Storage of the vital metal tungsten in a dominant SCFA-producing human gut microbe Eubacterium limosum and implications for other gut microbes

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

ABSTRACT Enzymes containing tungsten rather than the ubiquitous and analogous element molybdenum are prevalent in human gut microbiome, especifically microbes that contribute to overall health. Eubacterium limosum is a dominant organism whose production of beneficial short-chain fatty acids (SCFAs) from lactate involves tungstoenzymes. Here, we characterized E. Tub, storage protein. Tub has sub-nanomolar affinity for tungstate contains single TOBE domain first molybdate Crystal structures revealed assembles as hexamer composed trimer dimers, capable binding eight oxyanions at two distinct sites located inter-subunit interfaces. Tungstate-saturated exhibited unusually high thermal chemical stability. Glucose-grown accumulates low levels tungstoenzymes, termed WOR1 FDH, which oxidize aldehydes formate, respectively. Lactate-grown cells contain concentrations these tungstoenzymes where FDH involved converting SCFAs. appear accumulate preparation availability gut. other TOBE-containing proteins widespread gene co-occurrence analysis predicts there comparable numbers bind molybdate. The results with represent an important step understanding mechanisms within general. IMPORTANCE Tungsten metabolism was found be detoxification food antimicrobial aldehydes, well In this study, protein microbe, , stores its use enzymes SCFA generation. This several families also transport tungstate-dependent regulation widely distributed microbiome. Elucidating how stored transported contributes our microbiome impact on

Language: Английский

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Could a Mediterranean Diet Modulate Alzheimer’s Disease Progression? The Role of Gut Microbiota and Metabolite Signatures in Neurodegeneration

Foods, Journal Year: 2025, Volume and Issue: 14(9), P. 1559 - 1559

Published: April 29, 2025

Neurodegenerative disorders such as Alzheimer’s disease (AD), the most common form of dementia, represent a growing global health crisis, yet current treatment strategies remain primarily palliative. Recent studies have shown that neurodegeneration through complex interactions within gut–brain axis largely depends on gut microbiota and its metabolites. This review explores intricate molecular mechanisms linking dysbiosis to cognitive decline, emphasizing impact microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, tryptophan neuroinflammation, blood–brain barrier (BBB) integrity, amyloid-β tau pathology. The paper highlights major microbiome signatures associated with disease, detailing their metabolic pathways inflammatory crosstalk. Dietary interventions promise in modulating composition, potentially mitigating neurodegenerative processes. critically examines influence dietary patterns, Mediterranean Western diets, microbiota-mediated neuroprotection. Bioactive compounds like prebiotics, omega-3 polyphenols exhibit neuroprotective effects by reducing neuroinflammation. Furthermore, it discusses emerging microbiome-based therapeutic strategies, probiotics, postbiotics, fecal transplantation (FMT), potential for slowing progression. Despite these advances, several knowledge gaps remain, interindividual variability responses need large-scale, longitudinal studies. study proposes an integrative, precision medicine approach, incorporating science into paradigms. Ultimately, cognizance at mechanistic level could unlock novel avenues, offering non-invasive, diet-based strategy managing improving health.

Language: Английский

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Potential Application of MicroRNAs and Some Other Molecular Biomarkers in Alzheimer’s Disease

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(6), P. 5066 - 5084

Published: May 22, 2024

Alzheimer’s disease (AD) is the world’s most common neurodegenerative disease, expected to affect up one-third of elderly population in near future. Among major challenges combating AD are inability reverse damage caused by expensive diagnostic tools, and lack specific markers for early detection AD. This paper highlights promising research directions molecular diagnosis, including potential microRNAs. The latest methods diagnosing discussed, with particular emphasis on techniques prior appearance full symptoms detectable human body fluids. A collection recent studies demonstrates using miRNAs as biomarkers. Up- or downregulation diseases may not only provide a new tool but also serve marker differentiating diseases. However, further this direction needed.

Language: Английский

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The Gut Microbiome-Neuroglia Axis: Implications for Brain Health, Inflammation, and Disease

Neuroglia, Journal Year: 2024, Volume and Issue: 5(3), P. 254 - 273

Published: Aug. 1, 2024

The human central nervous system is convolutedly connected to the gut microbiome, a diverse community of microorganisms residing in gastrointestinal tract. Recent research has highlighted bidirectional communication between microbiome and neuroglial cells, which include astrocytes, microglia, oligodendrocytes, ependymal cells. These cells are essential for maintaining CNS homeostasis, supporting neuronal function, responding pathological conditions. This review examines interactions neuroglia, emphasizing their critical roles brain health development neurological disorders. Dysbiosis, or imbalance been associated with various psychiatric conditions, such as autism spectrum disorder, anxiety, depression, neurodegenerative diseases like Alzheimer’s Parkinson’s. influences function through microbial metabolites, immune modulation, neuroinflammatory responses. Understanding these paves way new therapeutic targets strategies preventing treating scoping aims highlight mechanisms microbiome-neuroglia axis its potential target.

