Causal relationship between gut microbiota and cancers: a two-sample Mendelian randomisation study

BMC Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Feb. 21, 2023

Abstract Background Evidence from observational studies and clinical trials suggests that the gut microbiota is associated with cancer. However, causal association between cancer remains to be determined. Methods We first identified two sets of based on phylum, class, order, family, genus level information, data were obtained IEU Open GWAS project. then performed two-sample Mendelian randomisation (MR) determine whether causally eight types. Furthermore, we a bi-directional MR analysis examine direction relations. Results 11 relationships genetic liability in microbiome cancer, including those involving Bifidobacterium . found 17 strong associations Moreover, 24 using multiple datasets. Conclusions Our revealed was cancers may useful providing new insights for further mechanistic microbiota-mediated

Language: Английский

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Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 24, 2022

Growing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship.

Language: Английский

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Causal effects of gut microbiota on diabetic retinopathy: A Mendelian randomization study

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 8, 2022

Background Previous researches have implicated a vital association between gut microbiota (GM) and diabetic retinopathy (DR) based on the of “gut-retina” axis. But their causal relationship has not been elucidated. Methods Instrumental variables 211 GM taxa were obtained from genome wide study (GWAS), Mendelian randomization was carried out to estimate effects DR risk FinnGen GWAS (14,584 cases 202,082 controls). Inverse variance weighted (IVW) is main method analyze causality, MR results are verified by several sensitive analyses. Results As for taxa, IVW confirmed that family- Christensenellaceae ( P = 1.36×10 -2 ) Peptococcaceae 3.13×10 protective factors DR. Genus- Ruminococcaceae_UCG_011 4.83×10 -3 ), genus- Eubacterium_rectale_group 3.44×10 Adlercreutzia 4.82×10 correlated with At phylum, class order levels, we found no causally related >0.05). Heterogeneity >0.05) pleiotropy analysis robustness results. Conclusion We there potential some DR, which highlights axis offered new insights into GM-mediated mechanism Further explorations required will lead find biomarkers targeted prevention strategies

Language: Английский

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The causality between intestinal flora and allergic diseases: Insights from a bi-directional two-sample Mendelian randomization analysis

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

Published: March 9, 2023

Background Growing evidence shows a significant association between intestinal flora and allergic diseases, specifically atopic dermatitis (AD), rhinitis (AR), asthma (AA). However, the causality has not yet been clarified. Objective We conducted bidirectional two-sample Mendelian randomization (TSMR) analysis to study causal relationships classification AD, AR, or AA. Materials methods obtained summary data of flora, AA from genome-wide research. The inverse-variance weighted method is primary for analyzing in TSMR analysis. Several sensitivity analyses were examine stability results. Reverse was also performed assess whether there reverse causality. Results A total 7 bacterial taxa associated with identified by current Specifically, genus Dialister( P =0.034)and Prevotella( =0.047)were higher risk whereas class Coriobacteriia ( =0.034) its child taxon, order Coriobacteriales family Coriobacteriaceae =0.034), all had protective effect on AR. In addition, Victivallaceae =0.019) as factor noticed positive Holdemanella =0.046) didn’t suggest any diseases flora. Conclusion confirmed relationship provided an innovative perspective research diseases: targeted regulation dysregulation specific prevent treat

Language: Английский

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A large-scale causal analysis of gut microbiota and delirium: A Mendelian randomization study

Journal of Affective Disorders, Journal Year: 2023, Volume and Issue: 329, P. 64 - 71

