Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives

Aging and Disease, Journal Year: 2022, Volume and Issue: 13(4), P. 1106 - 1106

Published: Jan. 1, 2022

Gut microbiota, a collection of microorganisms that live within gastrointestinal tract, provides crucial signaling metabolites for the physiological hosts. In healthy state, gut microbiota are helpful maintaining basic functions hosts, whereas disturbed production these can lead to numerous diseases such as metabolic diseases, cardiovascular neurodegenerative and cancer. Although there many reviews about specific mechanisms on is no comprehensive summarization metabolites. this Opinion, we discuss knowledge including types their ways acting targets. addition, summarize pathologic in health shaping composition nutrition. This paper be understanding roles thus provide guidance developing suitable therapeutic strategies combat microbial-driven improve health.

Language: Английский

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Molecular pathways of major depressive disorder converge on the synapse

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(1), P. 284 - 297

Published: Oct. 6, 2022

Abstract Major depressive disorder (MDD) is a psychiatric disease of still poorly understood molecular etiology. Extensive studies at different levels point to high complexity numerous interrelated pathways as the underpinnings depression. systems under consideration include monoamines, stress, neurotrophins and neurogenesis, excitatory inhibitory neurotransmission, mitochondrial dysfunction, (epi)genetics, inflammation, opioid system, myelination, gut-brain axis, among others. This review aims illustrating how these multiple signaling may interact provide more comprehensive view MDD’s neurobiology. In particular, considering pattern synaptic activity closest physical representation mood, emotion, conscience we can conceptualize, each pathway or system will be scrutinized for links neurotransmission. Models neurobiology MDD discussed well future actions improve understanding treatment options.

Language: Английский

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

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(15), P. 7931 - 7931

Published: July 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.

Language: Английский

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Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: June 19, 2023

Cognitive function in humans depends on the complex and interplay between multiple body systems, including hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells has a genetic potential that exceeds of genome, plays crucial role this interplay. microbiota-gut-brain (MGB) axis is bidirectional signalling pathway operates through neural, endocrine, immune, metabolic pathways. One major neuroendocrine systems responding to stress HPA produces glucocorticoids such as cortisol corticosterone rodents. Appropriate concentrations are essential for normal neurodevelopment function, well cognitive processes learning memory, studies have shown microbes modulate throughout life. Stress can significantly impact MGB via other Animal research advanced our understanding these mechanisms pathways, leading paradigm shift conceptual thinking about influence microbiota health disease. Preclinical trials currently underway determine how animal models translate humans. In review article, we summarize current knowledge relationship axis, cognition, provide an overview main findings conclusions broad field.

Language: Английский

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The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases

Biomolecules, Journal Year: 2022, Volume and Issue: 12(7), P. 998 - 998

Published: July 18, 2022

Emerging evidence suggests that neuroinflammation is involved in both depression and neurodegenerative diseases. The kynurenine pathway, generating metabolites which may play a role pathogenesis, one of several competing pathways tryptophan metabolism. present article narrative review metabolism, neuroinflammation, depression, neurodegeneration. A disturbed metabolism with increased activity the pathway production quinolinic acid result deficiencies derived neurotransmitters. Quinolinic an N-methyl-D-aspartate receptor agonist, raised levels CSF, together inflammatory cytokines, have been reported mood disorders. Increased has also observed diseases, including Parkinson's disease, Alzheimer's amyotrophic lateral sclerosis, HIV-related cognitive decline. Oxidative stress connection indole-dioxygenase (IDO) formation contribute to responses cytokines. occur at expense kynurenic neuroprotective picolinic acid. While awaiting ongoing research on potential pharmacological interventions adequate protein intake appropriate amounts antioxidants offer protection against oxidative provide balanced set physiological ligands.

Language: Английский

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Gut Microbiome–Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(10), P. 1717 - 1763

Published: May 8, 2023

Gut microbiota includes a vast collection of microorganisms residing within the gastrointestinal tract. It is broadly recognized that gut and brain are in constant bidirectional communication, which its metabolic production major component, form so-called microbiome–brain axis. Disturbances homeostasis caused by imbalance their functional composition activities, known as dysbiosis, cause dysregulation these pathways trigger changes blood–brain barrier permeability, thereby causing pathological malfunctions, including neurological disorders. In turn, can affect structure function through autonomic nervous system regulating motility, intestinal transit secretion, permeability. Here, we examine data from CAS Content Collection, largest published scientific information, analyze publication landscape recent research. We review advances knowledge related to human microbiome, complexity functionality, communication with central system, effect axis on mental health. discuss correlations between various diseases, specifically also explore metabolites regard impact associated diseases. Finally, assess clinical applications gut-microbiota-related substances development pipelines. hope this serve useful resource understanding current emerging field an effort further solving remaining challenges fulfilling potential.

Language: 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, Journal Year: 2022, Volume and Issue: 75, P. 101573 - 101573

Published: Jan. 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

Language: Английский

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

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 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.

Language: Английский

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The Role of Tryptophan Metabolites in Neuropsychiatric Disorders

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 9968 - 9968

Published: Sept. 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

Language: Английский

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Microbiota-derived indoles alleviate intestinal inflammation and modulate microbiome by microbial cross-feeding

Microbiome, Journal Year: 2024, Volume and Issue: 12(1)

Published: March 19, 2024

Abstract Background The host–microbiota interaction plays a crucial role in maintaining homeostasis and disease susceptibility, microbial tryptophan metabolites are potent modulators of host physiology. However, whether how these mediate interactions, particularly terms inter-microbial communication, remains unclear. Results Here, we have demonstrated that indole-3-lactic acid (ILA) is key molecule produced by Lactobacillus protecting against intestinal inflammation correcting dysbiosis. Specifically, metabolizes into ILA, thereby augmenting the expression bacterial enzymes implicated metabolism, leading to synthesis other indole derivatives including indole-3-propionic (IPA) indole-3-acetic (IAA). Notably, IPA, IAA possess ability mitigate modulate gut microbiota both DSS-induced IL-10 −/− spontaneous colitis models. ILA increases abundance tryptophan-metabolizing bacteria (e.g., Clostridium ), as well mRNA acyl-CoA dehydrogenase indolelactate vivo vitro, resulting an augmented production IPA IAA. Furthermore, mutant strain fails protect producing derivatives. ILA-mediated cross-feeding was microbiota-dependent specifically enhanced under conditions dysbiosis induced Citrobacter rodentium or DSS, but not disruption with antibiotics. Conclusion Taken together, highlight mechanisms which microbiome-host crosstalk cooperatively control homoeostasis through microbiota-derived indoles mediating communication. These findings may contribute development targeted “postbiotic” potential interventions for treatment prevention dysbiosis-driven diseases.

Language: Английский

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