The causal relationship between gut microbiota and biliary tract cancer: comprehensive bidirectional Mendelian randomization analysis

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: March 15, 2024

Background Growing evidence has shown that gut microbiome composition is associated with Biliary tract cancer (BTC), but the causality remains unknown. This study aimed to explore causal relationship between microbiota and BTC, conduct an appraisal of microbiome’s utility in facilitating early diagnosis BTC. Methods We acquired summary data for Genome-wide Association Studies (GWAS) pertaining BTC (418 cases 159,201 controls) from Biobank Japan (BBJ) database. Additionally, GWAS relevant (N = 18,340) were sourced MiBioGen consortium. The primary methodology employed analysis consisted Inverse Variance Weighting (IVW). Evaluations sensitivity carried out through utilization multiple statistical techniques, encompassing Cochrane’s Q test, MR-Egger intercept evaluation, global test MR-PRESSO, a leave-one-out methodological analysis. Ultimately, reverse Mendelian Randomization was conducted assess potential reciprocal causality. Results outcomes derived IVW substantiated presence Family Streptococcaceae (OR 0.44, P 0.034), Veillonellaceae 0.46, 0.018), Genus Dorea 0.29, 0.041) exerted protective influence against Conversely, Class Lentisphaeria 2.21, 0.017), Lachnospiraceae FCS020 Group 2.30, 0.013), Order Victivallales 0.017) adverse impact. To any effect, we used as exposure outcome, this revealed associations five different types microbiota. disclosed absence empirical indicators either heterogeneity or pleiotropy. Conclusion investigation represents inaugural identification indicative supporting beneficial detrimental relationships risk determined MR methodologies. These could hold significance formulation individualized therapeutic strategies at prevention survival enhancement.

Language: Английский

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The causal relationship between gut microbiota and constipation: a two-sample Mendelian randomization study

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

Published: Aug. 19, 2024

Constipation is one of the most common gastrointestinal disorders afflicting population, with recent observational studies implicating dysfunction gut microbiota in constipation. Despite indicating a relationship, clear causality remains unclear. This study aims to use two-sample Mendelian randomization (MR) establish clearer causal relationship between two.

Language: Английский

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Causal associations between human gut microbiota and osteomyelitis: a Mendelian randomization study

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: April 9, 2024

Background Recent studies have emphasized the role of gut microbiota in onset and progression osteomyelitis. However, exact types their mechanisms action remain unclear. Additionally, there is a lack theoretical support for treatments that improve osteomyelitis by altering microbiota. Methods In our study, we utilized largest genome-wide association study (GWAS) meta-analysis to date from MiBioGen consortium, involving 13,400 participants. The GWAS data were sourced UK Biobank, which included 4,836 cases 486,484 controls. We employed two-sample Mendelian randomization framework detailed investigation into causal relationship between Our methods inverse variance weighting, MR-Egger, weighted median, mode approaches. applied Cochran’s Q statistic assess heterogeneity instrumental variable. Results At class level, Bacilli Bacteroidia positively correlated with risk order only Bacteroidales showed positive genus an increased abundance Butyricimonas , Coprococcus3 Tyzzerella3 was associated osteomyelitis, whereas Lachnospira negatively associated. Sensitivity analyses no evidence or pleiotropy. Conclusion This reveals classes Bacteroidia, Bacteroidales, genera are implicated increasing while reduced risk. Future investigations warranted elucidate precise through these specific bacterial groups influence pathophysiology

Language: Английский

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Investigating casual association among gut microbiome and esophageal cancer: A Mendelian randomization study

Medicine, Journal Year: 2025, Volume and Issue: 104(8), P. e41563 - e41563

Published: Feb. 21, 2025

The gut microbiota has been strongly linked to gastrointestinal cancer, but the relationship between and esophageal cancer (EC) is still not fully understood. We conducted a 2-sample Mendelian randomization (MR) study unveil potential impact of intestinal microorganisms on EC in East Asian populations. In order delve deeper into causal EC, we MR analysis, utilizing 211 single nucleotide polymorphisms associated with microbiota, sourced from largest genome-wide association for our analysis. To estimate relationship, employed inverse variance weighting method. addition, assess influence pleiotropy, used MR-Egger regression Among 10 specific bacterial taxa identified using as being risk observed positive family Bacteroidaceae ( P = .04), genus Bacteroides Bilophila .02), Candidatus Soleaferrea .02) while Victivallaceae .03), Eubacterium coprostanoligenes .01), Catenibacterium Coprococcus2 unknowngenus.id.959 unknowngenus.id.1868 .01) may be reduced EC. Our analysis indicate probable development advancement These findings offer novel perspectives possible application targeted bacteria prevention management

