Gut microbiota-derived metabolites as central regulators in metabolic disorders

Gut, Год журнала: 2020, Номер 70(6), С. 1174 - 1182

Опубликована: Дек. 3, 2020

Metabolic disorders represent a growing worldwide health challenge due to their dramatically increasing prevalence. The gut microbiota is crucial actor that can interact with the host by production of diverse reservoir metabolites, from exogenous dietary substrates or endogenous compounds. are associated alterations in composition and function microbiota. Specific classes microbiota-derived notably bile acids, short-chain fatty branched-chain amino trimethylamine N-oxide, tryptophan indole derivatives, have been implicated pathogenesis metabolic disorders. This review aims define key metabolites altered diseases role pathogenesis. They potential biomarkers for early diagnosis prognosis as well promising targets development novel therapeutic tools

Язык: Английский

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Molecular Probes, Chemosensors, and Nanosensors for Optical Detection of Biorelevant Molecules and Ions in Aqueous Media and Biofluids

Chemical Reviews, Год журнала: 2022, Номер 122(3), С. 3459 - 3636

Опубликована: Янв. 7, 2022

Synthetic molecular probes, chemosensors, and nanosensors used in combination with innovative assay protocols hold great potential for the development of robust, low-cost, fast-responding sensors that are applicable biofluids (urine, blood, saliva). Particularly, metabolites, neurotransmitters, drugs, inorganic ions is highly desirable due to a lack suitable biosensors. In addition, monitoring analysis metabolic signaling networks cells organisms by optical probes chemosensors becoming increasingly important biology medicine. Thus, new perspectives personalized diagnostics, theranostics, biochemical/medical research will be unlocked when standing limitations artificial binders receptors overcome. this review, we survey synthetic sensing systems have promising (future) application detection small molecules, cations, anions aqueous media biofluids. Special attention was given provide readily measurable signal through dynamic covalent chemistry, supramolecular host-guest interactions, or nanoparticles featuring plasmonic effects. This review shall also enable reader evaluate current performance terms sensitivity selectivity respect practical requirement, thereby inspiring ideas further advanced systems.

Язык: Английский

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Tryptophan Metabolism in Depression: A Narrative Review with a Focus on Serotonin and Kynurenine Pathways

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(15), С. 8493 - 8493

Опубликована: Июль 31, 2022

Depression is a common and serious disorder, characterized by symptoms like anhedonia, lack of energy, sad mood, low appetite, sleep disturbances. This disease very complex not totally elucidated, in which diverse molecular biological mechanisms are involved, such as neuroinflammation. There high need for the development new therapies gaining insights into this urgent. One important player depression amino acid tryptophan. can be metabolized two pathways context depression: serotonin kynurenine pathways. These metabolic tryptophan crucial several processes that linked with depression. Indeed, maintenance balance critical human physiological homeostasis. Thus, narrative review aims to explore metabolism (particularly pathways) depression, starting global overview about these topics ending focus on neuroinflammation, stress, microbiota, brain-derived neurotrophic factor regulation disease. Taken together, information clarify particularly

Язык: Английский

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The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(15), С. 7931 - 7931

Опубликована: Июль 25, 2021

Serotonin, also known as 5-hydroxytryptamine (5-HT), is a metabolite of tryptophan and reported to modulate the development neurogenesis enteric nervous system, gut motility, secretion, inflammation, sensation, epithelial development. Approximately 95% 5-HT in body synthesized secreted by enterochromaffin (EC) cells, most common type neuroendocrine cells gastrointestinal (GI) tract, through sensing signals from intestinal lumen circulatory system. Gut microbiota, nutrients, hormones are main factors that play vital role regulating secretion EC cells. Apart being an important neurotransmitter paracrine signaling molecule gut, gut-derived was shown exert other biological functions (in autism depression) far beyond gut. Moreover, studies conducted on regulation immune system demonstrated exerts anti-inflammatory proinflammatory effects binding different receptors under inflammatory conditions. Understanding regulatory mechanisms which participates cell metabolism physiology can provide potential therapeutic strategies for treating diseases. Herein, we review recent evidence recapitulate synthesis, regulation, biofunction improve nutrition health humans.

Язык: Английский

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Role of indoleamine 2,3-dioxygenase 1 (IDO1) and kynurenine pathway in the regulation of the aging process

Ageing Research Reviews, Год журнала: 2022, Номер 75, С. 101573 - 101573

Опубликована: Янв. 24, 2022

Indoleamine 2,3-dioxygenase 1 (IDO1) is activated in chronic inflammatory states, e.g., the aging process and age-related diseases. IDO1 enzyme catabolizes L-tryptophan (L-Trp) into kynurenine (KYN) thus stimulating KYN pathway. The depletion of L-Trp inhibits proliferation immune cells inflamed tissues it also reduces serotonin synthesis predisposing to psychiatric disorders. Interestingly, protein contains two immunoreceptor tyrosine-based inhibitory motifs (ITIM) which trigger suppressive signaling through binding PI3K p110 SHP-1 proteins. This immunosuppressive activity not dependent on catalytic IDO1. its metabolite, kynurenic acid (KYNA), are potent activators aryl hydrocarbon receptor (AhR) can enhance immunosuppression. IDO1-KYN-AhR counteracts excessive pro-inflammatory responses acute inflammation but states has many harmful effects. A low-grade associated with process, a state called inflammaging. There substantial evidence that activation pathway robustly increases process. does only suppress functions effector cells, probably promoting immunosenescence, impairs autophagy, induces cellular senescence, remodels extracellular matrix as well enhancing development osteoporosis vascular I will review function discuss an enhancer