Published: Feb. 25, 2023

Several studies have linked gut microbiota to human brain activity. This study used Mendelian randomization (MR) investigate the causal relationship between microbes and delirium.MR was select SNPs from large-scale GWAS summary data on 211 taxa delirium. Inverse variance weighting (IVW), weighted median, MR-Egger methods were for statistical analyses. Outliers assessed using leave-one-out method. To avoid horizontal pleiotropy, we performed MR-PRESSO intercept tests. Cochran's Q I2 values IVW assess heterogeneity.IVW suggested that genetic prediction of family Desulfovibrionaceae (1.784 (1.267-2.512), P = 0.001), order Desulfovibrionales (1.501 (1.058-2.128), 0.023), genus Candidatus Soleaferrea (1.322 (1.052-1.659), 0.016) increased risk delirium, but Oxalobacteraceae (0.841 (0.722-0.981), 0.027), genera Holdemania (0.766 (0.620-0.946), 0.013), Ruminococcus gnavus (0.806 (0.661-0.982), 0.033), Eggerthella (0.815 (0.667-0.997), 0.047) reduced delirium.(1) Limited sample size, (2) inability interactions, (3) limited European populations.Our results suggest presence microbial Desulfovibrionaceae, Desulfovibrionales, whereas family, Holdemania, gnavus, decreased However, potential probiotic interventions in prevention perioperative delirium should be emphasized.

Language: Английский

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Association Between Sleep Traits and Rheumatoid Arthritis: A Mendelian Randomization Study

Frontiers in Public Health, Journal Year: 2022, Volume and Issue: 10

Published: June 30, 2022

Currently, the causal association between sleep disorders and rheumatoid arthritis (RA) has been poorly understood. In this two-sample Mendelian randomization (TSMR) study, we tried to explore whether are causally associated with RA. Seven sleep-related traits were chosen from published Genome-Wide Association Study (GWAS): short duration, frequent insomnia, any getting up, morningness (early-to-bed/up habit), snoring, 27, 53, 57, 70, 274, 42 individual single-nucleotide polymorphisms (SNPs) (P < 5 × 10-8) obtained as instrumental variables (IVs) for these traits. Outcome a public GWAS study that included 14,361 cases 43,923 European Ancestry controls. The relationship disturbances RA risk evaluated by (MR) analysis using inverse variance weighted (IVW), MR-Egger regression, median, weight mode methods. Regression pleiotropy residual sum outlier (MR-PRESSO) used test horizontal pleomorphism outliers. There was no evidence of link insomnia (IVW, odds ratio (OR): 0.99; 95% interval (CI): 0.84-1.16; P = 0.858), OR: 1.09; CI: 0.85-1.42; 0.489), duration 0.65, 0.38-1.10, 0.269), up 0.56, 0.13-2.46, 0.442), 2.59; 0.73-9.16; 0.142), or snoring 0.95; 0.68-1.33; 0.757). Short (6h) had effect on RA, supported IVW median (OR: 1.47, 1.12-1.94, 0.006; 1.43, 95%CI:1.01-2.05, 0.047). Sensitivity showed results stable. Our findings imply is linked an increased Therefore, length should be considered in disease models, physicians advise people avoid practices lower

Language: Английский

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Assessing the relationship between gut microbiota and irritable bowel syndrome: a two-sample Mendelian randomization analysis

BMC Gastroenterology, Journal Year: 2023, Volume and Issue: 23(1)

Published: May 12, 2023

Abstract Background Growing evidence has suggested that gut microbiota is closely related to the risk of irritable bowel syndrome (IBS), but whether there a causal effect remains unknown. We adopted Mendelian randomization (MR) approach evaluate potential relationships between and IBS. Methods Genetic instrumental variables for were identified from genome-wide association study (GWAS) 18,340 participants. Summary statistics IBS drawn GWAS including 53,400 cases 433,201 controls. used inverse-variance weighted (IVW) method as primary analysis. To test robustness our results, we further performed weighted-median method, MR-Egger regression, MR pleiotropy residual sum outlier test. Finally, reverse analysis was possibility causation. Results suggestive associations three bacterial traits (odds ratio (OR): 1.08; 95% confidence interval (CI): 1.02, 1.15; p = 0.011 phylum Actinobacteria; OR: 0.95; CI: 0.91, 1.00; 0.030 genus Eisenbergiella 1.10; 1.03, 1.18; 0.005 Flavonifractor ). The results sensitivity analyses these consistent. did not find statistically significant in Conclusions Our systematic provide support relationship several taxa More studies are required show how affects development

