The tryptophan metabolic pathway of the microbiome and host cells in health and disease

International Immunology, Год журнала: 2024, Номер unknown

Опубликована: Июнь 13, 2024

Abstract The intricate and dynamic tryptophan (Trp) metabolic pathway in both the microbiome host cells highlights its profound implications for health disease. This involves complex interactions between cellular bacteria processes, producing bioactive compounds such as 5-hydroxytryptamine (5-HT) kynurenine derivatives. Immune responses to Trp metabolites through specific receptors have been explored, highlighting role of aryl hydrocarbon receptor inflammation modulation. Dysregulation this is implicated various diseases, Alzheimer’s Parkinson’s mood disorders, neuronal autoimmune diseases multiple sclerosis (MS), cancer. In article, we describe impact 5-HT, Trp, indole, on Furthermore, review microbiome-derived that affect immune contribute maintaining homeostasis, especially an experimental encephalitis model MS.

Язык: Английский

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The gut–organ axis: Clinical aspects and immune mechanisms

Allergology International, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

The gut-brain axis exemplifies the bidirectional connection between intestines and brain, as evidenced by impact of severe stress on gastrointestinal symptoms including abdominal pain diarrhea, conversely, influence discomfort mood. Clinical observations support notion connection, an increased prevalence inflammatory bowel disease (IBD) in patients with depression anxiety, well association changes gut microbiota neurological disorders such multiple sclerosis, Parkinson's disease, stroke Alzheimer's disease. brain communicate via complex mechanisms involving cytokines, immune cells, autonomic nerves, microbiota, which contribute to pathogenesis certain diseases. Two primary pathways mediate information exchange intestinal tract brain: signal transduction through bloodstream factors, bacterial metabolites neural pathways, neurotransmitters cytokines within nervous system interaction nerve cells beyond. In recent years, basic pathophysiology have been gradually elucidated. Beyond interaction, emerging evidence suggests extends other organs, liver lungs, intricate inter-organ communication pathways. An increasing number reports this clinical cross-organ interactions underscore potential for better understanding novel therapeutic strategies targeting inter-organs networks. Further clarification multiorgans premises transformative insights into strategies.

Язык: Английский

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Exploring effects of gut microbiota on tertiary lymphoid structure formation for tumor immunotherapy

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Март 7, 2025

Anti-tumor immunity, including innate and adaptive immunity is critical in inhibiting tumorigenesis development of tumor. The needs specific lymph organs such as tertiary lymphoid structures (TLSs), which are highly correlated with improved survival outcomes many cancers. In recent years, increasing attention on the TLS tumor microenvironment, TLSs have emerged a novel target for anti-tumor therapy. Excitingly, studies shown contribution to immune responses. However, it unclear how form more effectively defense against through formation. Recent that inflammation plays role Interestingly, also found gut microbiota can regulate occurrence inflammation. Therefore, we here summarize potential effects microbiota- mediated or immunosuppression formation environments. Meanwhile, this review explores manipulate mature regulating microbiota/metabolites associated signal pathways potentially lead next-generation cancer immunotherapy.

Язык: Английский

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The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 9082 - 9082

Опубликована: Авг. 21, 2024

Kynurenic acid (KYNA) is an antioxidant degradation product of tryptophan that has been shown to have a variety cytoprotective, neuroprotective and neuronal signalling properties. However, mammalian transporters receptors display micromolar binding constants; these are consistent with its typically tissue concentrations but far above serum/plasma concentration (normally tens nanomolar), suggesting large gaps in our knowledge transport mechanisms action, the main influx characterized date equilibrative, not concentrative. In addition, it substrate known anion efflux pump (ABCC4), whose vivo activity largely unknown. Exogeneous addition L-tryptophan or L-kynurenine leads production KYNA also many other co-metabolites (including some such as 3-hydroxy-L-kynurenine quinolinic may be toxic). With exception chestnut honey, exists at relatively low levels natural foodstuffs. bioavailability reasonable, terminal element irreversible reaction most pathways, might added exogenously without disturbing upstream metabolism significantly. Many examples, which we review, show valuable bioactivity. Given above, review potential utility nutraceutical, finding significantly worthy further study development.