Язык: Английский

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The Role of Tryptophan Metabolites in Neuropsychiatric Disorders

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(17), С. 9968 - 9968

Опубликована: Сен. 1, 2022

In recent decades, neuropsychiatric disorders such as major depressive disorder, schizophrenia, bipolar, etc., have become a global health concern, causing various detrimental influences on patients. Tryptophan is an important amino acid that plays indisputable role in several physiological processes, including neuronal function and immunity. Tryptophan’s metabolism process the human body occurs using different pathways, kynurenine serotonin pathways. Furthermore, other biologically active components, serotonin, melatonin, niacin, are by-products of Current evidence suggests functional imbalance synthesis metabolites causes appearance pathophysiologic mechanisms leads to diseases. This review summarizes pharmacological tryptophan its development disorders. addition, quantification following neurotransmitters precursor highlighted. Eventually, efficiency biomarkers inflammatory, protein, electrophysiological, genetic, proteomic diagnosis/treatment was discussed understand biomarker application detection/treatment

Язык: Английский

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The Role of Microbiome in Brain Development and Neurodegenerative Diseases

Molecules, Год журнала: 2022, Номер 27(11), С. 3402 - 3402

Опубликована: Май 25, 2022

Hundreds of billions commensal microorganisms live in and on our bodies, most which colonize the gut shortly after birth stay there for rest lives. In animal models, bidirectional communications between central nervous system microbiota (Gut-Brain Axis) have been extensively studied, it is clear that changes composition play a vital role pathogenesis various neurodevelopmental neurodegenerative disorders, such as Autism Spectrum Disorder, Alzheimer's disease, Parkinson's Multiple Sclerosis, Amyotrophic Lateral anxiety, stress, so on. The makeup microbiome impacted by variety factors, genetics, health status, method delivery, environment, nutrition, exercise, present understanding its metabolites preservation brain functioning development aforementioned neurological illnesses summarized this review article. Furthermore, we discuss current breakthroughs use probiotics, prebiotics, synbiotics to address illnesses. Moreover, also discussed boron-based diet memory, boron relation, anti-inflammatory agents, diseases. addition, coming years, reagents will significant improve dysbiosis open new areas researchers.

Язык: Английский

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Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

Cells, Год журнала: 2024, Номер 13(5), С. 423 - 423

Опубликована: Фев. 28, 2024

The involvement of central and peripheral inflammation in the pathogenesis prognosis major depressive disorder (MDD) has been demonstrated. increase pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, IL-18, TNF-α) individuals with depression may elicit neuroinflammatory processes inflammation, mechanisms that, turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation dysbiosis induce alterations tryptophan metabolism, culminating decreased serotonin synthesis, impairments neuroplasticity-related mechanisms, glutamate-mediated excitotoxicity. This review aims highlight inflammatory (neuroinflammation, dysbiosis) involved pathophysiology MDD explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines evidence have indicated that addition antidepressants, physical exercise, probiotics, nutraceuticals (agmatine, ascorbic acid, vitamin D) possess effects their antidepressant properties. Further studies are necessary benefits these alternative therapies MDD.

Язык: Английский

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Microbiota–gut–brain axis mechanisms in the complex network of bipolar disorders: potential clinical implications and translational opportunities

Molecular Psychiatry, Год журнала: 2023, Номер 28(7), С. 2645 - 2673

Опубликована: Янв. 27, 2023

Abstract Bipolar disorders (BD) represent a severe leading disabling mental condition worldwide characterized by episodic and often progressive mood fluctuations with manic depressive stages. The biological mechanisms underlying the pathophysiology of BD remain incompletely understood, but it seems that there is complex picture genetic environmental factors implicated. Nowadays, gut microbiota in spotlight new research related to this kind psychiatric disorder, as can be consistently several pathophysiological events observed BD. In context so-called microbiota–gut–brain (MGB) axis, shown have strong influence on host neuromodulation endocrine functions (i.e., controlling synthesis neurotransmitters like serotonin or mediating activation hypothalamic–pituitary–adrenal axis), well modulation immune responses, critically regulating intestinal, systemic brain inflammation (neuroinflammation). present review aims elucidate derived from MGB axis disruption possible therapeutic approaches mainly focusing network Understanding its bidirectional communication other systems shed light discovery therapies for improving clinical management these patients. Besides, effect drugs currently used patients, together therapeutical targeting ecosystem (dietary patterns, probiotics, prebiotics, novelties) will also contemplated.

Язык: Английский

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The role of the indoles in microbiota-gut-brain axis and potential therapeutic targets: A focus on human neurological and neuropsychiatric diseases

Neuropharmacology, Год журнала: 2023, Номер 239, С. 109690 - 109690

Опубликована: Авг. 22, 2023

Язык: Английский

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