Language: Английский

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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

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Oral Administration of Probiotic Bacteria Alleviates Tau Phosphorylation, Aβ Accumulation, Microglia Activation, and Memory Loss in 5xFAD Mice

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(3), P. 208 - 208

Published: Feb. 23, 2024

The gut–brain axis (GBA) plays a significant role in various neurodegenerative disorders, such as Alzheimer’s disease (AD), and the gut microbiome (GM) can bidirectionally communicate with brain through GBA. Thus, recent evidence indicates that GM may affect pathological features progression of AD humans. aim our study was to elucidate impact probiotics on 5xFAD model. Probiotics (Bifidobacterium lactis, Levilactobacillus brevis, Limosilactobacillus fermentum) were orally administered mice modify composition. Additionally, freeze-dried food containing phosphatidylserine used positive control. Behavioral pathogenesis assessed cross maze Morris water tests. Our findings revealed probiotic administration resulted improvements spatial recognition memories. Furthermore, neuroprotective effects substantiated by reduction amyloid-β accumulation critical regions. Microglial activation also attenuated hippocampus cerebral cortex. Moreover, elevated tau phosphorylation ameliorated probiotics-treated group. results highlight potential use intervention AD.

Language: Английский

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Gut microbiota metabolites: potential therapeutic targets for Alzheimer’s disease?

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 17, 2024

Background Alzheimer’s disease (AD) is a neurodegenerative characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective preventing or mitigating the progression of AD. An increasing number recent studies support hypothesis that gut microbiome its metabolites may be associated with upstream regulators AD pathology. Methods In this review, we comprehensively explore potential mechanisms currently available targeting for improvement Our discussion structured around modern research advancements AD, bidirectional communication between brain, multi-target regulatory effects microbial on strategies aimed at modulating microbiota to manage Results The plays crucial role pathogenesis through continuous via microbiota-gut-brain axis. Among these, such as lipids, amino acids, bile acids neurotransmitters, especially sphingolipids phospholipids, serve central components gut-brain axis, regulating AD-related pathogenic including β-amyloid metabolism, Tau protein phosphorylation, neuroinflammation. Additionally, probiotic administration, fecal transplantation, antibiotic use have also provided evidence supporting association At same time, propose an innovative strategy treating AD: healthy lifestyle combined targeted probiotics other interventions, aiming restore intestinal ecology balance. Conclusion Despite previous efforts, molecular microbes act yet fully described. microorganisms become essential target connecting axis improving symptoms it requires joint exploration multiple centers disciplines.

Language: Английский

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Exploring the Potential of Probiotics in Alzheimer's disease and Gut Dysbiosis

IBRO Neuroscience Reports, Journal Year: 2024, Volume and Issue: 17, P. 441 - 455

Published: Nov. 8, 2024

Language: Английский

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The oral microbiome is associated with HPA axis response to a psychosocial stressor

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 9, 2024

Intense psychosocial stress during early life has a detrimental effect on health-disease balance in later life. Simultaneously, despite its sensitivity to stress, the developing microbiome contributes long-term health. Following exposure, HPA-axis activation regulates "fight or flight" response with release of glucose and cortisol. Here, we investigated interaction between oral response. We used cohort 115 adults, mean age 24, who either experienced institutionalisation adoption (n = 40) were non-adopted controls 75). Glucose cortisol measurements taken from participants following an extended socially evaluated cold pressor test (seCPT) at multiple time points. The cohort´s was profiled via 16S-V4 sequencing microbial DNA saliva buccal samples. Using mixed-effect linear regressions, identified 12 genera that exhibited host's cortisol-glucose strongly influencing intensity clearance exposure. Particularly, taxa influenced profiles kinetics seCPT In conclusion, our study provided evidence for modifying human metabolism, as shown glucose-cortisol series data.

Language: Английский

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Revisiting the role of phospholipases in alzheimer’s: crosstalk with processed food

Critical Reviews in Food Science and Nutrition, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 19

Published: July 13, 2024

Phospholipases such as phospholipase-A, phospholipase-B, phospholipase-C and phospholipase-D are important functional enzymes of the cell membrane responsible for a variety functions signal transduction, production lipid mediators, metabolite digestion playing pathological role in central nervous system diseases. have shown an association with Alzheimer's disease these found correlation several metabolic pathways that can lead to activation inflammatory signals via astrocytes microglial cells. We also highlighted unhealthy practices like smoking consuming processed foods, rich nitroso compounds phosphatidic acid, which contribute neuronal damage AD through phospholipases. A few therapeutic approaches use inhibitors phospholipase-D,phospholipase A2 well autophagy-mediated inhibition been discussed control onset AD. This paper serves crosstalk between phospholipases their neurodegenerative influence on other biomolecules membranes, acquired diets possible methods treat anomalies occurring due disorder involving acting major signaling molecules.

Language: Английский

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