Causal relationship between gut microbiota and risk of gastroesophageal reflux disease: a genetic correlation and bidirectional Mendelian randomization study

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

Published: Feb. 21, 2024

Background Numerous observational studies have identified a linkage between the gut microbiota and gastroesophageal reflux disease (GERD). However, clear causative association GERD has yet to be definitively ascertained, given presence of confounding variables. Methods The genome-wide study (GWAS) pertaining microbiome, conducted by MiBioGen consortium comprising 18,340 samples from 24 population-based cohorts, served as exposure dataset. Summary-level data for were obtained recent publicly available involving 78 707 cases 288 734 controls European descent. inverse variance-weighted (IVW) method was performed primary analysis, other four methods used supporting analyses. Furthermore, sensitivity analyses encompassing Cochran’s Q statistics, MR-Egger intercept, MR-PRESSO global test, leave-one-out methodology carried out identify potential heterogeneity horizontal pleiotropy. Ultimately, reverse MR assessment investigate causation. Results IVW method’s findings suggested protective roles against Family Clostridiales Vadin BB60 group ( P = 0.027), Genus Lachnospiraceae UCG004 (P 0.026), Methanobrevibacter Phylum Actinobacteria 0.019). In contrast, Class Mollicutes 0.037), Anaerostipes 0.049), Tenericutes 0.024) emerged risk factors. assessing causation with outcome, indicate that leads dysbiosis in 13 distinct classes. results’ reliability confirmed thorough assessments Conclusions For first time, analysis indicates genetic link abundance changes risk. This not only substantiates intestinal microecological therapy GERD, but also establishes basis advanced research into role etiology GERD.

Language: Английский

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Gut microbiota, inflammatory cytokines and gastro-esophageal reflux disease: A Mendelian randomization analysis

Medicine, Journal Year: 2025, Volume and Issue: 104(5), P. e41386 - e41386

Published: Jan. 31, 2025

Gut microbiota has been recognized as an extrahepatic manifestation of gastro-esophageal reflux disease (GERD) in observational studies. However, the directionality and causality association whether cytokines act a mediator remain unclear. We aim to estimate casual relationship between gut microbiota, inflammatory GERD using 2-sample Mendelian randomization method. cytokines, were identified summary data from genome-wide studies FinnGen consortium. The primary method for causal estimation was inverse-variance weighted approach, complemented by range sensitivity analyses aimed at assessing heterogeneity, horizontal pleiotropy, robustness findings. Furthermore, mediation analysis conducted evaluate GERD, with 5 calculate mediated proportions. found 3 positive negative associations observed genetic predisposition GERD. Additionally, 2 Our unveiled that TNF-related apoptosis-inducing ligand levels (TRAIL) relationships genera Family XIII UCG001 Senegalimassilia, effects 6 bacterial traits, Notably, we furnished evidence linking TRAIL substantial proportion risk attributed genus thereby mediating These findings offer novel avenues therapeutic interventions targeting individuals

Language: Английский

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Identification of lipid metabolism related immune markers in atherosclerosis through machine learning and experimental analysis

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

Published: Feb. 25, 2025

Atherosclerosis is a significant contributor to cardiovascular disease, and conventional diagnostic methods frequently fall short in the timely accurate detection of early-stage atherosclerosis. Abnormal lipid metabolism plays critical role development Consequently, identification new markers essential for precise diagnosis this condition. The datasets related atherosclerosis utilized research were obtained from GEO database (GSE2470, GSE24495, GSE100927 GSE43292). ssGSEA technique was first assess scores samples affected by atherosclerosis, thereby aiding discovery important regulatory genes linked via WGCNA. Following this, differential expression analysis functional evaluations carried out, after which various machine learning approaches employed determine A model then developed validated through several algorithms. Furthermore, molecular docking studies conducted analyze binding affinity these key with therapeutic agents also used measure immune cell atherosclerotic samples, exploration connection between cells. Finally, variations identified pivotal confirmed experimental validation. WGCNA 302 metabolism-related revealed that are associated multiple pathways. Through further screening using algorithms, APLNR, PCDH12, PODXL, SLC40A1, TM4SF18, TNFRSF25 as we constructed predict occurrence high accuracy, indicated six have potential drug targets. Additionally, algorithm association levels experimentally confirmed. Our study introduces novel emphasizes their immune-related This provides valuable approach predictive targeted therapy

