Microbiome modifications by steroids during viral exacerbation of asthma and in healthy mice

AJP Lung Cellular and Molecular Physiology, Journal Year: 2024, Volume and Issue: 327(5), P. L646 - L660

Published: Aug. 19, 2024

In the present studies, assessment of how viral exacerbation asthmatic responses with and without pulmonary steroid treatment alters microbiome in conjunction immune presents striking data. The overall findings identify that although allergic animals diminished severity respiratory syncytial virus (RSV)-induced airway function mucus hypersecretion, there were local increases IL-17 expression. Analysis lung gut suggested are differences RSV further altered by fluticasone (FLUT) treatment. Using metagenomic inference software, PICRUSt2, we able to predict metabolite profile produced changed was significantly different multiple metabolic pathways associated specific treatments or FLUT. Importantly, measuring plasma metabolites an unbiased manner, our data indicate significant changes chronic allergen exposure, exacerbation, FLUT reflective disease addition, appeared have contributions from both host microbial pathways. To understand if steroids on their own along infection, naïve treated before infection. infection demonstrated enhanced corresponded related PICRUSt2 analysis. Altogether, these set foundation for identifying important correlations severe exacerbated relationship metabolome a potential early life influence subsequent viral-induced disease.

Language: Английский

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Plasma and Visceral Organ Kynurenine Metabolites Correlate in the Multiple Sclerosis Cuprizone Animal Model

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 976 - 976

Published: Jan. 24, 2025

The cuprizone (CPZ) model of multiple sclerosis (MS) is excellent for studying the molecular differences behind damage caused by poisoning. Metabolic in kynurenine pathway (KP) tryptophan (TRP) degradation are observed both MS and a CPZ mouse model. Our goal was to analyze kynurenine, serotonin, indole pathways TRP on periphery, neurodegenerative processes inflammation. In our study, mice were fed with 0.2% toxin 5 weeks. We examined metabolites three breakdown urine, plasma, relevant visceral organs bioanalytical measurements. analyses, we found significant increase plasma TRP, 5-hydroxytryptophan (5-HTP), indole-3-acetic acid (IAA) levels, while decrease concentrations 3-hydroxy-L-kynurenine (3-HK), xanthurenic (XA), kynurenic (KYNA), quinaldic toxin-treated group found. A marked levels 3-HK, XA, KYNA, acid, indole-3-lactic also end Furthermore, noticed urinary XA metabolites, an serotonin 5-hydroxyindoleacetic noticed. treatment resulted elevated tryptamine indoxyl sulfate reduced IAA concentration. Moreover, para-cresyl concentration increased treated group. present showed main metabolic confirmed relationship correlation between content tissues organs. emphasized suppression KP activity particular regard involvement microbiome pathway. Consequently, this first study detail distribution periphery.

Language: Английский

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CF airway epithelia display exaggerated host defense responses and prolonged cilia loss during RSV infection

Journal of Cystic Fibrosis, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Physiologic relevance of the transpulmonary metabolome in connective tissue disease–associated pulmonary vascular disease

JCI Insight, Journal Year: 2025, Volume and Issue: 10(9)

Published: May 7, 2025

Pathologic implications of dysregulated pulmonary vascular metabolism to arterial hypertension (PAH) are increasingly recognized, but their clinical applications have been limited. We hypothesized that metabolite quantification across the bed in connective tissue disease-associated (CTD-associated) PAH would identify transpulmonary gradients pathobiologically relevant metabolites, an exercise stage-specific manner. Sixty-three CTD patients with established or suspected underwent right heart catheterization. Using mass spectrometry-based metabolomics, metabolites were quantified plasma samples simultaneously collected from and radial arteries at baseline during resistance-free wheeling, peak exercise, recovery. identified uptake excretion bed, unique distinct single site analysis. demonstrated physiological relevance previously shown promote disease animal models end-stage human lung tissues, including acylcarnitines, glycolytic intermediates, tryptophan catabolites. Notably, handling was stage specific. Transpulmonary correlated hemodynamic endpoints largely free-wheeling. Glycolytic intermediates physiologic significance net lactate those more advanced disease. Contribution CTD-PAH pathogenesis therapeutic candidacy modulation must be considered context stress.

