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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Ruminococcus gnavus: friend or foe for human health

FEMS Microbiology Reviews, Journal Year: 2023, Volume and Issue: 47(2)

Published: March 1, 2023

Abstract Ruminococcus gnavus was first identified in 1974 as a strict anaerobe the gut of healthy individuals, and for several decades, its study has been limited to specific enzymes or bacteriocins. With advent metagenomics, R. associated both positively negatively with an increasing number intestinal extraintestinal diseases from inflammatory bowel neurological disorders. This prompted renewed interest understanding adaptation mechanisms gut, molecular mediators affecting association health disease. From ca. 250 publications citing since 1990, 94% were published last 10 years. In this review, we describe biological characterization gnavus, occurrence infant adult microbiota factors influencing colonization gastrointestinal tract; also discuss current state our knowledge on role host We highlight gaps hypothesis that differential outcomes are strain niche specific.

Language: Английский

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Gut bacterial profiles in Parkinson's disease: A systematic review

CNS Neuroscience & Therapeutics, Journal Year: 2022, Volume and Issue: 29(1), P. 140 - 157

Published: Oct. 25, 2022

Abstract Introduction Recent advances have highlighted the relationships between gut dysbiosis and Parkinson's disease (PD). Microbiota transplantation from PD patients to mice can induce increased alpha‐synuclein‐mediated motor deficits. Human studies identified differences in microbiota of compared healthy controls. We undertook a systematic review evaluate available evidence for involvement bacteria etiology PD. Methods The PubMed databank, China National Knowledge Infrastructure Wanfang Data were searched inception until June 2021 identify human case–control that investigated quantified feces. evaluated resulting focusing on bacterial taxa different Results Twenty‐six found which 53 microbial families 98 genera exhibited with by more than two as Bifidobacterium , Alistipes Christensenella Enterococcus Oscillospira Bilophila Desulfovibrio Escherichia/Shigella Akkermansia while Prevotella Blautia Faecalibacterium Fusicatenibacter Haemophilus had three or reports being lower patients. More one report demonstrated Bacteroides Odoribacter Parabacteroides Butyricicoccus Butyrivibrio Clostridium Coprococcus Lachnospira Lactobacillus Megasphaera Phascolarctobacterium Roseburia Ruminococcus Streptococcus Klebsiella altered both directions. Conclusion Our shows microbiome may involve alterations short‐chain fatty acids (SCFAs)‐producing an increase putative pathobionts. SCFAs‐producing vary above below “optimal range,” causing imbalances. Considering are beneficial health, be associated medications, especially COMT inhibitors, high level aging.

Language: Английский

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Gut microbiota remodeling improves natural aging-related disorders through Akkermansia muciniphila and its derived acetic acid

Pharmacological Research, Journal Year: 2023, Volume and Issue: 189, P. 106687 - 106687

Published: Feb. 4, 2023

Accumulating evidence indicates gut microbiota contributes to aging-related disorders. However, the exact mechanism underlying dysbiosis-related pathophysiological changes during aging remains largely unclear. In current study, we first performed remodeling on old mice by fecal transplantation (FMT) from young mice, and then characterized bacteria signature that was specifically altered FMT. Our results revealed FMT significantly improved natural systemic disorders, particularly exerted hepatoprotective effects, glucose sensitivity, hepatosplenomegaly, inflammaging, antioxidative capacity intestinal barrier. Moreover, increased abundance of A.muciniphila, which almost nondetectable in mice. Interestingly, A.muciniphila supplementation also similar benefits with Notably, targeted metabolomics short chain fatty acids (SCFAs) only acetic acid consistently reversed Then, intervention beneficial actions both Caenorhabditis elegans conclusion, our study demonstrated disorders through its derived acid, suggesting interventions potent stimulative A. muciniphila growth production alternative effective way maintain healthy aging. The data RNAseq 16 S rRNA gene sequencing can be accessed NCBI accession number PRJNA848996 PRJNA849355.

Language: Английский

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Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 27, 2024

The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS) Huntington's (HD), are complex multifaceted. A growing body evidence suggests that the gut microbiome plays crucial roles in development progression diseases. Clinicians have come to realize therapeutics targeting potential halt This narrative review examines alterations AD, PD, ALS HD, highlighting close relationship between brain Processes mediate microbiome-brain communication including immunological, vagus nerve circulatory pathways, evaluated. Furthermore, we summarize for diseases modify its metabolites, diets, probiotics prebiotics, microbial antibacterials faecal transplantation. Finally, current challenges future directions discussed.