Language: Английский

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Causal relationship between gut microbiota and risk of esophageal cancer: evidence from Mendelian randomization study

Aging, Journal Year: 2024, Volume and Issue: 16(4), P. 3596 - 3611

Published: Feb. 15, 2024

Background: The causative implications remain ambiguous. Consequently, this study aims to evaluate the putative causal relationship between gut microbiota and Esophageal cancer (EC). Methods: genome-wide association (GWAS) pertaining microbiome, derived from MiBioGen consortium-which consolidates 18,340 samples across 24 population-based cohorts-was utilized as exposure dataset. Employing GWAS summary statistics specific EC patients sourced Catalog leveraging two-sample Mendelian randomization (MR) methodology, principal analytical method applied was inverse variance weighted (IVW) technique. Cochran's Q statistic discern heterogeneity inherent in data set. Subsequently, a reverse MR analysis executed. Results: Findings IVW technique elucidated that Family Porphyromonadaceae (P = 0.048) Genus Candidatus Soleaferrea function deterrents against development. In contrast, Catenibacterium 0.044), Eubacterium coprostanoligenes group 0.038), Marvinbryantia 0.049), Ruminococcaceae UCG010 0.034), Ruminococcus1 0.047), Sutterella 0.012) emerged prospective risk contributors for EC. To assess effect, we used outcome, revealed associations seven different types of microbiota. robustness findings substantiated through comprehensive pleiotropy evaluations. Conclusions: This research identified certain microbial taxa either protective or detrimental elements EC, potentially offering valuable biomarkers asymptomatic diagnosis therapeutic interventions

Language: Английский

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The Role of the Gut Microbiome in the Development of Acute Pancreatitis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1159 - 1159

Published: Jan. 18, 2024

With the explosion research on gut microbiome in recent years, much insight has been accumulated comprehending crosstalk between microbiota community and host health. Acute pancreatitis (AP) is one of gastrointestinal diseases associated with significant morbidity subsequent mortality. Studies have elucidated that are engaged pathological process AP. Herein, we summarize major roles development We then portray association dysbiosis severity Finally, illustrate promises challenges arise when seeking to incorporate acute treatment.

Language: Английский

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Gut microbiome changes associated with chronic pancreatitis and pancreatic cancer: A systematic review and Meta-analysis

International Journal of Surgery, Journal Year: 2024, Volume and Issue: 110(9), P. 5781 - 5794

Published: June 7, 2024

Background: The study of changes in the microbiome chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) holds significant potential for developing noninvasive diagnostic tools as well innovative interventions to alter progression diseases. This systematic review meta-analysis aimed analyze detail taxonomic functional characteristics gut patients with CP PDAC. Methods: Two researchers conducted a search across public databases gather all published research up June 2023. Diversity microbiota composition are main outcomes authors focus on. Results: included 14 studies, involving total 1511 individuals PDAC ( n =285), =342), control =649) groups. Our results show difference between PDAC/CP compared healthy controls (HC), evidenced by slight decrease α-diversity, including Shannon (SMD=−0.33; P =0.002 SMD=−0.59; <0.001, respectively) statistically β-diversity <0.05). pooled showed that at phylum level, proportion Firmicutes was lower than HC patients. At genus more two studies demonstrated four genera were significantly increased (e.g. Escherichia-Shigella Veillonella ). had an increase Klebsiella ) eight Coprococcus Bifidobacterium HC. Functional/metabolomics from various also differences In addition, this found no Conclusions: Current evidence suggests is associated PDAC/CP, commonly reflected reduction beneficial species pathogenic species. Further needed confirm these findings explore therapeutic possibilities.