Язык: Английский

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GPR35 acts a dual role and therapeutic target in inflammation

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 16, 2023

GPR35 is a G protein-coupled receptor with notable involvement in modulating inflammatory responses. Although the precise role of inflammation not yet fully understood, studies have suggested that it may both pro- and anti-inflammatory effects depending on specific cellular environment. Some shown activation can stimulate production pro-inflammatory cytokines facilitate movement immune cells towards tissues or infected areas. Conversely, other investigations possess properties gastrointestinal tract, liver certain by curbing generation mediators endorsing differentiation regulatory T cells. The intricate underscores requirement for more in-depth research to thoroughly comprehend its functional mechanisms potential significance as therapeutic target diseases. purpose this review concurrently investigate roles GPR35, thus illuminating facets complex issue.

Язык: Английский

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The toxic effects of tetracycline exposure on the physiological homeostasis of the gut-liver axis in grouper

Environmental Research, Год журнала: 2024, Номер 258, С. 119402 - 119402

Опубликована: Июнь 12, 2024

Язык: Английский

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Importance of Gut Microbiota Dysbiosis and Circadian Disruption–Associated Biomarkers in Emergence of Alzheimer’s Disease

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Язык: Английский

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Impact of Sleep Deprivation on Colon Cancer: Unraveling the KynA-P4HA2-HIF-1α Axis in Tumor Lipid Metabolism and Metastasis

Molecular Metabolism, Год журнала: 2025, Номер 93, С. 102109 - 102109

Опубликована: Фев. 6, 2025

There is growing evidence that sleep deprivation promotes cancer progression. In addition, colon patients often experience due to factors such as pain and side effects of treatment. The occurrence liver metastases an important factor in the mortality patients. However, relationship between from has not been elucidated. A metastasis model was constructed evaluate effect on cancer. Subsequently, mice feces were collected for untargeted metabolomics screen identify key mediator, Kynurenic acid (KynA). Furthermore, HILPDA screened by transcriptomics, its potential mechanism explored through ChIP, co-IP, ubiquitination experiments, phenotyping etc. RESULTS: Sleep Functionally, aggravates lipid accumulation decreases production microbiota metabolite KynA. contrast, KynA inhibited progression vitro. vivo, supplementation reversed promoting Mechanistically, downregulates expression P4HA2 promote degradation HIF-1α, which leads a decrease transcription HILPDA, ultimately increase lipolysis cells. Our findings reveal impairs intracellular KynA, leading droplets This process metastasis. suggests promising strategy

Язык: Английский

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Metabolism of Tryptophan, Glutamine, and Asparagine in Cancer Immunotherapy—Synergism or Mechanism of Resistance?

Metabolites, Год журнала: 2025, Номер 15(3), С. 144 - 144

Опубликована: Фев. 21, 2025

Amino acids are crucial components of proteins, key molecules in cellular physiology and homeostasis. However, they also involved a variety other mechanisms, such as energy homeostasis, nitrogen exchange, further synthesis bioactive compounds, production nucleotides, or activation signaling pathways. Moreover, amino their metabolites have immunoregulatory properties, significantly affecting the behavior immune cells. Immunotherapy is one oncological treatment methods that improves cytotoxic properties one’s own system. Thus, enzymes catalyzing acid metabolism, together with themselves, can affect antitumor responses to immunotherapy. In this review, we will discuss involvement tryptophan, glutamine, asparagine metabolism cells targeted by immunotherapy summarize results most recent investigations on impact

Язык: Английский

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Activation of GPR35 by kynurenic acid inhibits IL-1β secretion in macrophages during CR-hvKP-induced pneumonia

International Immunopharmacology, Год журнала: 2025, Номер 153, С. 114416 - 114416

Опубликована: Март 18, 2025

Carbapenemase-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is a common pathogen that can cause severe pneumonia. The innate immune response, especially the response of macrophages, plays crucial role in host's defense against bacterial infections. Glycolysis implicated modulation functions macrophages. Here, we provide evidence supporting GPR35 decreasing glycolysis and reducing secretion IL-1β macrophages by inhibiting transcription HK2 during K. pneumoniae-induced Mice with knock-out exhibit higher mortality increased lung burdens. Mechanistically, activation kynurenic acid inhibits caspase-1 cleavage reduces specifically suppressing NLRP3 inflammasome. These findings underscore regulating inflammation pneumonia suggest potential therapeutic target for clinical treatment.

Язык: Английский

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