Language: Английский

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Intestinal flora was associated with occurrence risk of chronic non-communicable diseases

World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(11)

Published: March 12, 2025

BACKGROUND The intestinal flora (IF) has been linked to risks of non-communicable diseases, especially various cancers, stroke, and Alzheimer’s disease. However, many uncertainties these associations during different stages growth, development, aging still exist. Therefore, further in-depth explorations are warranted. AIM To explore the human IF with disease achieve more accurate convincing conclusions. METHODS Cohort, cross-sectional, case-control, Mendelian randomization studies published in PubMed Web Science databases until December 31, 2023 were systematically reviewed clarify at genus level which grouped accordance 10th revision International Classification Diseases. RESULTS In total, 57 included quantitatively examine influence on 30 diseases aging. Population confirmed positive abundances Bifidobacterium Ruminococcus multiple sclerosis. CONCLUSION These findings contribute a deeper understanding roles provide novel evidence for effective strategies prevention treatment diseases. future, it will be necessary greater variety research techniques uncover specific mechanisms by gut microbiota trigger conduct temporal relationship between alterations so as causal accurately.

Language: Английский

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Gut microbiota and autism spectrum disorders: a bidirectional Mendelian randomization study

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Dec. 14, 2023

Background In recent years, observational studies have provided evidence supporting a potential association between autism spectrum disorder (ASD) and gut microbiota. However, the causal effect of microbiota on ASD remains unknown. Methods We identified summary statistics 206 from MiBioGen study, data were obtained latest Psychiatric Genomics Consortium Genome-Wide Association Study (GWAS). then performed Mendelian randomization (MR) to determine relationship using inverse variance weighted (IVW) method, simple mode, MR-Egger, median, model. Furthermore, we used Cochran’s Q test, MR-Egger intercept Randomization Pleiotropy RESidual Sum Outlier (MR-PRESSO), leave-one-out analysis identify heterogeneity pleiotropy. Moreover, Benjamin-Hochberg approach (FDR) was employed assess strength connection exposure outcome. reverse MR that found be causally associated with in forward examine relationships. The enrichment analyses analyze biological function at last. Results Based results IVW results, genetically predicted family Prevotellaceae genus Turicibacter had possible positive (IVW OR=1.14, 95% CI: 1.00-1.29, P =3.7×10 −2 ), four protective ASD: Dorea (OR=0.81, 0.69-0.96, =1.4×10 Ruminiclostridium5 =1.5×10 Ruminococcus1 (OR=0.83, 0.70-0.98, =2.8×10 Sutterella (OR=0.82, 0.68-0.99, =3.6×10 ). After FDR multiple-testing correction further observed there two still significant OR=1.24; 1.09-1.40, =9.2×10 -4 ) strongly positively correlated RuminococcaceaeUCG005 OR=0.78, 0.67-0.89, =6.9×10 −4 negatively ASD. sensitivity excluded influence horizontal Conclusion Our findings reveal several microbiomes These deepen our comprehension role ASD’s pathology, providing foothold for novel ideas theoretical frameworks prevent treat this patient population future.

Language: Английский

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Cholesterol Gallstones and Long-Term Use of Statins: Is Gut Microbiota Dysbiosis Bridging over Uncertainties?

Diagnostics, Journal Year: 2024, Volume and Issue: 14(12), P. 1234 - 1234

Published: June 12, 2024

A total of 300 research participants—200 consecutive patients diagnosed with dyslipidemia (100 statin (+), treated for at least five years, and 100 (−)) healthy controls—were included in this observational study. The aim the study was to deliver insights into relationship between long-term use statins gallstone disease (GSD), as well background particularities gut microbiota. All participants underwent clinical examination, laboratory workups, stool microbiology/stool 16S r RNA, next-generation sequencing, abdominal ultrasound/CT exams. Results: presented similarities related age, gender, location. Patients displayed comparable heredity GSs, metabolic issues, co-morbidities. Gut dysbiosis (DB) present 54% (−) vs. 35% (+) (p = 0.0070). GSs were 14% group 5% 0.0304). Severe dysbiosis, a significant reduction biodiversity, an increase LPS bacteria, notable decrease mucin-degrading mucosa-protective butyrate-producing bacteria observed group. Strong positive correlations GSD diabetes/impaired glucose tolerance (r 0.3368, p 0.0006), obesity 0.3923, < 0.0001), nonalcoholic fatty liver 0.3219, 0.0011), DB 0.7343, negative alcohol −0.2305, 0.0211), observed. multiple regression equation demonstrated that only (95% CI: 0.3163 0.5670; 0.0001) 0.01431 0.2578; 0.0289) independent risk factors predicting statins. Conclusion: dyslipidemic associated low developing GSs. microbiota characterized by imbalance various functional alterations found be patients.

