The gut microbiome as a modulator of healthy ageing

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2022, Номер 19(9), С. 565 - 584

Опубликована: Апрель 25, 2022

Язык: Английский

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Short chain fatty acids: Microbial metabolites for gut-brain axis signalling

Molecular and Cellular Endocrinology, Год журнала: 2022, Номер 546, С. 111572 - 111572

Опубликована: Янв. 20, 2022

The role of the intestinal microbiota as a regulator gut-brain axis signalling has risen to prominence in recent years. Understanding relationship between gut microbiota, metabolites it produces, and brain will be critical for subsequent development new therapeutic approaches, including identification novel psychobiotics. A key focus this regard have been short-chain fatty acids (SCFAs) produced by bacterial fermentation dietary fibre, which include butyrate, acetate, propionate. Ongoing research is focused on entry SCFAs into systemic circulation from lumen, their migration cerebral across blood barrier, potential exert acute chronic effects structure function. This review aims discuss our current mechanistic understanding direct indirect influence that function, behaviour physiology, inform future microbiota-targeted interventions disorders.

Язык: Английский

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Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition

eLife, Год журнала: 2021, Номер 10

Опубликована: Апрель 13, 2021

Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, mechanisms microbiome–brain interaction AD were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as microbial metabolites which promote Aβ deposition. Germ-free (GF) mice exhibit substantially reduced plaque load and markedly SCFA plasma concentrations; conversely, supplementation to GF increased levels conventionally colonized (specific pathogen-free [SPF]) animals SPF even further exacerbated load. This was accompanied by pronounced alterations microglial transcriptomic profile, including upregulation ApoE. Despite recruitment plaques upon supplementation, microglia contained less intracellular Aβ. Taken together, our results demonstrate that are critical mediators along gut-brain axis deposition likely via modulation phenotype.

Язык: Английский

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Microbiota-derived metabolites as drivers of gut–brain communication

Gut Microbes, Год журнала: 2022, Номер 14(1)

Опубликована: Июль 28, 2022

Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The microbes transform metabolize dietary- host-derived molecules generating diverse group metabolites local systemic effects. bi-directional communication between brain residing gut, so-called gut–brain axis, consists network immunological, neuronal, endocrine signaling pathways. Although full variety mechanisms crosstalk is yet to be established, existing data demonstrates that single metabolite or its derivatives are likely among key inductors within axis communication. However, more research needed understand molecular underlying how alter functions, examine if different interventional approaches targeting could used prevention treatment neurological disorders, as reviewed herein.Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood–brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic ZO Zonula occludens proteins

Язык: Английский

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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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Challenges and hopes for Alzheimer’s disease

Drug Discovery Today, Год журнала: 2022, Номер 27(4), С. 1027 - 1043

Опубликована: Фев. 1, 2022

Язык: Английский

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Interplay of gut microbiota and oxidative stress: Perspective on neurodegeneration and neuroprotection

Journal of Advanced Research, Год журнала: 2021, Номер 38, С. 223 - 244

Опубликована: Сен. 17, 2021

Recent research on the implications of gut microbiota brain functions has helped to gather important information relationship between them. Pathogenesis neurological disorders is found be associated with dysregulation gut-brain axis. Some bacteria metabolites are directly increase in reactive oxygen species levels, one most risk factors neurodegeneration. Besides their morbid association, also play a significant role reducing onset these life-threatening disorders.Studies done recent past raises two link and brain: "gut microbiota-oxidative stress-neurodegeneration" microbiota-antioxidant-neuroprotection. This review aims gives deep insight our readers, collective studies done, focusing mediated oxidative stress involved neurodegeneration along focus those showing involvement neuroprotection.This focused three main key concepts. Firstly, mounting evidences from clinical preclinical arenas shows influence resulting dysfunctional processes. Therefore, we describe potential influencing vulnerability stress, budding causative Alzheimer's Parkinson's disease. Secondly, contributing roles been observed attenuating inflammation via its own or by producing secondary and, modulation population antioxidative anti-inflammatory probiotics have shown promising neuro resilience. Thirdly, high throughput silico tools databases correlation microbiome, health, thus providing fascinating perspective new avenues for therapeutic options.

