Microbial Influences on Amyotrophic Lateral Sclerosis: The Gut–Brain Axis and Therapeutic Potential of Microbiota Modulation

Sclerosis, Journal Year: 2025, Volume and Issue: 3(1), P. 8 - 8

Published: March 5, 2025

Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive degeneration of motor neurons. The gut microbiota, community microorganisms in digestive tract, has recently been implicated ALS pathogenesis through its influence on neuroinflammation and metabolic pathways. This review explores potential role microbiota metabolites progression investigates therapeutic approaches targeting microbiota. Methods: A comprehensive current literature was conducted to assess relationship between composition, microbial metabolites, patients. We searched for published reports ALS, emphasizing complex interplay dysbiosis, neuroinflammation, systemic metabolism. Special emphasis placed studies exploring short-chain fatty acids (SCFAs), bacterial amyloids (curli-like factors), neurotoxins such as β-methylamino-L-alanine (BMAA). liver–gut axis evaluated well. changes would sustain rationale strategies probiotics, prebiotics, fecal transplantation (FMT), dietary interventions. Results: patients exhibit reduced SCFA-producing bacteria an increase potentially pathogenic genera. Of note, different do not agree common patterns being linked supporting need further, more extensive studies. Dysbiosis sometimes correlates with inflammation disrupted liver function, amplifying neuroinflammatory responses. Key including SCFAs, amyloids, BMAA, may exacerbate neuron promoting protein misfolding, oxidative stress, neuroinflammation. Emerging strategies, probiotics FMT, show restoring balance, although clinical data remain limited. Conclusions: could modulate metabolism ALS. Microbiota-targeted therapies, interventions, represent promising avenues mitigating disease progression. Further research required validate these interventions large-scale, longitudinal develop personalized microbiota-based treatments tailored individual phenotypes.

Language: Английский

---

Hydrogen Sulfide and Gut Microbiota: Their Synergistic Role in Modulating Sirtuin Activity and Potential Therapeutic Implications for Neurodegenerative Diseases

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(11), P. 1480 - 1480

Published: Nov. 4, 2024

The intricate relationship between hydrogen sulfide (H2S), gut microbiota, and sirtuins (SIRTs) can be seen as a paradigm axis in maintaining cellular homeostasis, modulating oxidative stress, promoting mitochondrial health, which together play pivotal role aging neurodegenerative diseases. H2S, gasotransmitter synthesized endogenously by specific acts potent modulator of function protecting against damage. Through sulfate-reducing bacteria, microbiota influences systemic H2S levels, creating link health metabolic processes. Dysbiosis, or an imbalance microbial populations, alter production, impair function, increase heighten inflammation, all contributing factors diseases such Alzheimer’s Parkinson’s. Sirtuins, particularly SIRT1 SIRT3, are NAD+-dependent deacetylases that regulate biogenesis, antioxidant defense, inflammation. enhances sirtuin activity through post-translational modifications, sulfhydration, activate pathways essential for mitigating damage, reducing longevity. SIRT1, example, deacetylates NF-κB, pro-inflammatory cytokine expression, while SIRT3 modulates key enzymes to improve energy metabolism detoxify reactive oxygen species (ROS). This synergy is profoundly influenced the levels and, turn, impacts activation. microbiota–H2S–sirtuin also regulating neuroinflammation, plays central pathogenesis Pharmacological interventions, including donors sirtuin-activating compounds (STACs), promise these synergistically, providing novel therapeutic approach conditions. suggests diversity optimal have far-reaching effects on brain health.

Language: Английский

---

Role of Microbiota-Derived Hydrogen Sulfide (H2S) in Modulating the Gut–Brain Axis: Implications for Alzheimer’s and Parkinson’s Disease Pathogenesis

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2670 - 2670

Published: Nov. 23, 2024

Microbiota-derived hydrogen sulfide (H2S) plays a crucial role in modulating the gut–brain axis, with significant implications for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. H2S is produced by sulfate-reducing bacteria gut acts critical signaling molecule influencing brain health via various pathways, including regulating inflammation, oxidative stress, immune responses. maintains barrier integrity at physiological levels prevents systemic which could impact neuroinflammation. However, has dual or Janus face, excessive production, often resulting from dysbiosis, can compromise intestinal exacerbate processes promoting neuroinflammation glial cell dysfunction. This imbalance linked to early pathogenesis of Parkinson’s diseases, where overproduction exacerbates beta-amyloid deposition, tau hyperphosphorylation, alpha-synuclein aggregation, driving neuroinflammatory responses neuronal damage. Targeting microbiota restore homeostasis through dietary interventions, probiotics, prebiotics, fecal transplantation presents promising therapeutic approach. By rebalancing microbiota-derived H2S, these strategies may mitigate neurodegeneration offer novel treatments underscoring axis maintaining central nervous system health.

