The Brain–Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(14), P. 4130 - 4130

Published: July 15, 2024

Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s (PD), are severe age-related disorders with complex multifactorial causes. Recent research suggests a critical link between neurodegeneration the gut microbiome, via gut–brain communication pathway. This review examines role of trimethylamine N-oxide (TMAO), microbiota-derived metabolite, in development AD PD, investigates its interaction microRNAs (miRNAs) along this bidirectional TMAO, which is produced from dietary metabolites like choline carnitine, has been linked to increased neuroinflammation, protein misfolding, cognitive decline. In AD, elevated TMAO levels associated amyloid-beta tau pathologies, blood–brain barrier disruption, neuronal death. can cross promote aggregation amyloid proteins. Similarly, affects alpha-synuclein conformation aggregation, hallmark PD. also activates pro-inflammatory pathways NF-kB signaling, exacerbating neuroinflammation further. Moreover, modulates expression various miRNAs that involved neurodegenerative processes. Thus, microbiome–miRNA–brain axis represents newly discovered mechanistic dysbiosis neurodegeneration. MiRNAs regulate key oxidative stress, death, contributing progression. As direct consequence, specific miRNA signatures may serve potential biomarkers for early detection monitoring PD aims elucidate interrelationships microbiota, trimethylamine-N-oxide (miRNAs), central nervous system, implications these connections diseases. context, an overview current neuroradiology techniques available studying animal models used investigate intricate pathologies will be provided. summary, bulk evidence supports concept modulating pathway through changes, manipulation and/or miRNA-based therapies offer novel approaches implementing treatment debilitating neurological disorders.

Language: Английский

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The Profound Influence of Gut Microbiome and Extracellular Vesicles on Animal Health and Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 4024 - 4024

Published: April 4, 2024

The animal gut microbiota, comprising a diverse array of microorganisms, plays pivotal role in shaping host health and physiology. This review explores the intricate dynamics microbiome animals, focusing on its composition, function, impact host–microbe interactions. composition intestinal microbiota animals is influenced by ecology, including factors such as temperature, pH, oxygen levels, nutrient availability, well genetic makeup, diet, habitat, stressors, husbandry practices. Dysbiosis can lead to various gastrointestinal immune-related issues impacting overall productivity. Extracellular vesicles (EVs), particularly exosomes derived from play crucial intercellular communication, influencing transporting bioactive molecules across barriers like brain barriers. Dysregulation gut–brain axis has implications for disorders highlighting potential microbiota-derived EVs disease progression. Therapeutic approaches modulate probiotics, prebiotics, microbial transplants, phage therapy, offer promising strategies enhancing performance. Studies investigating effects therapy have shown results, with improving food safety poultry production systems. Understanding complex interactions between provides valuable insights into mechanisms underlying their Further research this field essential developing effective therapeutic interventions management promote well-being animals.

Language: Английский

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The bilateral cross communication in microbiota-gut-brain axis as a promising therapeutic target for Alzheimer’s disease: a focus on neuroinflammation

Deleted Journal, Journal Year: 2025, Volume and Issue: 2(1)

Published: Feb. 11, 2025

Abstract The microbiota- gut-brain interaction is a fundamental aspect of the synergy between microbiota and host in accessing signaling pathways to modulate brain function behavior. bilateral cross-communication, which might be direct or indirect, within line axis becoming promising therapeutic target for central nervous system (CNS) disorders, including Alzheimer’s disease (AD). Dysbiosis creates an imbalance abundance pro-inflammatory anti-inflammatory species, species’ availability may vary based on type neurodegenerative diseases. final outcome (i.e., dysbiosis) follows similar approach, leading shift towards state gut, increased gut permeability, triggered peripheral inflammatory response consequently occurs. To fully exploit impact interventions AD, scientific investigations help understand complex neuroinflammatory mechanisms investigating potential modulating future therapies.

Language: Английский

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Extracellular vesicles from Lacticaseibacillus paracasei reduce neuroinflammation in hippocampus and restore some cognitive functions in hyperammonemic rats

Microbiological Research, Journal Year: 2025, Volume and Issue: 294, P. 128101 - 128101

Published: Feb. 14, 2025

Language: Английский

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Nanoplastics and Neurodegeneration in ALS

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(5), P. 471 - 471

Published: May 7, 2024

Plastic production, which exceeds one million tons per year, is of global concern. The constituent low-density polymers enable spread over large distances and micro/nano particles (MNPLs) induce organ toxicity via digestion, inhalation, skin contact. Particles have been documented in all human tissues including breast milk. MNPLs, especially weathered particles, can breach the blood–brain barrier, inducing neurotoxicity. This has non-human species, human-induced pluripotent stem cell lines. Within brain, MNPLs initiate an inflammatory response with pro-inflammatory cytokine oxidative stress generation reactive oxygen mitochondrial dysfunction. Glutamate GABA neurotransmitter dysfunction also ensues alteration excitatory/inhibitory balance favor reduced inhibition resultant neuro-excitation. Inflammation cortical hyperexcitability are key abnormalities involved pathogenic cascade amyotrophic lateral sclerosis (ALS) intricately related to mislocalization aggregation TDP-43, a hallmark ALS. Water many foods contain humans, ingestion main form exposure. Digestion plastics within gut alter their properties, rendering them more toxic, they cause microbiome dysbiosis dysfunctional gut–brain axis. recognized as trigger and/or aggravating factor for ALS associated long (years or decades) preclinical period neonates infants exposed through milk, milk substitutes, toys. endangers time intense neurogenesis establishment neuronal circuitry, setting stage development neurodegeneration later life. MNPL neurotoxicity should be considered yet unrecognized risk diseases.