Language: Английский

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Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson's disease: A bench-to-bedside translational approach

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 270 - 282

Published: Jan. 9, 2024

Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in genus Blautia and reduction fecal short-chain fatty acid (SCFA) butyrate level PD patients compared healthy controls. The abundance of correlated with severity PD. Supplementation butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation dopaminergic neuronal death mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, RAS-related modulated by butyrate, emerged as key mechanism inhibiting microglial activation change RAS-NF-κB pathway was observed. Furthermore, producta-derived inhibition through regulation pathway. These findings elucidate causal relationship between PD, presenting novel microbiota-based treatment perspective for

Language: Английский

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The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12289 - 12289

Published: Oct. 14, 2022

The bidirectional interaction between the gut microbiota (GM) and Central Nervous System, so-called brain axis (GMBA), deeply affects function has an important impact on development of neurodegenerative diseases. In Parkinson’s disease (PD), gastrointestinal symptoms often precede onset motor non-motor manifestations, alterations in GM composition accompany pathogenesis. Several studies have been conducted to unravel role dysbiosis intestinal permeability PD progression, but therapeutic diagnostic applications modifying approaches remain be fully elucidated. After a brief introduction involvement GMBA disease, we present evidence for leaky patients. According these data, then review potential GM-based signatures serve as biomarkers highlight emerging probiotics, prebiotics, antibiotics, dietary interventions, fecal transplantation supportive PD. Finally, analyze mutual influence commonly prescribed medications gut-microbiota, offer insights also nasal oral pathology, thus providing comprehensive up-to-date overview microbial features diagnosis treatment.

Language: Английский

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Gut microbiota bridges the iron homeostasis and host health

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(9), P. 1952 - 1975

Published: July 27, 2023

Language: Английский

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Fecal Microbiota Transplantation for Treatment of Parkinson Disease

JAMA Neurology, Journal Year: 2024, Volume and Issue: 81(9), P. 925 - 925

Published: July 29, 2024

Importance Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) shown promising effects preclinical PD models. Objective To assess the safety symptomatic efficacy of colonic single-dose anaerobically prepared FMT. Design, Setting, Participants This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 June 2023 with follow-up period 12 months at 4 hospitals Finland. Patients aged 35 to 75 years Hoehn & Yahr stage 1-3 mild moderate symptom burden dysbiosis were included. Of 229 patients screened, 48 47 received intervention. One patient discontinued due worsening symptoms. Two further excluded before analysis 45 included intention-to-treat analysis. Intervention 2:1 ratio receive FMT or placebo via colonoscopy. Main Outcomes Measures The primary end point change Movement Disorder Society Unified Parkinson’s Disease Rating Scale parts I-III (part III off medication) 6 months. Safety assessed by recording adverse events (AEs). Results median (IQR) age 65 (52.5-70.0) group 66 (59.25-69.75) group; 9 (60.0%) 16 (53.3%) male group, respectively. outcome did not differ groups (0.97 points, 95% CI, −5.10 7.03, P = .75). Gastrointestinal AEs more frequent (16 [53%] vs 1 [7%]; .003). Secondary outcomes post hoc analyses showed stronger increase dopaminergic medication improvement certain motor nonmotor group. Microbiota changes pronounced after but differed donor. Nevertheless, status reversed frequently Conclusions Relevance safe offer clinically meaningful improvements. Further studies—for example, through modified approaches bowel cleansing—are warranted regarding specific impact donor composition conversion on as well needs PD. Trial Registration ClinicalTrials.gov Identifier: NCT04854291

Language: Английский

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Akkermansia muciniphila Is Beneficial to a Mouse Model of Parkinson’s Disease, via Alleviated Neuroinflammation and Promoted Neurogenesis, with Involvement of SCFAs

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(3), P. 238 - 238

Published: Feb. 29, 2024

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson’s disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to unknown. To answer this question, mice received MPTP intraperitoneally construct subacute model and were then supplemented with orally 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, neurogenesis examined. In addition, intestinal inflammation, serum fecal short-chain fatty acids (SCFAs) analyses, assessed. We found treatment effectively inhibited reduction neurons substantia nigra pars compacta (SNpc) partially improved motor function mice. Additionally, markedly alleviated neuroinflammation striatum hippocampus promoted hippocampal neurogenesis. It also level colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations isovaleric acid levels, lower permeability. strongly neuroprotective agent therapy.

Language: Английский

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