Gut microbiota-derived metabolites and chronic inflammatory diseases

Exploration of Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

The gut microbiota, a complex ecosystem of microorganisms, plays an essential role in maintaining immune and metabolic homeostasis. Disruption this microbial balance, known as dysbiosis, has been increasingly implicated the pathogenesis chronic inflammatory conditions, including cardiovascular, gastrointestinal, autoimmune diseases, well disorders such diabetes obesity. A crucial mechanism through which microbiota exerts its effects on host physiology is via production bioactive metabolites. These metabolites, short-chain fatty acids, bile tryptophan derivatives, are key modulating responses regulating functions. Dysbiosis disrupts function these thereby contributing to dysregulation, inflammation, disease progression. This review examines microbiota-derived metabolites with focus their immunomodulatory effects. deeper understanding mechanisms may open way for novel therapeutic strategies aimed at restoring homeostasis mitigating global burden diseases.

Language: Английский

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A glucan from Ganoderma lucidum: structural characterization and the anti-inflammatory effect on Parkinson's Disease via regulating dysfunctions of intestinal microecology and inhibiting TLR4/MyD88/NF-κB signaling pathway

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: 343, P. 119446 - 119446

Published: Feb. 4, 2025

Language: Английский

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Non-targeted metabolomic profile of Leuconostoc mesenteroides-fermented milk reveals differentially expressed metabolites associated with electro-fermentation

Microbial Cell Factories, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 22, 2025

Leuconostoc mesenteroides (L. mesenteroides) has known as an electrogenic probiotic bacterium. However, metabolites related to electro-fermentation in ferments of L. are not unveiled. Electrogenic fermentatively metabolized bovine milk dense with homogeneous particle-size distribution. A non-targeted metabolomics approach was performed on non-fermented and mesenteroides-fermented milk. total 917 were identified quantified by ultra-high performance liquid chromatography (UHPLC)-tandem mass spectrometry (MS-MS). Thirteen prokaryotic metabolic pathways associated differentially expressed (DEMs) revealed through Koto Encyclopedia Genes Genomes (KEGG) enrichment analysis. Anthranilic acid (AA) 3-hydroxyanthranilin (3-HAA), potentially electron donors, quinolinic acid, donor precursor, the tryptophan kynurenine pathway significantly increased fermented Histidine, arginine, riboflavin involved bacterial survival or bioelectricity production elevated after fermentation. Results indicate that can mediate transform a new nutritional source which is rich donors reportedly acting antioxidants.

Language: Английский

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

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9082 - 9082

Published: Aug. 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.

Language: Английский

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Tryptophan metabolism-related gene CYP1B1 serves as a shared biomarker for both Parkinson’s disease and insomnia

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 8, 2025

Parkinson's disease (PD) and insomnia are prevalent neurological disorders, with emerging evidence implicating tryptophan (TRP) metabolism in their pathogenesis. However, the precise mechanisms by which TRP contributes to these conditions remain insufficiently elucidated. This study explores shared metabolism-related genes (TMRGs) molecular underlying PD insomnia, aiming provide insights into We analyzed datasets for (GSE100054) (GSE208668) obtained from Gene Expression Omnibus (GEO) database. TMRGs were Molecular Signatures Database (MSigDB) Genecards Tryptophan differentially expressed (TM-DEGs) identified intersecting (DEGs) datasets. Through Protein–Protein Interaction (PPI) network analysis, Support Vector Machine-Recursive Feature Elimination (SVM-RFE) , Extreme Gradient Boosting (XGBoost) machine learning, we Cytochrome P4501B1 (CYP1B1) Electron Transfer Flavoprotein Alpha (ETFA) as key hub genes. Subsequently, employed CIBERSORT single-sample gene set enrichment analysis (ssGSEA) further investigate association between peripheral immune activation inflammatory response. Additionally, interaction, Drug-mRNA, Transcription Factor (TF)-mRNA, competing endogenous RNA (ceRNA) networks centered on constructed explore regulatory potential drug interactions. Finally, validation through bioinformatics animal experiments CYP1B1 a promising biomarker associated both insomnia.

