A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Feb. 11, 2020

Amyloids are a class of protein with unique self-aggregation properties, and their aberrant accumulation can lead to cellular dysfunctions associated neurodegenerative diseases. While genetic environmental factors influence amyloid formation, molecular triggers and/or facilitators not well defined. Growing evidence suggests that non-identical proteins may accelerate reciprocal aggregation in prion-like fashion. humans encode ~30 amyloidogenic proteins, the gut microbiome also produces functional amyloids. For example, curli cell surface abundantly expressed by certain bacteria. In mice overexpressing human α-synuclein (αSyn), we reveal colonization curli-producing Escherichia coli promotes αSyn pathology brain. Curli expression is required for E. exacerbate αSyn-induced behavioral deficits, including intestinal motor impairments. Purified subunits biochemical assays, while oral treatment gut-restricted inhibitor prevents curli-mediated acceleration abnormalities. We propose exposure microbial amyloids gastrointestinal tract disease

Language: Английский

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Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential

Translational Neurodegeneration, Journal Year: 2022, Volume and Issue: 11(1)

Published: Jan. 28, 2022

Abstract Synaptic abnormalities are a cardinal feature of Alzheimer’s disease (AD) that known to arise as the progresses. A growing body evidence suggests pathological alterations neuronal circuits and synapses may provide mechanistic link between amyloid β (Aβ) tau pathology thus serve an obligatory relay cognitive impairment in AD. Brain-derived neurotrophic factors (BDNFs) play important role maintaining synaptic plasticity learning memory. Considering AD disorder, BDNF has attracted increasing attention potential diagnostic biomarker therapeutical molecule for Although depletion been linked with Aβ accumulation, phosphorylation, neuroinflammation apoptosis, exact mechanisms underlying effect impaired signaling on still unknown. Here, we present overview how genomic structure is connected regulate signaling. We then discuss BDNF-targeting therapeutics

Language: Английский

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Fecal Microbiota Transplantation in Neurological Disorders

Frontiers in Cellular and Infection Microbiology, Journal Year: 2020, Volume and Issue: 10

Published: March 24, 2020

Background Several studies suggested an important role of the gut microbiota in pathophysiology neurological disorders, implying that alteration might serve as a treatment strategy. Fecal transplantation (FMT) is currently most effective intervention and accepted for recurrent Clostridioioides difficile infections. To evaluate indications FMT patients with we summarized available literature on FMT. In addition, provide suggestions future directions. Methods July 2019, five main databases were searched case descriptions disorders humans or animal models. ClinicalTrials.gov website was consulted registered planned ongoing trials. Results Of 541 identified studies, 34 included analysis. Clinical trials have been performed autism spectrum disorder showed beneficial effects symptoms. For multiple sclerosis Parkinson's disease, several positive effect FMT, supported by some reports humans. epilepsy, Tourette syndrome, diabetic neuropathy but evidence restricted to limited numbers studies. stroke, Alzheimer's disease Guillain-Barré syndrome only models identified. These potential healthy donor contrast, one study model stroke increased mortality after Whether findings from can be confirmed human diseases awaits seen. above mentioned are ongoing, well amyotrophic lateral sclerosis. Conclusions Preliminary suggests may promising option disorders. However, still scanty contrasting results observed. Limited while experiments conducted. Large double-blinded randomized controlled needed further elucidate

Language: Английский

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A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders

Clinical Microbiology Reviews, Journal Year: 2022, Volume and Issue: 35(1)

Published: Jan. 5, 2022

The human body is full of an extensive number commensal microbes, consisting bacteria, viruses, and fungi, collectively termed the microbiome. initial acquisition microbiota occurs from both external maternal environments, vast majority them colonize gastrointestinal tract (GIT). These microbial communities play a central role in maturation development immune system, nervous GIT system are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect composition gut microbiota. Recent publications have highlighted that imbalance microflora, known as dysbiosis, associated with onset progression neurological disorders. Moreover, characterization microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical clinical research on interventions related to microbiome treating conditions, autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's epilepsy, stroke, hold significant promise. This review aims present comprehensive overview potential involvement pathogenesis particular emphasis microbe-based therapies and/or diagnostic biomarkers. discusses health benefits administration probiotics, prebiotics, postbiotics, synbiotics fecal transplantation

Language: Английский

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

Molecular and Cellular Endocrinology, Journal Year: 2022, Volume and Issue: 546, P. 111572 - 111572

Published: Jan. 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.

