Inflammatory factors and risk of lung adenocarcinoma: a Mendelian randomization study mediated by blood metabolites

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 27, 2024

Background Lung adenocarcinoma (LUAD) is the most common type of lung cancer, and its pathogenesis remains not fully elucidated. Inflammation metabolic dysregulation are considered to play crucial roles in LUAD development, but their causal relationships specific mechanisms remain unclear. Methods This study employed a two-sample Mendelian randomization (MR) approach systematically evaluate associations between 91 circulating inflammatory factors, 1,400 serum metabolites, LUAD. We utilized genome-wide association studies (GWAS) data from FinnGen biobank GWAS metabolites factors catalog conduct MR analyses. For identified key we further used mediator investigate mediating effects influence IL-17A on explored potential through protein-protein interaction functional enrichment Results The analyses revealed that (OR 0.78, 95%CI 0.62-0.99) was negatively associated with LUAD, while 71 were significantly Among them, ferulic acid 4-sulfate may role suppression by 0.87, 0.78-0.97). exert anti-LUAD extensive interactions genes related metabolism (such as SULT1A1, CYP1A1, etc.), inhibiting oxidative stress responses, well downstream tumor-related pathways MAPK, NF-κB, etc.). Conclusion discovered IL-17A, multiple occurrence, revealing pathogenesis. Our findings provide new evidence-based medical support for early predictive risk assessment biomarkers offering important clues subsequent mechanistic precision medicine applications.

Language: Английский

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Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization study

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 23, 2025

Background This study explored the causal connection among plasma lipidome, nonalcoholic fatty liver disease (NAFLD), and potential metabolome mediators through Mendelian randomization (MR). Methods We obtained summary statistics for 179 lipidome traits ( N = 7,174), 1,400 8,299), one NAFLD trait from publicly available genome-wide association studies. A two-sample MR analysis was conducted to infer causality. Additionally, multiple sensitivity analyses were assess heterogeneity, horizontal pleiotropy, robustness of findings. MetaboAnalyst 6.0 used pathway identified lipids metabolites. Furthermore, we mediation whether effect on mediated by metabolome. Results The predicted a genetically determined relationship between lipidomes NAFLD. No compelling proof found that influenced risk five mentioned earlier. Based established relationships metabolites, eight metabolic pathways are closely associated with Our revealed six relationships, indicating specific pleiotropy in analysis. Conclusions In summary, our lipidomes, metabolomes, Certainly, impact is not limited need further investigate into other possible mediators. These factors may become new biomarkers contributing its prevention, diagnosis, treatment.

Language: Английский

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Differential effects of high-fat diet on salivary and gut microbiota

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 24, 2025

Microorganisms contribute to the pathogenesis of obesity, while more studies focus on gut microbiome. However, relationship between oral microbiota and obesity has yet be elucidated. This study was designed investigate similarities differences in effects a high-fat diet salivary through mouse experiments, exploring hypothesis that microbial mechanisms may obesity. An obese model established male C57BL/6J mice by feeding diet, confirmed body weight records blood glucose tests. evaluated physiological mice. 16S rRNA sequencing technology used analyze changes microbiota, gas chromatography-mass spectrometry employed evaluate 17 short-chain medium-chain fatty acids quantitatively. The distribution different (HFD) normal chow (NCD) groups. At genus level Streptococcus Escherichia were highly abundant HFD group. Rodentibacter Turicibacter NCD Regarding microbiome, diversity are significant than those microbiota. group had significantly higher abundance Kineothrix, Cryptobacteroides, lower CAG-485. Nine genera consistent alterations among which Akkermansia, Lactobacillus, Intestinimonas correlated with indicators, Muribaculum increased decanoic acid levels dysregulated nine associated upregulation certain metabolic pathways group, including pentose phosphate, bacterial invasion epithelial cells, steroid biosynthesis pathways. There Certain oral-gut axis altered consistently affect involving inflammation.