Language: Английский

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Association between biological aging and lung cancer risk: Cohort study and Mendelian randomization analysis

iScience, Journal Year: 2023, Volume and Issue: 26(3), P. 106018 - 106018

Published: Jan. 19, 2023

Chronological age only represents the passage of time, whereas biological reflects physiology states and susceptibility to morbidity mortality. The association between lung cancer risk remains controversial. Hence, we conducted a prospective analysis in UK Biobank study two-sample Mendelian randomization investigate this association. Biological aging was evaluated by PhenoAgeAccel, derived from routine clinical biomarkers. Independent chronological age, PhenoAgeAccel positively associated with overall histological subtypes cancer. There joint effect genetics incidence. In analysis, genetically predicted increased cancer, small cell, squamous cell carcinoma. Our findings suggest is an independent factor for which could be incorporated polygenic score identify high-risk individuals

Language: Английский

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Causal effects between gut microbiota and IgA nephropathy: a bidirectional Mendelian randomization study

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

Published: May 2, 2023

Therapeutic approaches that target the gut microbiota (GM) may be helpful in potential prevention and treatment of IgA nephropathy (IgAN). Meanwhile, relevant studies demonstrated a correlation between GM IgAN, however, these confounding evidence cannot prove causal relationship IgAN.Based on data from genome-wide association study (GWAS) MiBioGen IgAN GWAS FinnGen research. A bi-directional Mendelian randomization (MR) was performed to explore IgAN. We used inverse variance weighted (IVW) method as primary determine exposure outcome our MR study. Besides, we additional analysis (MR-Egger, median) sensitivity (Cochrane's Q test, MR-Egger MR-PRESSO) select significant results, followed by Bayesian model averaging (MR-BMA) test results Finally, reverse conducted estimate probability causality.At locus-wide significance level, IVW showed Genus Enterorhabdus protective factor for [OR: 0.456, 95% CI: 0.238-0.875, p=0.023], while butyricicoccus risk 3.471, 1.671-7.209, p=0.0008]. In analysis, no pleiotropy or heterogeneity found.Our revealed expanded variety bacterial taxa causally related These could become novel biomarkers facilitate development targeted therapies developing understanding "gut-kidney axis".

Language: Английский

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Assessing causal relationships between gut microbiota and asthma: evidence from two sample Mendelian randomization analysis

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

Published: July 19, 2023

Background Accumulating evidence has suggested that gut microbiota dysbiosis is commonly observed in asthmatics. However, it remains unclear whether a cause or consequence of asthma. We aimed to examine the genetic causal relationships with asthma and its three phenotypes, including adult-onset asthma, childhood-onset moderate-severe Methods To elucidate causality we applied two sample Mendelian randomization (MR) based on largest publicly available genome-wide association study (GWAS) summary statistics. Inverse variance weighting meta-analysis (IVW) was used obtain main estimates; Weighted median, MR-Egger, Robust Adjusted Profile Score (MR-RAPS), Maximum likelihood method (ML), MR pleiotropy residual sum outlier (MR-PRESSO) methods were sensitivity analyses. Finally, reverse analysis performed evaluate possibility causation. Results In absence heterogeneity horizontal pleiotropy, IVW revealed genetically predicted Barnesiella RuminococcaceaeUCG014 positively correlated risk while between CandidatusSoleaferrea negative. And for phenotypes Akkermansia reduced Collinsella increased FamilyXIIIAD3011group , Eisenbergiella Ruminiclostridium6 (all P &lt;0.05). The didn’t find supporting from genus. Conclusion This microbial genera causally associated as well phenotypes. findings deepened our understanding role pathology which emphasizes potential opening up new vista prevention diagnosis

Language: Английский

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