Language: Английский

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Antibiotic‐Induced Dysbiosis of the Gut Microbiota Shifts Host Tryptophan Metabolism and Increases the Susceptibility of Mice to Pulmonary Infection With Pseudomonas aeruginosa

Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

ABSTRACT Pseudomonas aeruginosa is an opportunistic bacterium that mainly infects those who have previously been treated with antibiotics. We hypothesised antibiotic treatment disrupts tryptophan metabolism, leading to increased susceptibility P. infection. Our results showed mice receiving antibiotics exhibited intestinal dysbiosis alterations in host a higher mortality rate and bacterial load compared eubiotic mice. In the lungs of dysbiotic mice, there was increase IDO1 (Indoleamine 2,3‐dioxygenase 1) activity accumulation kynurenine after infection, −/− were resistant infection induction dysbiosis. Importantly, led expression activation AHR (Aryl Hydrocarbon Receptor) IDO1‐dependent manner. Blocking resulted lower load. data by associated decreased phagocytosis macrophages neutrophils. conclusion, our indicate resulting from prolonged antimicrobial alters IDO1–AHR axis increasing Furthermore, these suggest or are potential targets for prevention infections patients undergoing therapy.

Language: Английский

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Gut microbiota and exercise-induced fatigue: unraveling the connections

Food Science of Animal Products, Journal Year: 2024, Volume and Issue: 2(2), P. 9240061 - 9240061

Published: June 1, 2024

Exercise-induced fatigue (EF) refers to the physiological processes that impair body's ability maintain desired levels of functioning and sustain predetermined exercise intensity. It encompasses peripheral discomfort (e.g., muscle soreness, weakness) central exhaustion, characterized by emotional sleep disturbances. The detrimental effects EF significantly impact human productivity lifestyle. Given crosstalk between gut microbiota metabolism in exercise, there is a growing interest investigating role elucidating mechanisms underlying EF. Furthermore, exploring dietary interventions as novel approach alleviate has gained attention. Our work comprehensively synthesizes alterations community structure function caused EF, evaluates existing evidence on potential probiotics regulation This review aims enhance our understanding correlation microbiome explores use mitigating

Language: Английский

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Kynurenines and Inflammation: A Remarkable Axis for Multiple Sclerosis Treatment

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(8), P. 983 - 983

Published: July 25, 2024

Multiple sclerosis (MS) is a chronic inflammatory autoimmune neurological disease characterized by the recurrent appearance of demyelinating lesions and progressive disability. Currently, there are multiple disease-modifying treatments, however, significant need to develop new therapeutic targets, especially for forms disease. This review article provides an overview most recent studies aimed at understanding processes that activated in response accumulation kynurenine pathway (KP) metabolites, which exacerbate imbalance between immune system cells (e.g., Th1, Th2, T reg) promote release pro-inflammatory interleukins modulate different mechanisms: membrane-receptors function; nuclear factors expression; cellular signals. Together, these alterations trigger cell death mechanisms brain neuron loss axon demyelination. hypothesis could represent remarkable approach therapies MS. Here, we also provide perspective on repositioning some already approved drugs involved other signaling pathways, strategies MS treatment.

Language: Английский

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The Connection Between the Oral Microbiota and the Kynurenine Pathway: Insights into Oral and Certain Systemic Disorders

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(11), P. 12641 - 12657

Published: Nov. 7, 2024

The oral microbiome, comprising bacteria, fungi, viruses, and protozoa, is essential for maintaining both systemic health. This complex ecosystem includes over 700 bacterial species, such as

Language: Английский

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