Language: Английский

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Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington’s Disease

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1144 - 1144

Published: July 3, 2024

Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative characterized by involuntary movements, cognitive decline, executive dysfunction, neuropsychiatric conditions such as anxiety depression. It follows an autosomal dominant inheritance pattern. Thus, child who has parent with the mutated huntingtin (mHTT) gene 50% chance of developing disease. Since HTT protein involved in many critical cellular processes, including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, autophagy, its aberrant aggregates lead to disruption numerous pathways neurodegeneration. Essential heavy metals are vital at low concentrations; however, higher concentrations, they can exacerbate HD disrupting glial–neuronal communication and/or causing dysbiosis (disturbance gut microbiota, GM), both which neuroinflammation further Here, we discuss detail interactions iron, manganese, copper glial–neuron GM indicate how this knowledge may pave way for development new generation disease-modifying therapies HD.

Language: Английский

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Gut microbial metabolism in Alzheimer's disease and related dementias

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(6), P. e00470 - e00470

Published: Oct. 1, 2024

Multiple studies over the last decade have established that Alzheimer's disease and related dementias (ADRD) are associated with changes in gut microbiome. These alterations organismal composition result abundances of functions encoded by microbial community, including metabolic capabilities, which likely impact host mechanisms. Gut microbes access dietary components other molecules made produce metabolites can enter circulation cross blood-brain barrier (BBB). In recent years, several been or shown to influence pathways relevant ADRD pathology. include short chain fatty acids, secondary bile tryptophan derivatives (such as kynurenine, serotonin, tryptamine, indoles), trimethylamine/trimethylamine N-oxide. Notably, some these BBB various effects on brain, modulating release neurotransmitters neuronal function, inducing oxidative stress inflammation, impacting synaptic function. Microbial also central nervous system through immune, enteroendocrine, enteric pathways, perturbations turn function peripheral immune responses, well integrity, homeostasis neurogenesis, glial cell maturation activation. This review examines evidence supporting notion is influenced microbiota its metabolites. The potential therapeutic advantages for preventing treating discussed, highlighting their role developing new treatments.

Language: Английский

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Immune mechanisms and shared immune targets in neurodegenerative diseases

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Language: Английский

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Reverse engineering the Gut-Brain Axis and microbiome-metabolomics for symbiotic/pathogenic balance in neurodegenerative diseases

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Nov. 10, 2024

Deciphering the molecular communications along gut-brain axis can help in understanding pathophysiology of neurodegenerative diseases and exploiting gut microbiome for therapeutics. However, microbes their metabolites have a multifaceted role mediating both brain physiology pathology. There is lack how when this tipped what are those contributing factors, at local (gut) distal (neuronal) levels, that drive imbalance. Here we reviewed its context summarized different factors such as gut-microbial diversity, metabolites, native immune system integrity epithelial blood-brain barriers interconnected collectively define involvement gut-microbiome pathologies. It also underlines need multidisciplinary tools animal models to simultaneously reflect on many these better correlate with clinical observations data obtained from human biopsies fecal samples. Harnessing will herald paradigm shift medicine aging, emphasizing significance broader spectrum health disease.

Language: Английский

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Microbiome Dysbiosis as a Driver of Neurodegeneration: Insights into Alzheimer’s and Parkinson’s Diseases

Gastrointestinal Disorders, Journal Year: 2025, Volume and Issue: 7(2), P. 28 - 28

Published: April 2, 2025

Microbiome dysbiosis—an imbalance in gut microbial communities—has emerged as a critical factor the pathogenesis of neurological disorders, particularly Alzheimer’s and Parkinson’s diseases. This review examines role microbiota neurodegeneration, emphasizing how dysbiosis disrupts gut–brain communication through mechanisms such impaired permeability, systemic inflammation, neuroinflammation. The gastrointestinal central nervous systems interact bidirectionally, with metabolites like short-chain fatty acids playing pivotal maintaining brain health. Dysbiotic shifts composition can compromise blood–brain barrier, enabling inflammatory molecules to alter biochemistry potentially accelerate neurodegenerative processes. Additionally, this explores therapeutic strategies—including probiotics, prebiotics, dietary modifications—designed restore balance, reduce neuroinflammation, slow disease progression. Further research is essential refine microbiome-targeted therapies fully elucidate their potential managing

Language: Английский

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