Language: Английский

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A causal relationship between distinct immune features and acute or chronic pancreatitis: results from a mendelian randomization analysis

Pancreatology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Immune Cells and Intracerebral Hemorrhage: A Causal Investigation Through Mendelian Randomization

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

ABSTRACT Background The involvement of immune cells in the pathophysiology intracerebral hemorrhage (ICH) is becoming increasingly recognized, yet their specific causal contributions remain uncertain. objective this research to uncover potential interactions between diverse and ICH using Mendelian randomization (MR) analysis. Methods Genetic variants associated with 731 cell traits were sourced from a comprehensive genome‐wide association study (GWAS) involving 3757 participants. Summary statistics data for acquired FinnGen, comprising 4056 cases 371,717 controls. principal analytical tool utilized our was inverse‐variance weighted (IVW) method, incorporated as key component two‐sample MR approach. To mitigate biases verify stability conclusions drawn primary methods, series sensitivity analyses performed. Results analysis elucidated 33 associations, B (eight traits), conventional dendritic (cDC, two maturation stages T (two monocytes myeloid (five TBNK (six regulatory (Treg, eight traits). DP (CD4+CD8+) %T (OR = 0.83, CI 0.72–0.96, p 0.013) exhibited strongest protective effect. In contrast, transitional AC 1.09, 1.02–1.16, 0.006) IgD− CD27− %lymphocyte 1.08, 1.00–1.17, 0.045) showed higher tendency increase risk. validated robustness consistency these results. Conclusion Our provides robust evidence substantiating relationship immunophenotypes identification findings significantly enhances understanding pathogenic mechanisms underlying ICH, particularly pertaining system. This breakthrough paves way innovative clinical pharmaceutical opportunities, potentially promoting development targeted therapies enhanced strategies managing preventing ICH.

Language: Английский

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Genetically predicted causal link between the plasma lipidome and pancreatic diseases: a bidirectional Mendelian randomization study

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 15, 2025

Recent studies have increasingly emphasized the strong correlation between lipidome and risk of pancreatic diseases. To determine causality, a Mendelian randomization (MR) analysis was performed to identify connections Statistics from genome-wide association study plasma lipidome, which included diverse array 179 lipid species, were obtained GeneRISK cohort with 7,174 participants. Genetic associations four types pancreatitis cancer sourced R11 release FinnGen consortium. Two datasets UK Biobank employed as validation cohort. MR conducted assess relationship genetically predicted these Inverse variance weighted adopted main statistical method. Bayesian for further verification. The MR-Egger intercept test pleiotropy Cochrane's Q statistics heterogeneity ensure robustness. yielded significant evidence that 26, 25, 2, 19 species correlated outcomes pancreatitis, 8 cancer. Notably, sterol ester (27:1/20:2) levels (OR: 0.84, 95% CI: 0.78-0.90, P = 5.79 × 10-7) significantly associated acute phosphatidylcholine (17:0_20:4) 0.89, 0.84-0.94, 1.78 10-4) (27:1/20:4) 0.90, 0.86-0.95, 2.71 chronic after Bonferroni-corrected test. As validation, 14 9 Biobank. Some classes showed effects both in consortium datasets. findings this indicate potential genetic predisposition linking diseases good prospects future disease clinical trials.

Language: Английский

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New insights into the mechanisms of the immune microenvironment and immunotherapy in osteosarcoma

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

Published: Jan. 17, 2025

Osteosarcoma, a malignant bone tumor primarily affecting adolescents, is highly invasive with poor prognosis. While surgery and chemotherapy have improved survival for localized cases, pulmonary metastasis significantly reduces to approximately 20%, highlighting the need novel treatments. Immunotherapy, which leverages immune system target osteosarcoma cells, shows promise. This review summarizes biological characteristics of osteosarcoma, mechanisms metastasis, microenvironment (TME). It involves recent immunotherapy advances, including monoclonal antibodies, vaccines, cell therapies, checkpoint inhibitors, oncolytic viruses, discusses combining these standard

Language: Английский

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