Language: Английский

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Clinical Application and Potential of Fecal Microbiota Transplantation

Annual Review of Medicine, Journal Year: 2018, Volume and Issue: 70(1), P. 335 - 351

Published: Nov. 7, 2018

Fecal microbiota transplantation (FMT) is a well-established treatment for recurrent Clostridioides difficile infection. FMT has become more readily available and useful new option as result of stool banks. The current state knowledge indicates that dysbiosis the gut implicated in several disorders addition to C. Randomized controlled studies have shown be somewhat effective treating ulcerative colitis, irritable bowel syndrome, hepatic encephalopathy. In addition, been beneficial other conditions, such eradication multidrug-resistant organisms graft-versus-host disease. We expect will soon implemented strategy indications, although further are needed.

Language: Английский

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

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Microglia, Lifestyle Stress, and Neurodegeneration

Immunity, Journal Year: 2020, Volume and Issue: 52(2), P. 222 - 240

Published: Jan. 7, 2020

Language: Английский

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Gut–Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(20), P. 7551 - 7551

Published: Oct. 13, 2020

The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has largest and vulnerable surface with desirable features to observe foods, nutrients, environmental factors, well differentiate commensals, invading pathogens, others. It is well-known a strong connection central nervous system (CNS) in context health disease. A healthy diverse microbes vital for normal brain functions emotional behaviors. In addition, CNS controls most aspects GI physiology. molecular interaction between gut/microbiome complex bidirectional, ensuring maintenance homeostasis proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, metabolites-dependent pathways. Changes bidirectional relationship GIT are linked pathogenesis neurological disorders; therefore, microbiota/gut-and-brain axis emerging widely accepted concept. this review, we summarize recent findings supporting role microbiota immune on development disorders. highlight advances improving diseases by probiotics/prebiotics/synbiotics fecal transplantation via concept gut–brain axis.

Language: Английский

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Dietary fructose-induced gut dysbiosis promotes mouse hippocampal neuroinflammation: a benefit of short-chain fatty acids

Microbiome, Journal Year: 2019, Volume and Issue: 7(1)

Published: June 29, 2019

Western-style diets arouse neuroinflammation and impair emotional cognitive behavior in humans animals. Our previous study showed that a high-fructose diet caused the hippocampal neuroinflammatory response neuronal loss animals, but underlying mechanisms remained elusive. Here, alterations gut microbiota intestinal epithelial barrier were investigated as causes of induced by diet.A response, reactive gliosis, C57BL/6N mice. Depletion using broad-spectrum antibiotics suppressed fructose-fed mice, these animals still exhibited loss. Gut compositional alteration, short-chain fatty acids (SCFAs) reduction, impairment, NOD-like receptor family pyrin domain-containing 6 (NLRP6) inflammasome dysfunction, high levels serum endotoxin, FITC-dextran observed Of note, SCFAs, well pioglitazone (a selective peroxisome proliferator-activated gamma (PPAR-γ) agonist), shaped ameliorated impairment NLRP6 dysfunction Moreover, SCFAs-mediated activation was inhibited histamine bacterial metabolite) ex vivo colonic explants murine CT26 colon carcinoma cells transfected with siRNA. However, GW9662 PPAR-γ antagonist) exerted no impact on explants, suggesting SCFAs may stimulate independently activation. prevented fructose-induced Additionally, activated increased DCX+ newborn neurons DG control mice.Our findings reveal dysbiosis is critical factor for diet-induced mice possibly mediated impairing barrier. Mechanistically, defective responsible impairment. can ameliorate barrier, resulting protection against This addresses gap understanding injury associated diets. A new intervention strategy reducing risk neurodegenerative diseases through supplementation or dietary fiber consumption emphasized.

Language: Английский

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