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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Diets intervene osteoporosis via gut-bone axis

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

Published: Jan. 4, 2024

Osteoporosis is a systemic skeletal disease that seriously endangers the health of middle-aged and older adults. Recently, with continuous deepening research, an increasing number studies have revealed gut microbiota as potential target for osteoporosis, research concept gut-bone axis has gradually emerged. Additionally, intake dietary nutrients adoption patterns may affect microbiota, alterations in might also influence metabolic status host, thus adjusting bone metabolism. Based on axis, can participate modulation metabolism by altering abundance, diversity, composition microbiota. Herein, combined emerging literatures relevant studies, this review aimed to summarize impacts different components osteoporosis acting well underlying mechanisms proper recommendations.

Language: Английский

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Impact of the Ketogenic Diet on Neurological Diseases: A Review

Life, Journal Year: 2025, Volume and Issue: 15(1), P. 71 - 71

Published: Jan. 9, 2025

The ketogenic diet (KD), high in fat and low carbohydrates, was introduced the 1920s as a non-pharmacological treatment for refractory epilepsy. Although its mechanism of action is not fully understood, beneficial effects have been observed neurological diseases such epilepsy, Alzheimer's disease, Parkinson's disease. This review examines impact molecular neuroglial complementary therapy diseases. KD associated with neuroprotective antioxidant that improve mitochondrial function, regulate neurotransmitter flow, reduce neuroinflammation oxidative stress. Glial cells play an essential role utilization ketone bodies (KBs) within central nervous system's metabolism, particularly during ketosis induced by KD. Thus, represents broad promising strategy involves both neurons glial cells, on brain metabolism neuroinflammatory homeostasis. Multiple mechanisms identified to explain benefits diseases; however, further experimental clinical studies are needed address various pathways order achieve conclusive results.

Language: Английский

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Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 124 - 124

Published: Dec. 21, 2023

Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA extrahepatic tissues, entering tricarboxylic acid cycle electron transport chain for ATP production. Reduced metabolism mitochondrial dysfunction correlate with increased neuronal death brain damage cerebral ischemia neurodegeneration. Both KBs ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes metabolic signaling functions. They enhance function, mitigate oxidative stress apoptosis, regulate epigenetic post-translational modifications of histones non-histone proteins. Additionally, KD contribute to reducing neuroinflammation modulating autophagy, neurotransmission systems, gut microbiome. This review aims explore current understanding molecular mechanisms underpinning against neurodegenerative diseases, including Alzheimer’s disease Parkinson’s disease.

Language: Английский

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Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 16, 2023

Abstract The ketogenic diet (KD) is a low‐carbohydrate, high‐fat regime that protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mouse model PD was fed with for 8 weeks. Motor function dopaminergic neurons were evaluated. Inflammation in brain, plasma, colon tissue also measured. Fecal samples assessed by 16S rDNA gene sequencing untargeted metabolomics. We found protected motor dysfunction, neuron loss, inflammation an MPTP PD. revealed administration significantly increased Citrobacter , Desulfovibrio Ruminococcus decreased Dubosiella whereas treatment reversed dysbiosis. Meanwhile, regulated MPTP‐induced histamine, N‐acetylputrescine, d ‐aspartic acid, other metabolites. microbiota transplantation using feces from KD‐treated mice attenuated impairment loss antibiotic‐pretreated mice. Our current study demonstrates played neuroprotective role through diet–gut microbiota–brain axis, which may involve brain colon. future research warranted to explore explicit anti‐inflammatory gut–brain axis models KD.

Language: Английский

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The gut microbiota–brain axis in neurological disorders

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 20, 2024

Abstract Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as microbiota–gut–brain axis (MGBA). The MGBA influences host's nervous system development, emotional regulation, cognitive function through neurotransmitters, immune modulation, metabolic pathways. Factors like diet, lifestyle, genetics, environment shape composition together. Most research explored how regulates host physiology its potential in preventing treating neurological disorders. However, individual heterogeneity of microbiota, strains playing dominant role diseases, interactions these microbial metabolites with central/peripheral systems still need exploration. This review summarizes driving neurodevelopmental disorders (autism spectrum disorder attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's Parkinson's disease), mood (anxiety depression) recent years discusses current clinical preclinical microbe‐based interventions, including dietary intervention, probiotics, prebiotics, fecal transplantation. It also puts forward insufficient on provides framework for further

Language: Английский

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Therapeutic Potential of the Ketogenic Diet: A Metabolic Switch with Implications for Neurological Disorders, the Gut-Brain Axis, and Cardiovascular Diseases

The Journal of Nutritional Biochemistry, Journal Year: 2024, Volume and Issue: 132, P. 109693 - 109693

Published: June 15, 2024

Language: Английский

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Ketones on the Brain: Can Diet Help Turn the Tables on Parkinson's?—Commentary on Mahajan et al. (2024)

European Journal of Neuroscience, Journal Year: 2025, Volume and Issue: 61(3)

