Investigating the causal role of the gut microbiota in esophageal cancer and its subtypes: a two-sample Mendelian randomization study

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 4, 2024

Abstract Background Through research on the gut microbiota (GM), increasing evidence has indicated that GM is associated with esophageal cancer (ESCA). However, specific cause-and-effect relationship remains unclear. In this study, Mendelian randomization (MR) analysis was applied to investigate causal between and ESCA, including its subtypes. Methods We collected information 211 GMs acquired data ESCA subtypes through genome-wide association studies (GWASs). The primarily assessed using inverse variance weighted (IVW) method. Additionally, we median estimator (WME) method, MR–Egger mode, simple mode provide further assistance. Subsequent these analyses, sensitivity conducted intercept test, MR-PRESSO global leave-one-out Result Following our assessment five methods analysis, identified seven potential relationships At genus level, Veillonella Coprobacter were positively correlated whereas Prevotella9 , Eubacterium oxidoreducens group Turicibacter negatively ESCA. case of adenocarcinoma (EAC), Flavonifractor exhibited a positive correlation, while Actinomyces negative correlation. Conclusion Our study revealed subtypes, offering novel insights for advancement diagnosis treatment.

Language: Английский

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Blessing or curse: how the epigenetic resolution of host-transposable element conflicts shapes their evolutionary dynamics

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 291(2020)

Published: April 9, 2024

Transposable elements (TEs) are selfish genetic whose antagonistic interactions with hosts represent a common conflict in eukaryotes. To resolve this conflict, have widely adopted epigenetic silencing that deposits repressive marks at TEs. However, mechanism is imperfect and fails to fully halt TE replication. Furthermore, can inadvertently spread adjacent functional sequences, phenomenon considered 'curse' of resolution. Here, we used forward simulations explore how its harmful side effects shape the evolutionary dynamics TEs their hosts. Our findings reveal allows stably coexist under wide range conditions, because underlying molecular mechanisms give rise copy-number dependency strength silencing. Interestingly, contrary intuitive expectations should evolve be as strong possible, found selective benefit for modifier alleles weaken biologically feasible conditions. These results dual nature silencing, both positive negative effects, complicates trajectory makes it challenging determine whether 'blessing' or 'curse'.

Language: Английский

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Causal Associations Between Gut Microbiota and Cerebrovascular Diseases

World Neurosurgery, Journal Year: 2024, Volume and Issue: 183, P. e587 - e597

Published: Jan. 6, 2024

Language: Английский

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Investigating the correlation between gut microbiota and prostate cancer through a two-sample Mendelian randomization analysis

Medicine, Journal Year: 2025, Volume and Issue: 104(1), P. e41141 - e41141

Published: Jan. 3, 2025

Previous studies in observational epidemiology have suggested a potential correlation between the gastrointestinal tract microbiota and prostate cancer. However, causal relationship 2 remains uncertain, our objective was to thoroughly examine influence of gut microbiome on progression In this study, we focused investigating as an exposure factor, specifically analyzing data from MiBioGen consortium, which had substantial sample size 18,340 participants. As disease outcome, utilized cancer FinnGen genome-wide association involved 13,216 To establish relationships, conducted comprehensive Mendelian randomization analysis employing multiple methods, including inverse variance-weighted, randomization-Egger, maximum likelihood, weighted median approaches. Additionally, performed sensitivity address issues such heterogeneity horizontal pleiotropy, ensuring robustness findings. The results obtained through variance-weighted revealed that certain microbial groups exhibited protective effect Specifically, phylum Verrucomicrobia, particularly family Rikenellaceae, genera Anaerotruncus, Eisenbergiella, Olsenella, Parabacteroides were found beneficial impact. Conversely, class Bacilli, Erysipelotrichia, order Erysipelotrichales, Lactobacillales, Erysipelotrichaceae, Marvinbryantia, Romboutsia, Ruminococcaceae UCG002, Sutterella adverse did not reveal any outliers, further strengthening validity results. summarize, cause-and-effect connection discovered various types Nevertheless, additional randomized controlled experiments are required for validation.

