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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The microbiome–gut–brain axis in Parkinson disease — from basic research to the clinic

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(8), P. 476 - 495

Published: June 24, 2022

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: A Novel Therapeutic Target for Parkinson’s Disease

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

Published: June 24, 2022

Parkinson’s disease (PD) is the second most common neurodegenerative characterized by motor dysfunction. Growing evidence has demonstrated that gut dysbiosis involved in occurrence, development and progression of PD. Numerous clinical trials have identified characteristics changed microbiota profiles, preclinical studies PD animal models indicated can influence onset via increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels α-synuclein fibrils, oxidative stress, decreasing neurotransmitter production. The be considered promising diagnostic therapeutic targets for PD, which regulated probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, fecal transplantation, diet modifications, Chinese medicine. This review summarizes recent PD-associated profiles functions, potential roles, mechanisms microbiota-targeted interventions Deciphering underlying roles will help interpret pathogenesis from new perspectives elucidate novel strategies

Language: Английский

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Gut microbiome, short-chain fatty acids, alpha-synuclein, neuroinflammation, and ROS/RNS: Relevance to Parkinson's disease and therapeutic implications

Redox Biology, Journal Year: 2024, Volume and Issue: 71, P. 103092 - 103092

Published: Feb. 16, 2024

In this review, we explore how short-chain fatty acids (SCFAs) produced by the gut microbiome affect Parkinson's disease (PD) through their modulatory interactions with alpha-synuclein, neuroinflammation, and oxidative stress mediated reactive oxygen nitrogen species (ROS/RNS). particular, SCFAs-such as acetate, propionate, butyrate-are involved in gut-brain communication can modulate alpha-synuclein aggregation, a hallmark of PD. The patients PD has lower levels SCFAs than healthy individuals. Probiotics may be potential strategy to restore alleviate symptoms, but underlying mechanisms are not fully understood. Also discuss present guts brains PD, induce neuroinflammation via ROS/RNS. Alpha-synuclein is considered an early biomarker for link axis pathogenesis. Therefore, elucidating role impact on alpha-synuclein-induced microglia ROS/RNS crucial pathogenesis treatment.

Language: Английский

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The microbiota–gut–brain axis in Huntington's disease: pathogenic mechanisms and therapeutic targets

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Huntington's disease (HD) is a currently incurable neurogenerative disorder and typically characterized by progressive movement (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which depression), peripheral symptoms gastrointestinal dysfunction). There are no approved disease‐modifying therapies available for HD, with death usually occurring approximately 10–25 years after onset, but some hold promising potential. HD subjects often burdened chronic diarrhea, constipation, esophageal gastric inflammation, susceptibility to diabetes. Our understanding the microbiota–gut–brain axis its infancy growing evidence from preclinical clinical studies suggests role gut microbial population imbalance (gut dysbiosis) pathophysiology. The brain can communicate through enteric nervous system, immune vagus nerve, microbiota‐derived‐metabolites including short‐chain fatty acids, bile branched‐chain amino acids. This review summarizes supporting demonstrating alterations bacterial fungal composition that may be associated HD. We focus on mechanisms dysbiosis compromise health, thus triggering neuroinflammatory responses, further highlight outcomes attempts modulate microbiota as therapeutic strategies Ultimately, we discuss dearth data need more longitudinal translational this nascent field. suggest future directions improve our association between microbes pathogenesis other ‘brain body disorders’.

Language: Английский

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Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: July 27, 2022

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative attributed to synergistic effects of genetic risk and environmental stimuli. Although PD characterized by motor dysfunction resulting from intraneuronal alpha-synuclein accumulations, termed Lewy bodies, dopaminergic neuronal degeneration in substantia nigra, multiple systems are involved process, heterogenous clinical presentation progression. Genetic predisposition regarding aberrant immune responses, abnormal protein aggregation, autophagolysosomal impairment, mitochondrial leads vulnerable neurons that sensitive triggers and, together, result degeneration. Neuropathology studies have shown that, at least some patients, bodies start enteric nervous system then spread central through gut–brain axis, suggesting contribution an altered gut microenvironment pathogenesis PD. A plethora evidence has revealed different microbiomes metabolites patients with compared unaffected controls. Chronic inflammation impaired intestinal barrier integrity been observed human mouse models These observations led hypothesis a potential trigger process genetically susceptible host. In this review, we will discuss complex interplay between factors microenvironmental changes contributing pathogenesis.

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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A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Nov. 8, 2022

Parkinson's disease (PD) is a movement disorder characterized by neuroinflammation, α-synuclein pathology, and neurodegeneration. Most cases of PD are non-hereditary, suggesting strong role for environmental factors, it has been speculated that may originate in peripheral tissues such as the gastrointestinal (GI) tract before affecting brain. The gut microbiome altered impact motor GI symptoms indicated animal studies, although mechanisms gut-brain interactions remain incompletely defined. Intestinal bacteria ferment dietary fibers into short-chain fatty acids, with fecal levels these molecules differing between healthy controls mouse models. Among other effects, microbial metabolites can modulate activation microglia, brain-resident immune cells implicated PD. We therefore investigated whether fiber-rich diet influences microglial function overexpressing (ASO) mice, preclinical model PD-like pathology. Feeding prebiotic high-fiber attenuates deficits reduces aggregation substantia nigra mice. Concomitantly, ASO mice adopts profile correlated health upon treatment, which also activation. Single-cell RNA-seq analysis microglia from striatum uncovers increased pro-inflammatory signaling reduced homeostatic responses compared to wild-type counterparts on standard diets. However, feeding reverses pathogenic states promotes expansion protective disease-associated macrophage (DAM) subsets microglia. Notably, depletion using CSF1R inhibitor eliminates beneficial effects prebiotics restoring despite diet. These studies uncover novel microglia-dependent interaction findings have implications neuroinflammation

Language: Английский

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Boundaries and integration between microbiota, the nervous system, and immunity

Immunity, Journal Year: 2023, Volume and Issue: 56(8), P. 1712 - 1726

Published: Aug. 1, 2023

Language: Английский

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