Language: Английский

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Tryptophan metabolites profile predict remission with dietary therapy in pediatric Crohn’s disease

Therapeutic Advances in Gastroenterology, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 1, 2025

Background: Crohn’s disease (CD) exclusion diet combined with partial enteral nutrition (CDED + PEN) or exclusive (EEN) is effective in inducing remission mild-to-moderate pediatric CD. Although CDED PEN better tolerated and has higher compliance compared to EEN, a subset of patients does not achieve remission. Diet-induced shown be positively associated specific changes tryptophan-metabolites. Objectives: To investigate whether the abundance baseline fecal tryptophan-metabolites predicts dietary therapy outcomes Design: Diagnostic accuracy study secondary analysis previously conducted Randomized Controlled Trial (RCT). Methods: Twenty-six from performed RCT CD were included. The classified as having clinical (R) ( n = 19 total; 10 EEN 9) No-Remission (NR) 7 3 4) following 6 weeks therapy, based on Pediatric Disease Activity Index score (⩽10 remission). We targeted quantitative 21 t 0) samples both groups, utilizing liquid chromatography coupled quadrupole mass spectrometry. Receiver operator characteristic curve (ROC) random forest (RFA) used assess predictive power for at baseline. Ratios different downstream tryptophan pathways. Results: Baseline kynurenine level was significantly NR R p 0.02) 0.04). ROC highlighted robust (area under (AUC 0.97)) 0.88)-induced RFA corroborated these observations. ratio serotonin/kynurenine strongest predictor PEN-induced 1). 5-hydroxytryptophan/kynurenine 0.88) predicted EEN-induced By combining data 0.91) ratios quinolinic acid/kynurenine 0.93) kynurenine/indole-3-acetic acid demonstrated strong performance therapy-induced Conclusion: metabolites have potential serve biomarker Some metabolite showed most promising capabilities. If confirmed validation studies, markers may able provide much-needed guidance personalize intervention within management registration: NCT01728870.

Language: Английский

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Unraveling the effects of allelopathic algicide on Microcystis population: microcystin pollution risk assessment and proteomic-metabolomic insights into the sensitivity of toxic and non-toxic strains

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: unknown, P. 138671 - 138671

Published: May 1, 2025

Language: Английский

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Indole-3-Carboxaldehyde Alleviates LPS-Induced Intestinal Inflammation by Inhibiting ROS Production and NLRP3 Inflammasome Activation

Antioxidants, Journal Year: 2024, Volume and Issue: 13(9), P. 1107 - 1107

Published: Sept. 13, 2024

Indole-3-carboxaldehyde (IAld) is a tryptophan (Trp) metabolite derived from gut microbiota, which has potential protective effect on intestinal inflammatory diseases. Abnormal activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome an important cause inflammation. However, the and mechanism IAld NLRP3 remain unclear. Here, we found that inhibited in epithelial cells, effectively prevented barrier injury caused by lipopolysaccharide (LPS) stimulation. Mechanistically, demonstrated activated aryl hydrocarbon (AhR), subsequently reactive oxygen species (ROS) production, maintained mitochondrial membrane potential, blocked NF-κB/NLRP3 pathway cells. Also, AhR-specific inhibitor CH-223191 IAld-induced inhibition repairment. In addition, vivo results showed pro-inflammatory mediator production damage LPS-induced mice, related to AhR inhibition. Collectively, our study unveiled effective endogenous antioxidant suggested as treatment target for NLRP3-induced

Language: Английский

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Caveolae with serotonin and NMDA receptors as promising targets for the treatment of Alzheimer’s disease

International Journal of Physiology Pathophysiology and Pharmacology, Journal Year: 2024, Volume and Issue: 16(5), P. 96 - 110

Published: Jan. 1, 2024

Alzheimer's disease is the most general type of cognitive impairments. Until recently, strategies that prevent its clinical progression have remained more elusive. Consequently, research direction should be for finding effective neuroprotective agents. It has been suggested oxidative stress, mitochondrial injury, and inflammation level might lead to brain cell death in many neurological disorders. Therefore, several autophagy-targeted bioactive compounds may promising candidate therapeutics prevention damage. Interestingly, some risk genes are expressed within cells, which linked cholesterol metabolism, lipid transport, endocytosis, exocytosis and/or caveolae formation, suggesting a fruitful therapeutic target improve This review would highlight latest advances technologies treatment disease. In particular, paradigm serotonin N-methyl-d-aspartate (NMDA) receptors agonist/antagonist structure possibly impairment. cellular membrane biophysics our understanding pathology dysfunction associated with Here, this purpose therapy open potential move care toward disease-modifying certain benefits patients.

Language: Английский

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