Language: Английский

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Role of inflammatory cytokines and the gut microbiome in vascular dementia: insights from Mendelian randomization analysis

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

Published: Aug. 23, 2024

Background Both inflammatory cytokines and the gut microbiome are susceptibility factors for vascular dementia (VaD). The trends in overall changes dynamics of composition influenced by a variety factors, making it difficult to fully explain different effects both on subtypes VaD. Therefore, this Mendelian randomization (MR) study identified members that influence risk developing VaD their causal effects, investigated whether mediators affecting Methods We obtained pooled genome-wide association (GWAS) data 196 microbiota 41 used GWAS six subtypes, namely, (mixed), (multiple infarctions), (other), (subcortical), (sudden onset), (undefined). inverse-variance weighted (IVW) method as primary MR analysis method. conducted sensitivity analyses reverse examine associations, enhancing reliability stability conclusions. Finally, we multivariable (MVMR) assess direct VaD, performed mediation explore were potential mediators. Results Our two-sample revealed relationships between microbiota: 7 14 constituents positively correlated with increased subtype risk, while 2 11 negatively decreased risk. After Bonferroni correction, interleukin-18 was an infarctions); macrophage migration inhibitory factor onset); interleukin-4 (other); Ruminiclostridium 6 Bacillales (undefined), respectively; Negativicutes Selenomonadales (mixed); Melainabacteria infarctions). Sensitivity no multilevel or heterogeneity inverse causality microbiota. MVMR results further confirmed , remain significant. Mediation showed not Conclusion This helps us better understand pathological mechanisms suggests value targeting increases decreases prevention intervention.

Language: Английский

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Causal links between gut microbiomes, cytokines and risk of different subtypes of epilepsy: a Mendelian randomization study

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: May 24, 2024

Objective Recent research suggests a potential link between the gut microbiome (GM) and epilepsy. We undertook Mendelian randomization (MR) study to determine possible causal influence of GM on epilepsy its various subtypes, explore whether cytokines act as mediators. Methods utilized Genome-Wide Association Study (GWAS) summary statistics examine relationships GM, cytokines, four subtypes. Furthermore, we assessed mediate relationship Significant GMs were further investigated using transcriptomic MR analysis with genes mapped from FUMA GWAS. Sensitivity analyses reverse conducted for validation, false discovery rate (FDR) correction was applied multiple comparisons. Results pinpointed 30 Notably, Family Veillonellaceae (OR:1.03, 95%CI:1.02–1.05, p = 0.0003) consistently showed strong positive association child absence epilepsy, this endured even after FDR ( -FDR &lt; 0.05). Seven significantly associated A mediating role has not been demonstrated. tests validated primary outcomes. Additionally, no causality detected significant Of notable GMs, like BLK, FDFT1, DOK2, FAM167A, ZSCAN9, RNGTT, RBM47, DNAJC21, SUMF1, TCF20, GLO1, TMTC1, VAV2, RNF14 exhibited profound correlation risk factors Conclusion Our validates in there evidence that play This could provide fresh perspectives prevention treatment

Language: Английский

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Genetically predicted the causal relationship between gut microbiota and the risk of polymyositis/dermatomyositis: a Mendelian randomization analysis

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

Published: Aug. 21, 2024

Introduction Observational studies suggest associations between gut microbiota and polymyositis (PM) dermatomyositis (DM), but causal relationships are unclear. We investigate the effects of on PM DM, providing insights hoping to provide for future treatment prevention. Methods Summary statistics were obtained from a multi-ethnic Genome Wide Association Studies (GWAS) meta-analysis, including 119 taxa 18,340 Europeans. PM/DM extracted GWAS analyses. Mendelian randomization (MR) with IVW, MR-Egger, weighted median methods was performed. Sensitivity analyses addressed heterogeneity pleiotropy. Of bacterial genera studied, six showed links. Results Alloprevotella (OR: 3.075, 95% CI: 1.127–8.386, p = 0.028), Ruminococcaceae UCG003 4.219, 1.227–14.511, 0.022), Dialister 0.273, 0.077–0.974, 0.045) associated PM. Anaerotruncus 0.314, 0.112–0.882, UCG002 2.439, 1.173–5.071, 0.017), Sutterella 3.392, 1.302–8.839, 0.012) related DM. validated these Discussion establish , UCG003, Common microbiota, like have significant clinical implications. These findings open up greater possibilities contribute development monitoring in patients PM/DM.

Language: Английский

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