Published: Feb. 1, 2025

While disease-modifying therapeutics for Parkinson's disease (PD) remain elusive, lifestyle changes are promising but often overlooked options diminishing symptoms and slowing progression. Ketogenic diet (KD), first touted a century ago as treatment epilepsy, has shown encouraging signs an alternative therapy idiopathic PD (Vanitallie et al. 2005). Deficits in neuronal metabolism central contributors to many neurodegenerative diseases (Yang, Park, Lu 2023), patients with exhibit deficiencies mitochondrial complex I function (González-Rodríguez 2021). Neurons capable of oxidizing ketone bodies energy source that can bypass I, providing potential mechanism boost production the face poorly functioning mitochondria (Tieu 2003). Pre-clinical studies using inhibitor 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) demonstrate KD prevent motor dysfunction dopaminergic degeneration associated this model (Jiang 2023; Yang Cheng 2010; Zhang 2023). Exposure prior MPTP or lipopolysaccharide promotes neuroprotective anti-inflammatory effects brain (Fu 2015; 2010), attenuates glial activation beneficial gut microbiota In recent issue EJN, Mahajan colleagues (Mahajan 2024) expanded on work by exploring two questions: (1) Could ketone-rich be useful intervention progressive genetic PD? (2) Can supplementation when given post-symptomatically? To accomplish this, authors used phenotypically-faithful MitoPark mouse PD, which is dopamine neuron-specific knockout transcription factor A (Tfam) (Ekstrand 2007). Tfam drives expression mitochondria-encoded genes including those essential respiratory chain function. This mimics several key aspects clinical progression, adult-onset age-dependent neurons substantia nigra pars compacta, producing catastrophic failure (Beckstead Howell When administered ester-enriched (KEED) mice beginning emergence obvious deficits, they observed substantial retention locomotion rotarod performance. was accompanied modest improvement striatal release, interestingly, no clear preservation themselves (i.e., survival). Further, some benefit also KEED initiated at later time point, following appearance symptoms, suggesting dietary interventions may even more advanced stages disease. The conclude mice, works enhancing preserving bioenergetics, synthesis vesicular packaging. symptoms. study did not directly test cellular mechanisms, data point compelling possibilities. rely heavily oxidative phosphorylation (OXPHOS) generate (Demetrius, Magistretti, Pellerin 2015), particularly susceptible their extensive axonal arbours, high calcium handling spontaneous firing constantly requires replenishment intracellular ion gradients. Distal axons neurodegeneration due compromised protein quality decreased ability maintain energetic homeostasis provided were apparently able act effective substrate stress (Zhang Furthermore, body β-Hydroxybutyrate (βHB) been previously protect from ATP manner dependent II Another suggested increase enhanced availability tetrahydrobiopterin (BH4), serves co-factor tyrosine hydroxylase catecholamines (Nagatsu 2024). enter TCA cycle, NADPH turn contributes BH4 (Soula 2020). could therefore strategy declining while potentially increasing surviving neurons. Finally, administration likely alters its metabolites ameliorating parkinsonian through regulation gut-brain axis. Despite showing promise, challenges yet derail regular use KDs improve life patients. Strict regimes difficult implement have low compliance, prolonged induce side such increased LDL levels (Veech 2001). Additionally, additional challenges, movement difficulties hinder food preparation, loss smell reduce palatability, constipation common worsened fibre KD. Although large, long-term conducted, one feasibility showed help dietician, 5 out 7 prepare adhere Age leading risk aging itself produce compensatory OXPHOS proteins (Stauch, Purnell, Fox 2014), priming cells supply ketones. contrast, suggests actually undergo Warburg-type metabolic shift favours glycolysis over If occurs during it would limit window treatment. these barriers, results multiple other encouragingly support day critical part holistic least subset worthy further study. Strategies capacity value prolonging ketones PD. Ana Luiza Drumond-Bock: conceptualization, writing – original draft, review editing. Michael J. Beckstead: funding acquisition, We like thank Scott Plafker, Kendra Plafker Amanda Sharpe helpful discussions. funded NIH R01 NS135830. declare conflicts interest. peer history article available https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/ejn.70025. No preparation commentary.

Language: Английский

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Unrevealing the molecular mechanisms of MPTP-induced Parkinson’s in experimental animals

Medicinal Chemistry Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Language: Английский

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Energy Metabolism and Brain Aging: Strategies to Delay Neuronal Degeneration

Cellular and Molecular Neurobiology, Journal Year: 2025, Volume and Issue: 45(1)

Published: April 21, 2025

Abstract Aging is characterized by a gradual decline in physiological functions, with brain aging being major risk factor for numerous neurodegenerative diseases. Given the brain’s high energy demands, maintaining an adequate ATP supply crucial its proper function. However, advancing age, mitochondria dysfunction and deteriorating metabolism lead to reduced overall production impaired mitochondrial quality control (MQC). As result, promoting healthy has become key focus contemporary research. This review examines relationship between aging, highlighting connection MQC metabolism, proposes strategies delay targeting metabolism.

Language: Английский

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