Language: Английский

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Causal Correlations Between Plasma Metabolites, Inflammatory Proteins, and Chronic Obstructive Pulmonary Disease: A Mendelian Randomization and Bioinformatics-Based Investigation

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 4057 - 4073

Published: March 1, 2025

An increasing number of studies have demonstrated a strong correlation between metabolism, inflammation, and chronic obstructive pulmonary disease (COPD). However, it remains unclear if there is causal relationship these factors. This study employed the Mendelian randomization (MR) approach to investigate associations factors explore mediating roles key inflammatory proteins. MR was used assess plasma metabolites, proteins, COPD. Sensitivity analyses were performed verify robustness findings. Mediation analysis conducted proteins in metabolism-COPD pathway. We constructed protein-protein interaction (PPI) network explored potential mechanism through gene ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment. Single-cell sequencing transcriptome datasets for auxiliary validation. Finally, experimental validation using human lung tissue. identified 63 10 metabolite ratios, 48 that associated with COPD, all which exhibited relationships. Furthermore, three as mediators metabolite-to-COPD PPI network, GO KEGG enrichment revealed biological pathways they involved. Validation expression intermediary tissue NRXN3 expressed endothelial cells exerted protective effect against COPD development. The among These findings offer novel insights into metabolism-inflammation-COPD mechanisms, suggesting interventions targeting metabolic processes may represent promising strategy preventing onset or progression

Language: Английский

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Gut microbiome links obesity to type 2 diabetes: insights from Mendelian randomization

BMC Microbiology, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 27, 2025

Research has established links between the gut microbiome (GM) and both obesity type 2 diabetes (T2D), which is much discussed, but underexplored. This study employed body mass index (BMI) as measurement of to delve deeper into correlations from a genetic perspective. We performed Mendelian randomization (MR) analysis examine causal effects GM on T2D BMI, vice versa. Genome-wide association (GWAS) summary datasets were utilized for analysis, including (N = 933,970), BMI 806,834), two international consortium MiBioGen (211 taxa, N 18,340) Dutch Microbiome Project (DMP) (207 7,738). These mainly cover European populations, with additional cohorts Asia other regions. To further explore potential mediating role in connections T2D, their interaction patterns summarized network. MR identified 9 taxa that showed protective properties against T2D. Seven species within Firmicutes Bacteroidales phyla DMP, (Odds Ratio (OR): 0.94-0.95). Conversely, components contributing abundance 12 associated increased risks (OR: 1.04-1.12). Furthermore, may elevate seven 1.03-1.08) reduce six 0.93-0.97). In influence component composition, affected 52 bacterial 28 decreasing 0.75-0.92) 24 increasing 1.08-1.27). Besides, abundances 25 negatively correlated 0.95-0.99), while positive detected 14 1.01-1.05). Notably, we uncovered 11 genetically formed an interactive Our findings provide evidence GM-mediated The identification relevant offers valuable insights these diseases.

Language: Английский

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Natural Compounds Exert Anti‐Obesity Effects by Regulating Cytokines

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

ABSTRACT Obesity, along with its associated health risks such as hypertension, hyperlipidemia, Type 2 diabetes, stroke, metabolic syndrome, asthma, and cancer, constitutes a significant global burden, contributing substantially to morbidity mortality. Cytokines, group of secreted signaling proteins, are crucial in initiating, maintaining, resolving immune responses. Although cytokines have unique advantages regulating functions, their therapeutic application for obesity remains limited clinical practice. Natural compounds, known structural diversity low toxicity, become valuable resource drug development. Many natural compounds shown anti‐obesity effects. This review comprehensively examines the mechanisms underlying obesity, specific focus on roles cytokines, inflammatory adipokines, growth factors. Additionally, it highlights regulatory interactions between gut microbiota obesity. The critically analyzes current pharmacological interventions summarizes advanced methodologies identifying potential compounds. Finally, identifies promising that modulate cytokine activity prevent or treat assesses complementary alternative therapies.

