Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis

Microbiome, Journal Year: 2021, Volume and Issue: 9(1)

Published: Nov. 17, 2021

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between and brain in PD pathogenesis, known as microbiota-gut-brain axis. As an approach to re-establishing normal community, fecal transplantation (FMT) exerted beneficial effects on recent studies. Here, this study, we established chronic rotenone-induced mouse model evaluate protective of FMT treatment explore underlying mechanisms, which proves involvement dysbiosis pathogenesis via axis.We demonstrated induced by rotenone administration caused function impairment poor behavioral performances mice. Moreover, 16S RNA sequencing identified increase bacterial genera Akkermansia Desulfovibrio samples By contrast, remarkably restored microbial thus ameliorating dysfunctions Further experiments revealed alleviated intestinal inflammation barrier destruction, reducing levels systemic inflammation. Subsequently, attenuated blood-brain (BBB) suppressed neuroinflammation substantia nigra (SN), further decreased damage dopaminergic neurons. Additional mechanistic investigation discovered reduced lipopolysaccharide (LPS) colon, serum, SN, thereafter suppressing TLR4/MyD88/NF-κB signaling pathway its downstream pro-inflammatory products both SN colon.Our current study demonstrates can correct ameliorate model, suppression mediated LPS-TLR4 possibly plays significant role. Further, prove involved genesis Video abstract.

Language: Английский

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Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 7, 2022

It has been noticed in recent years that the unfavorable effects of gut microbiota could exhaust host vigor and life, yet knowledge theory are just beginning to be established. Increasing documentation suggests microbiota–gut–brain axis not only impacts brain cognition psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS). How blood–brain barrier (BBB), a machinery protecting central nervous system (CNS) from systemic circulation, allows risky factors derived translocated into seems paradoxical. For unique anatomical, histological, immunological properties underpinning its permeable dynamics, BBB regarded biomarker associated with neural pathogenesis. The permeability mice rats caused by GM dysbiosis raises question how metabolites change causes pathophysiology neuroinflammation neurodegeneration (NF&ND) aging, pivotal multidisciplinary field tightly immune chronic inflammation. If all, microbiota-induced inflammation (GM-SCI) mainly refers excessive mucosal immunity dysregulation, which is often influenced dietary components age, produced at interface intestinal (IB) or exacerbated after IB disruption, initiates various common diseases along dispersal routes, eventually impairs integrity cause NF&ND aging. To illustrate roles affected inflammatory “leaky” resulting their metabolites, we reviewed selected publications, including role barrier, influences on permeability, NF&ND, add depth bridging inflammation, plausible mechanism indispensable for corruption was highlighted; namely, maintenance cues cytokines, may help understand play major

Language: Английский

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Gut microbiome of multiple sclerosis patients and paired household healthy controls reveal associations with disease risk and course

Cell, Journal Year: 2022, Volume and Issue: 185(19), P. 3467 - 3486.e16

Published: Sept. 1, 2022

Language: Английский

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Multiple sclerosis

The Lancet, Journal Year: 2023, Volume and Issue: 403(10422), P. 183 - 202

Published: Nov. 7, 2023

Language: Английский

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Ageing and multiple sclerosis

The Lancet Neurology, Journal Year: 2022, Volume and Issue: 22(1), P. 66 - 77

Published: Oct. 7, 2022

Language: Английский

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Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1309 - 1327

Published: March 1, 2023

Language: Английский

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The role of the gut microbiota in multiple sclerosis

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(9), P. 544 - 558

Published: Aug. 5, 2022

Language: Английский

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Lactobacillus reuteri tryptophan metabolism promotes host susceptibility to CNS autoimmunity

Microbiome, Journal Year: 2022, Volume and Issue: 10(1)

Published: Nov. 23, 2022

Dysregulation of gut microbiota-associated tryptophan metabolism has been observed in patients with multiple sclerosis. However, defining direct mechanistic links between this apparent metabolic rewiring and individual constituents the microbiota remains challenging. We others have previously shown that colonization commensal putative probiotic species, Lactobacillus reuteri, unexpectedly enhances host susceptibility to experimental autoimmune encephalomyelitis (EAE), a murine model To identify underlying mechanisms, we characterized genome L. reuteri isolates, coupled vitro vivo metabolomic profiling, modulation dietary substrates, manipulation.

Language: Английский

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Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 31(2), P. 288 - 304.e8

Published: Feb. 1, 2023

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained debilitating fatigue, cognitive dysfunction, gastrointestinal disturbances, and orthostatic intolerance. Here, we report a multi-omic analysis of geographically diverse cohort 106 cases 91 healthy controls that revealed differences in gut microbiome diversity, abundances, functional pathways, interactions. Faecalibacterium prausnitzii Eubacterium rectale, which are both recognized as abundant, health-promoting butyrate producers the human gut, were reduced ME/CFS. Functional metagenomics, qPCR, metabolomics fecal short-chain fatty acids confirmed deficient microbial capacity for synthesis. Microbiome-based machine learning classifier models robust to geographic variation generalizable validation cohort. The abundance was inversely associated with severity. These findings demonstrate nature dysbiosis underlying network disturbance ME/CFS, providing possible targets disease classification therapeutic trials.

Language: Английский

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Dysbiosis of Gut Microbiota from the Perspective of the Gut–Brain Axis: Role in the Provocation of Neurological Disorders

Metabolites, Journal Year: 2022, Volume and Issue: 12(11), P. 1064 - 1064

Published: Nov. 3, 2022

The gut-brain axis is a bidirectional communication network connecting the gastrointestinal tract and central nervous system. keeps track of activities integrates them to connect gut health higher cognitive parts brain. Disruption in this connection may facilitate various neurological problems. Neurodegenerative diseases are characterized by progressive dysfunction specific populations neurons, determining clinical presentation. Misfolded protein aggregates that cause cellular toxicity aid collapse proteostasis defining characteristic neurodegenerative proteinopathies. These disorders not only caused changes neural compartment but also due other factors non-neural origin. Mounting data reveal majority (GI) physiologies mechanics governed system (CNS). Furthermore, microbiota plays critical role regulation physiological function brain, although mechanism involved has yet been fully interpreted. One emerging explanations start progression many illnesses dysbiosis microbial makeup. present understanding literature surrounding relationship between intestinal emergence certain diseases, such as Alzheimer's disease, Parkinson's Huntington's multiple sclerosis, main emphasis review. potential entry pathway pathogen-associated secretions toxins into CNS explored article at outset neuropathology. We have included possible undelaying synergistic effect infections, their metabolites, interactions based on current understanding.

Language: Английский

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