Language: Английский

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The relationship between genetic prediction of 486 blood metabolites and the risk of COPD: mendelian randomization study

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

Published: March 1, 2025

Metabolic disorders are an important feature of chronic lung disease. Patients diagnosed with obstructive pulmonary disease (COPD) have been found to experience metabolic disorders. Nonetheless, evidence on the causal role circulating metabolites in promoting or preventing COPD is still lacking. Conducting a methodical examination connection between blood and can aid identifying fresh objectives for screening prevention COPD. Therefore, we performed two-sample Mendelian randomization (MR) analysis evaluate association 486 metabolites.We used MR techniques genome-wide study (GWAS) data correlation serum metabolites. To impact risk COPD, predominantly employed inverse variance weighting (IVW) methodology. The MR-Egger regression test was assess multiple validity, while presence heterogeneity examined using Cochran's Q test. ensure reliability findings, leave-one-out conducted. Bonferroni correction adjust comparisons, ensuring rigorous validation our results.After filtering by IVW sensitivity analysis, identified 10 known including fructose, margarate (17:0), guanosine, 2-stearoylglycerophosphocholine, hexadecanedioate, lactate, 5-oxoproline, paraxanthine, phenyllactate (PLA) N-acetylglycine. Of these, 2-stearoylglycerophosphocholine hexadecanedioate metabolites, additionally, paraxanthine phenyllactate(PLA) N-acetylglycine protective In addition, five currently unknown chemical structures. Q-test showed no significant heterogeneity, Egger's intercept confirmed absence horizontal multidirectionality. Leave-one-out also proved analysis.We seven COPD-related risks eight human By combining genomics metabolism, it provides new insights into underlying mechanisms implications prevention.

Language: Английский

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Mitochondrial proteins and congenital birth defect risk: a mendelian randomization study

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

Published: April 14, 2025

Language: Английский

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Association between genetic prediction of 486 blood metabolites and the risk of idiopathic pulmonary fibrosis: A mendelian randomization study

Biomedical Reports, Journal Year: 2025, Volume and Issue: 22(3)

Published: Jan. 23, 2025

Metabolic disorders are a significant feature of fibrotic diseases. Nevertheless, the lack sufficient proof regarding cause‑and‑effect association between circulating metabolites and promotion or prevention idiopathic pulmonary fibrosis (IPF) persists. To assess causal IPF genetic proxies 486 blood metabolites, dual sample Mendelian randomization (MR) analysis was performed. Therefore, two‑sample MR technique genome‑wide study data were employed to serum IPF. produce primary outcomes, inverse variance weighted (IVW) applied, while stability dependability sensitivity using MR‑Egger Additionally, median, Cochran's Q‑test, Egger intercept test leave‑one‑out method used. The results present revealed total 21 in circulation that could affect risk (P_IVW<0.05). Among them, 10 compounds already known, namely cotinine [odds ratio (OR)=1.206; 95% confidence interval (CI), 1.002‑1.452; P=0.047], hypoxanthine (OR=0.225; CI, 0.056‑0.899; P=0.034), aspartyl phenylalanine (OR=4.309; 1.084‑17.131; P=0.038), acetyl‑carnitine (OR=5.767; 1.398‑23.789; P=0.015), 2‑aminobutyrate (OR=0.155; 0.033‑0.713; P=0.016), Docosapentaenoic acid (PubChem ID: 5497182; OR=0.214; 0.055‑0.833; P=0.026), octanoyl‑carnitine 177508; OR=3.398; 1.179‑9.794; P=0.023), alpha‑hydroxy‑isovalerate 857803‑94‑2; OR=0.324; 0.112‑0.931; P=0.036), 1,7‑dimethylurate 91611; OR=0.401; 0.172‑0.931; P=0.033) 1‑linoleoyl‑glycerophosphocholine 657272; OR=6.559; 1.060‑40.557; P=0.043). also identified 11 currently unknown chemical structures. Q‑test indicated there no heterogeneity, MR‑Egger's verified horizontal pleiotropy. retention one for plotting supported reliability analysis. Overall, current including with known composition which still awaiting determination. These findings provide novel insights further investigation mechanism underlying development

Language: Английский

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Causal relationship in gut microbiota and upper urinary urolithiasis using Mendelian randomization

