Gut liver brain axis in diseases: the implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Дек. 6, 2023

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In past few decades, breakthrough progress has been made in gut liver brain axis, mainly through understanding its formation mechanism increasing treatment strategies. this review, we discuss various complex networks including barrier permeability, hormones, microbial metabolites, vagus nerve, neurotransmitters, immunity, toxic β-amyloid (Aβ) metabolism, epigenetic regulation gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet nanotechnology application regulate Besides, some special treatments targeting gut-liver include farnesoid X receptor (FXR) agonists, takeda G protein-coupled 5 (TGR5) glucagon-like peptide-1 (GLP-1) antagonists fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain embraces cognitive behavioral therapy (CBT), antidepressants tryptophan metabolism-related therapies. liver-brain contains Aβ future, better interactions will promote development novel preventative strategies discovery precise therapeutic targets multiple diseases.

Язык: Английский

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Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Авг. 30, 2023

Major depressive disorder (MDD) is a chronic, generally episodic and debilitating disease that affects an estimated 300 million people worldwide, but its pathogenesis poorly understood. The heritability estimate of MDD 30-40%, suggesting genetics alone do not account for most the risk major depression. Another factor known to associate with involves environmental stressors such as childhood adversity recent life stress. Recent studies have emerged show biological impact factors in other stress-related disorders mediated by variety epigenetic modifications. These modification alterations contribute abnormal neuroendocrine responses, neuroplasticity impairment, neurotransmission neuroglia dysfunction, which are involved pathophysiology MDD. Furthermore, marks been associated diagnosis treatment evaluation modifications holds promise further understanding heterogeneous etiology complex phenotypes MDD, may identify new therapeutic targets. Here, we review preclinical clinical findings, including DNA methylation, histone modification, noncoding RNA, RNA chromatin remodeling In addition, elaborate on contribution these mechanisms pathological trait variability depression discuss how can be exploited purposes.

Язык: Английский

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Recent advances on the molecular mechanisms of exercise-induced improvements of cognitive dysfunction

Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)

Опубликована: Фев. 27, 2023

Abstract Physical exercise is of great significance for maintaining human health. Exercise can provide varying degrees benefits to cognitive function at all stages life cycle. Currently, with the aging world’s population and increase expectancy, dysfunction has gradually become a disease high incidence, which accompanied by neurodegenerative diseases in elderly individuals. Patients often exhibit memory loss, aphasia weakening orientation once diagnosed, are unable have normal life. Cognitive largely affects physical mental health, reduces quality life, causes economic burden society. At present, most interventions aimed maintain current level delay deterioration cognition. In contrast, as nonpharmacological therapy advantages its nontoxicity, low cost universal application. The molecular mechanisms underlying effect on cognition complex, studies been extensively centered neural plasticity, direct target brain. addition, mitochondrial stability energy metabolism essential brain status. Meanwhile, organ-brain axis responds induces release cytokines related this review, we summarize latest evidence effects cognition, point out directions future research.

Язык: Английский

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Physical exercise mediates cortical synaptic protein lactylation to improve stress resilience

Cell Metabolism, Год журнала: 2024, Номер 36(9), С. 2104 - 2117.e4

Опубликована: Авг. 19, 2024

Язык: Английский

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Physical Exercise Prevented Stress‐Induced Anxiety via Improving Brain RNA Methylation

Advanced Science, Год журнала: 2022, Номер 9(24)

Опубликована: Июнь 1, 2022

Abstract Physical exercise is effective in alleviating mental disorders by improving synaptic transmission; however, the link between body endurance training and neural adaptation has not yet been completely resolved. In this study, authors investigated role of RNA N 6 ‐methyladenosine (m6A), an emerging epigenetic mechanism, improved resilience against chronic restraint stress. A combination molecular, behavioral, vivo recording data demonstrates exercise‐mediated restoration m6A mouse medial prefrontal cortex, whose activity potentiated to exert anxiolytic effects. Furthermore, it revealed that hepatic biosynthesis one methyl donor necessary for improve brain counteract environmental This novel liver‐brain axis provides explanation network changes upon new insights into diagnosis treatment anxiety disorders.

