body’s key defense mechanisms, chronic inflammation been increasingly linked with several age-related diseases. Moreover, it now well accepted important role onset progression AD. In this review, different inflammatory signals associated its will be outlined demonstrate how may influencing individual susceptibility Our goal bring attention potential shared presented by during successful

Язык: Английский

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Microbiome–host systems interactions: protective effects of propionate upon the blood–brain barrier

Microbiome, Год журнала: 2018, Номер 6(1)

Опубликована: Март 21, 2018

Gut microbiota composition and function are symbiotically linked with host health altered in metabolic, inflammatory neurodegenerative disorders. Three recognised mechanisms exist by which the microbiome influences gut-brain axis: modification of autonomic/sensorimotor connections, immune activation, neuroendocrine pathway regulation. We hypothesised interactions between circulating gut-derived microbial metabolites, blood-brain barrier (BBB) also contribute to axis. Propionate, produced from dietary substrates colonic bacteria, stimulates intestinal gluconeogenesis is associated reduced stress behaviours, but its potential endocrine role has not been addressed.After demonstrating expression propionate receptor FFAR3 on human brain endothelium, we examined impact a physiologically relevant concentration (1 μM) BBB properties vitro. Propionate inhibited pathways non-specific infections via CD14-dependent mechanism, suppressed LRP-1 protected oxidative NRF2 (NFE2L2) signalling.Together, these results suggest metabolites interact BBB, representing fourth facet axis that warrants further attention.

Язык: Английский

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The Gut–Brain Axis and the Microbiome: Mechanisms and Clinical Implications

Clinical Gastroenterology and Hepatology, Год журнала: 2018, Номер 17(2), С. 322 - 332

Опубликована: Окт. 4, 2018

Язык: Английский

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