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

Published: May 18, 2023

Several reports in recent years have found an association between gut microbiota and upper urinary urolithiasis. However, the causal relationship them remains to be clarified. Genetic variation is used as a tool Mendelian randomization for inference of whether exposure factors effect on disease outcomes. We selected summary statistics from large genome-wide study microbiome published by MiBioGen consortium with sample size 18,340 factor urolithiasis data FinnGen GWAS 4,969 calculi cases 213,445 controls outcome. Then, two-sample analysis was performed applying inverse variance-weighted, MR-Egger, maximum likelihood, weighted median. In addition, heterogeneity horizontal pleiotropy were excluded sensitivity analysis. IVW results confirmed that class Deltaproteobacteria (OR = 0.814, 95% CI: 0.666-0.995, P 0.045), order NB1n 0.833, 0.737-0.940, 3.15 × 10-3), family Clostridiaceae1 0.729, 0.581-0.916, 6.61 genus Barnesiella 0.695, 0.551-0.877, 2.20 Clostridium sensu_stricto_1 0.777, 0.612-0.986, 0.0380), Flavonifractor 0.711, 0.536-0.944, 0.0181), Hungatella 0.829, 0.690-0.995, 0.0444), Oscillospira 0.758, 0.577-0.996, 0.0464) had protective urolithiasis, while Eubacterium xylanophilum =1.26, 1.010-1.566, 0.0423) opposite effect. Sensitivity did not find outlier SNPs. summary, several genera we still need further randomized controlled trials validate.

Language: Английский

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Genetically predicted 486 blood metabolites concerning risk of systemic lupus erythematosus: a Mendelian randomization study

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 18, 2023

Abstract Metabolic abnormalities constitute a significant characteristic of systemic lupus erythematosus (SLE). We utilised two-sample Mendelian randomisation (MR) study to evaluate the potential causal association between 486 blood metabolites and SLE. Exposure data at metabolite level were extracted from 7824 European Genome-wide studies (GWAS). Preliminary analysis SLE GWAS FinnGen. The primary method for relied on random inverse variance weighting (IVW). To ensure robustness, sensitivity analyses included Cochran Q test, MR-Egger intercept MR-PRESSO, leave-one-out analysis. Steiger testing linkage disequilibrium score regression employed validate identified metabolites. This 12 metabolites, comprising six known chemical structures: 1,5-anhydroglucitol(1,5-AG) [odds ratio (OR) = 0.100, 95% confidence interval (CI): 0.015–0.773, P 0.027), gamma-glutamylthreonine (OR 0.077, CI: 0.010–0.574, 0.012), 5-dodecenoate(12:1n7) 0.205, 0.061–0.685, 0.010), linoleoylglycerophosphoethanolamine * 0.159, 0.027–0.933, 0.044), erythrose 88.331,95% CI:1.098–63.214, 0.040) 1-, adrenate (22:4n6) 9.876, 1.753–55.639, 0.001)]. Additionally, we found associations unknown X-06351 0.071, 0.006–0.817, 0.034), X-10810 4.268 1.260–14.459, 0.020), X-11412 5.418 1.068–27.487, 0.041), X-11905 0.551, 95%CI: 0.304–0.997, 0.049), X-12038 0.178 0.032–0.988, 0.045), X-12217 0.174 0.044–0.680, 0.014). offers evidence supporting relationship circulating which have structures that remain unidentified. These findings introduce new perspective further exploration mechanisms.

Language: Английский

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Causal association of genetically determined plasma metabolites with osteoarthritis: a two-sample Mendelian randomization study

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: June 28, 2024

Background We aimed to elucidate the causal relationship between plasma metabolites and vulnerability Osteoarthritis (OA), encompassing both hip OA knee OA. Methods conducted a two-way two-sample Mendelian randomization (MR) analysis investigate association of 1,400 with The Inverse Variance Weighted (IVW) model served as primary MR Analysis method, supplementary using Median (WM) Egger methods. To ensure robustness our findings, sensitivity analyses were performed, incorporating Cochran’s Q test, MR-Egger intercept MR-PRESSO, Leave-One-Out analyses. validate identified metabolites, we utilized Steiger test linkage disequilibrium score regression. Results A total 94 associated osteoarthritis, 60 106 IVW revealed that tryptophan levels showed strongest positive (OR [95% CI]: 1.119 [1.024, 1.223]), while X-24757 exhibited highest osteoarthritis 1.095 [1.032, 1.162]). Ethylparaben sulfate found have greatest 1.118 [1.015, 1.231]). Notably, metabolite X-2475 strong robust random effect across all three types osteoarthritis. Metabolic pathway pathogenesis in was mediated by acetylarginine, specifically four important metabolic pathways: ethanol degradation ( p = 0.044), amino sugar metabolism 0.090), fatty acid biosynthesis 0.095), aspartate 0.097816). Conclusion There is significant risk OA, well Additionally, are also linked Moreover, this study has crucial pathways which regulated acetylarginine. These findings provide valuable insights into potential biomarkers for highlight its prevention clinical intervention.

Language: Английский

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