Язык: Английский

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Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease

Neurology, Год журнала: 2022, Номер 98(8)

Опубликована: Янв. 7, 2022

Background and Objectives

Short-chain fatty acids (SCFAs) are gut microbial metabolites that promote the disease process in a rodent model of Parkinson (PD), but fecal levels SCFAs patients with PD reduced. Simultaneous assessments plasma SCFA levels, their interrelationships process, scarce. We aimed to compare different subtypes healthy controls delineate interrelations link microbiota changes clinical severity PD.

Methods

A cohort 96 85 were recruited from National Taiwan University Hospital. Fecal concentrations measured using chromatography mass spectrometry. Gut was analyzed metagenomic shotgun sequencing. Body index medical comorbidities evaluated dietary information obtained food frequency questionnaire. To assess motor cognitive impairment, we used Movement Disorder Society–Unified Parkinson9s Disease Rating Scale (MDS-UPDRS) Mini-Mental Status Examination (MMSE).

Results

Compared controls, had lower higher acetate, propionate, butyrate. After adjustment for age, sex, duration, anti-PD medication dosage, MDS-UPDRS part III scores correlated reduced acetate (ρ = −0.37, p 0.012), propionate −0.32, 0.036), butyrate −0.40, 0.004) increased 0.26, 0.042) MMSE negatively −0.09, 0.027) valerate −0.032, 0.033) after confounders. SCFAs-producing bacteria positively revealed no association In patient group, abundance proinflammatory microbes, such as Clostridiales bacterium NK3B98 Ruminococcus sp AM07-15, significantly decreased SCFAs, especially propionic acid.

Discussion

Reductions observed corelated specific

Classification Evidence

This study provides Class evidence metabolite distinguish between associated

Язык: Английский

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Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease

Science Translational Medicine, Год журнала: 2023, Номер 15(700)

Опубликована: Июнь 14, 2023

Alzheimer’s disease (AD) pathology is thought to progress from normal cognition through preclinical and ultimately symptomatic AD with cognitive impairment. Recent work suggests that the gut microbiome of patients has an altered taxonomic composition compared healthy, cognitively control individuals. However, knowledge about changes in before onset limited. In this cross-sectional study accounted for clinical covariates dietary intake, we microbial function a cohort 164 individuals, 49 whom showed biomarker evidence early AD. Gut profiles individuals were distinct those without The change correlated β-amyloid (Aβ) tau pathological biomarkers but not neurodegeneration, suggesting may process. We identified specific bacterial taxa associated Inclusion these features improved accuracy, sensitivity, specificity machine learning classifiers predicting status when tested on subset (65 participants). correlates neuropathology improve our understanding etiology help identify gut-derived markers risk.

Язык: Английский

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Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia

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

Опубликована: Июнь 17, 2022

A consequence of our progressively ageing global population is the increasing prevalence worldwide age-related cognitive decline and dementia. In absence effective therapeutic interventions, identifying risk factors associated with becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional communication system between gut, its microbiome, central nervous system, commonly referred to as microbiota-gut-brain axis, may be contributing factor for health disease. However, exact mechanisms remain undefined. Microbial-derived metabolites produced in gut can cross intestinal epithelial barrier, enter systemic circulation trigger physiological responses both directly indirectly affecting functions. Dysregulation this (i.e., dysbiosis) modulate cytotoxic metabolite production, promote neuroinflammation negatively impact cognition. review, we explore critical connections microbial-derived (secondary bile acids, trimethylamine-N-oxide (TMAO), tryptophan derivatives others) their influence upon function neurodegenerative disorders, particular interest less-explored role decline.

Язык: Английский

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