Language: Английский

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Magnesium is a key trace element in obstructive sleep apnea: evidence from Mendelian randomization analysis and NHANES database

Respiratory Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 108158 - 108158

Published: May 1, 2025

Language: Английский

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Identification of 1,400 metabolites as mediators of obesity in 473 gut microbiota taxa: a mediation Mendelian randomization study

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

ABSTRACT Obesity is a global health problem driven by genetic, endocrine, and environmental factors. Gut microbiota significantly influences obesity, yet causal relationships underlying pathways remain elusive. The objective of the study was to investigate between gut microbiota, metabolites, obesity; elucidate potential mediating obesity onset; identify novel genes; explore impact plasma proteins on risk. Bidirectional two-sample Mendelian randomization (MR) were used relationships. Mediation analyses identified mechanisms linking obesity. Pathway protein-protein interaction assessed genetic protein associations. MR analysis results 11 species with associations 69 metabolites that causally related seven bacteria relationships, mediated metabolites. Single nucleotide polymorphisms (SNP)-related gene set enrichment revealed clustering in concentration genes enriched for phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) membrane-related signaling pathways. Fms-related receptor tyrosine 1 (FLT1), growth-associated 43 (GAP43), SLIT NTRK-like family member (SLITRK1) had protective effects against This links bacteria, therapeutic targets. Findings deepen understanding obesity’s complex suggest prevention treatment strategies, emphasizing IMPORTANCE pioneered use approaches mediator confirm relationship also explored how these factors work together promote through specific interactions. finding provides theoretical basis targets precision medicine strategies which great clinical significance. In addition, identification as biomarkers opens up new avenues tailoring intervention

Language: Английский

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Cytokine concentration in peripheral blood of patients with childhood obesity

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 30, 2025

Introduction Obesity is marked by chronic inflammation, with research showing notable changes in cytokines. However, systematic investigations into cytokine level are still lacking. This study compared the concentrations of various cytokines peripheral blood healthy controls and obese children. Methods Peripheral samples from test cohort including 5 children obesity were used to evaluate concentration levels 48 inflammatory Bio-Plex assay. Diet-induced (DIO) mice assess whether there significant differences expression MIP-1b, PDGF-BB. validation 44 PDGF-BB, IP-10, IL-6, IL-9 TNF-β. Results In assay, MIP-1b PDGF-BB between Additionally, IL-9, TNF-β exhibited a trend difference two groups. no observed control DIO mice. Notably, we found that IL-6 serum children, suggesting may play key role response associated obesity. Discussion summary, our emphasizes importance other childhood suggests future should further explore specific roles these pathophysiological states obesity, aiming provide new strategies for prevention treatment

Language: Английский

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Gut Microbiota in Lactose Intolerance: A Mendelian Randomization Study on Microbial Mechanisms and Potential Links to Tumor Inflammatory Microenvironments

Mediators of Inflammation, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Previous observational studies have suggested an association between the composition of intestinal microbiome and lactose intolerance (LI). However, causal direction remains unclear. This study utilized Mendelian randomization (MR) to rigorously evaluate potential link gut LI. Methods: Genome‐wide (GWASs) summary statistics for microbiota LI were sourced from previously published GWAS studies. Multiple methods, such as Simple mode, MR‐Egger regression, weighted median, inverse variance‐weighted (IVW), model, used determine relationship To validate primary findings MR analyses, several sensitivity analyses conducted. Furthermore, a reverse analysis was executed on bacterial taxa identified with risk, aiming possibility causation. Results: The IVW results revealed that genus Lachnospiraceae UCG008 (OR = 0.584, 95%CI 0.356–0.958, p 0.0330), Eubacterium hallii group 0.467, 95% CI 0.242–0.899, 0.023), Ruminococcus gauvreauii 0.506, 0.2653–0.968, 0.039) protective effect against In contrast, Holdemania 1.86, 1.105–3.131, 0.0194) displayed predisposing effect. Sensitivity did not detect any outlier single‐nucleotide polymorphisms (SNPs). Further reinforced specific compositions No evidence causality in analysis. Conclusions: From genetic standpoint, this indicates variations only underscores microbiota‐centric treatments but also provides foundation exploring role development. mechanism treatment IL is conducive discovery new therapeutic targets IL.

Language: Английский

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