Язык: Английский

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Running from Stress: Neurobiological Mechanisms of Exercise-Induced Stress Resilience

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(21), С. 13348 - 13348

Опубликована: Ноя. 1, 2022

Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged be predisposing or precipitating factor in neuropsychiatric diseases. There clear relationship between disturbances induced by stressful stimuli, especially long-lasting and cognitive deficits rodent models affective disorders. Regular physical activity has positive effect on the central nervous system (CNS) functions, contributes an improvement mood abilities (including memory learning), correlated with increase expression neurotrophic factors markers synaptic plasticity as well reduction inflammatory factors. Studies published so far show that energy challenge caused exercise can affect CNS improving cellular bioenergetics, stimulating processes responsible for removal damaged organelles molecules, attenuating inflammation processes. brings another important benefit: increased robustness. The evidence from animal studies sedentary lifestyle associated vulnerability, whereas physically active resilience. Here, we have performed comprehensive PubMed Search Strategy accomplishing exhaustive literature review. In this review, discuss findings experimental molecular neurobiological mechanisms underlying impact brain A thorough understanding neuroprotective potential preconditioning role resilience, among other things, may open further options prevention therapy treatment

Язык: Английский

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Molecular insights of exercise therapy in disease prevention and treatment

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Май 29, 2024

Despite substantial evidence emphasizing the pleiotropic benefits of exercise for prevention and treatment various diseases, underlying biological mechanisms have not been fully elucidated. Several attributed to signaling molecules that are released in response by different tissues such as skeletal muscle, cardiac adipose, liver tissue. These molecules, which collectively termed exerkines, form a heterogenous group bioactive substances, mediating inter-organ crosstalk well structural functional tissue adaption. Numerous scientific endeavors focused on identifying characterizing new mediators with properties. Additionally, some investigations molecular targets exerkines cellular cascades trigger adaption processes. A detailed understanding tissue-specific downstream effects is crucial harness health-related mediated improve targeted programs health disease. Herein, we review current vivo exerkine-induced signal transduction across multiple target highlight preventive therapeutic value exerkine diseases. By aspects research, provide comprehensive overview (i) underpinnings secretion, (ii) receptor-dependent receptor-independent adaption, (iii) clinical implications these disease treatment.

Язык: Английский

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Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 21, 2024

Abstract Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, cellular specificity sensitivity stress on brain epitranscriptomics its impact remain unclear. Here, we found ALKBH5, an RNA demethylase N6-methyladenosine (m6A), was increased in MDD patients’ blood models. ALKBH5 astrocytes more sensitive than neurons endothelial cells. Selective deletion astrocytes, but not cells, produced antidepressant-like behaviors. Astrocytic mPFC regulated depression-related behaviors bidirectionally. Meanwhile, modulated glutamate transporter-1 (GLT-1) m6A modification expression GLT-1 astrocytes. astrocyte-specific knockout preserved stress-induced disruption glutamatergic synaptic transmission, neuronal atrophy defective Ca 2+ activity. Moreover, enhanced with S-adenosylmethionine (SAMe) effects. Our findings indicate astrocytic depressive-like may be a therapeutic target for depression.

Язык: Английский

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Gut-derived lactic acid enhances tryptophan to 5-hydroxytryptamine in regulation of anxiety via Akkermansia muciniphila

Gut Microbes, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 9, 2025

The gut microbiota plays a pivotal role in anxiety regulation through pathways involving neurotransmitter production, immune signaling, and metabolic interactions. Among these, gut-derived serotonin (5-hydroxytryptamine, 5-HT), synthesized from tryptophan metabolism, has been identified as key mediator. However, it remains unclear whether specific microbial factors regulate metabolism to influence 5-HT production regulation. In this study, we analyzed 110 athletes undergoing closed training found that fecal lactate levels were significantly associated with indicators. We observed significant negative correlation between Akkermansia abundance athletes. Co-supplementation muciniphila (A. muciniphila) modulated by increasing enzyme TPH1 reducing IDO1, thus shifting kynurenine (Kyn) 5-HT. addition, enhanced the propionate capacity of A. muciniphila, potentially contributing reduction mice. Taken together, these findings suggest enteric collaboratively restore imbalance leading increased activity alleviating phenotypes. This study highlights intricate interplay metabolites regulation, offering potential avenues for microbiota-targeted therapeutic strategies anxiety.

Язык: Английский

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Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 22, 2025

Physical exercise effectively prevents anxiety disorders caused by environmental stress. The neural circuitry mechanism, however, remains incomplete. Here, we identified a previously unrecognized pathway originating from the primary motor cortex (M1) to medial prefrontal (mPFC) via ventromedial thalamic (VM) nuclei in male mice. Besides anatomical evidence, both ex vivo and recordings showed enhanced excitability of M1-VM inputs prelimbic (PrL) region mPFC upon 14-day treadmill on chronic restraint stress (CRS) mouse model. Further functional interrogations demonstrated that activation this circuit is necessary sufficient direct anxiolytic effect training CRS Our findings provide more insights into circuits connecting mental regions under paradigm implicate potential targets for neuromodulation treating disorders. relieves disorders, while authors show input cortex, nuclei.

Язык: Английский

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