Language: Английский

---

Novelties on Neuroinflammation in Alzheimer’s Disease–Focus on Gut and Oral Microbiota Involvement

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11272 - 11272

Published: Oct. 19, 2024

Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through microbiota–gut–brain axis, including Alzheimer’s disease (AD). This review aims to provide a comprehensive synthesis recent findings on involvement neuroinflammatory processes associated with AD, emphasizing novel insights therapeutic implications. reveals that dysbiosis AD patients’ is linked heightened peripheral central inflammatory responses. Specific bacterial taxa, such as Bacteroides Firmicutes gut, well Porphyromonas gingivalis cavity, are notably altered leading significant changes microglial activation cytokine production. Gut alterations increased intestinal permeability, facilitating translocation endotoxins like lipopolysaccharides (LPS) into bloodstream exacerbating by activating brain’s toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, short-chain fatty acids (SCFAs) amyloid peptides, can cross blood-brain barrier modulate While microbial amyloids may contribute amyloid-beta aggregation brain, certain SCFAs butyrate exhibit anti-inflammatory properties, suggesting potential avenue mitigate neuroinflammation. not only highlights critical pathology but also offers ray hope modulating could represent strategy for reducing slowing progression.

Language: Английский

---

Hydrogen Sulfide (H2S- or H2Sn-Polysulfides) in Synaptic Plasticity: Modulation of NMDA Receptors and Neurotransmitter Release in Learning and Memory

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3131 - 3131

Published: March 28, 2025

Hydrogen sulfide (H2S) has emerged as a pivotal gaseous transmitter in the central nervous system, influencing synaptic plasticity, learning, and memory by modulating various molecular pathways. This review examines recent evidence regarding how H2S regulates NMDA receptor function neurotransmitter release neuronal circuits. By synthesizing findings from animal cellular models, we investigate impacts of enzymatic production exogenous on excitatory currents, long-term potentiation, intracellular calcium signaling. Data suggest that interacts directly with subunits, altering excitability. Simultaneously, promotes neurotransmitters such glutamate GABA, shaping dynamics plasticity. Furthermore, reports indicate disruptions metabolism contribute to cognitive impairments neurodegenerative disorders, underscoring potential therapeutic value targeting H2S-mediated Although precise mechanisms H2S-induced changes strength remain elusive, growing body positions significant regulator formation processes. calls for more rigorous exploration into underpinnings paving way novel pharmacological interventions dysfunction.

Language: Английский

---

Linkage of circadian rhythm disruptions with Alzheimer’s disease and therapeutic interventions

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

---

Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential

Biology, Journal Year: 2025, Volume and Issue: 14(4), P. 435 - 435

Published: April 17, 2025

Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in area gut microbiome has highlighted it as critical contributor to MS pathogenesis. Changes commensal microbiota, or dysbiosis, have been shown affect immune homeostasis, leading elevated levels pro-inflammatory cytokines disruption gut–brain axis. In this review, we provide comprehensive overview interactions between microbiota MS, especially focusing on immunomodulatory actions such influencing T-cell balance control metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella Faecalibacterium) were suggested lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions including probiotics, prebiotics, fecal transplantation (FMT), dietary therapies normalize suppress inflammation are proven improve clinical benefits patients. Alterations represent opportunities for identifying biomarkers early diagnosis, progression treatment response monitoring. Further studies need be potentially address interplay genetic predispositions, environmental cues, composition get precise mechanisms axis MS. conclusion, plays role pathogenesis offers potential novel therapeutic approaches, providing promising avenue improving outcomes management.

Language: Английский

---

Integration of Multi-Omics Data and Machine Learning to Identify Antioxidant Biomarkers in Type 1 Diabetes

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

---