Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis
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PROVIDER: S-EPMC10982360 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Background: Glioblastoma (GBM) is the most prevalent malignant brain tumor, significantly impacting the physical and mental wellbeing of patients. Several studies have demonstrated a close association between gut microbiota and the development of GBM. In this investigation, Mendelian randomization (MR) was employed to rigorously evaluate the potential causal relationship between gut microbiota and GBM. Methods: We utilized summary statistics derived from genome-wide association studies (GWAS) encompassing 211 gut microbiota and GBM. The causal association between gut microbiota and GBM was scrutinized using Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods. Cochrane's Q statistic was employed to conduct a heterogeneity test. MR-Pleiotropic Residuals and Outliers (MR-PRESSO) were applied to identify and eliminate SNPs with horizontal pleiotropic outliers. Additionally, Reverse MR was employed to assess the causal relationship between GBM and pertinent gut microbiota. Results: The MR study estimates suggest that the nine gut microbiota remain stable, considering heterogeneity and sensitivity methods. Among these, the family.Peptostreptococcaceae and genus.Eubacterium brachy group were associated with an increased risk of GBM, whereas family.Ruminococcaceae, genus.Anaerostipes, genus.Faecalibacterium, genus.LachnospiraceaeUCG004, genus.Phascolarctobacterium, genus.Prevotella7, and genus.Streptococcus were associated with a reduced risk of GBM. Following Benjamini and Hochberg (BH) correction, family.Ruminococcaceae (OR = 0.04, 95% CI: 0.01-0.19, FDR = 0.003) was identified as playing a protective role against GBM. Conclusion: This groundbreaking study is the first to demonstrate that family.Ruminococcaceae is significantly associated with a reduced risk of GBM. The modulation of family_Ruminococcaceae for the treatment of GBM holds considerable potential clinical significance.
| S-EPMC10794655 | biostudies-literature
Project description:BackgroundThere have been previously reported associations between the gut microbiota, immune cells, and colorectal cancer; however, the specific mechanisms underlying these relationships remain largely unexplored and require further research. Therefore, in this study, we aimed to unravel the interactions between the gut microbiota, immune cells, and colorectal cancer.MethodsThe analysis used genome-wide association study (GWAS) data encompassing 207 microbial taxa and 205 functional pathways and data on 731 immune cell phenotypes. Colorectal cancer data on 6 581 cases and 463 421 controls were sourced from the Integrative Epidemiology Unit Open GWAS Project. Univariate inverse-variance weighted Mendelian randomization analysis was used to identify gut microbial taxa associated with colorectal cancer. Mediation analysis was used to identify the mediating role of specific immune cells in the link between gut bacteria and colorectal cancer.ResultsUnivariate inverse-variance weighted Mendelian randomization analysis revealed that several microbial taxa from the Actinobacteria and Firmicutes phyla were significantly associated with colorectal cancer. Coriobacteriaceae (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.72-0.97), Sutterellaceae (OR: 0.88, 95% CI: 0.78-0.99), Eggerthella (OR: 0.91, 95% CI: 0.84-0.99), Coriobacteriales (OR: 0.84, 95% CI: 0.72-0.97), Collinsella aerofaciens (OR: 0.85, 95% CI: 0.74-0.99), and Ruminococcus bromii (OR: 0.91, 95% CI: 0.83-0.99) were negatively associated with colorectal cancer, whereas Lactobacillales (OR: 1.11, 95% CI: 1.03-1.20), Veillonella (OR: 1.08, 95% CI: 1.01-1.15), and Bifidobacterium bifidum (OR: 1.05, 95% CI: 1.00-1.09) were positively associated with colorectal cancer. Mediation analysis revealed that in the causal pathway from Collinsella aerofaciens to colorectal cancer, CD127 on CD28+ CD45RA- CD8br and human leukocyte antigen (HLA) DR on CD33- HLA DR+, mediated 11.30% and - 6.52% of the effect, respectively, and that in the causal pathway from Ruminococcus bromii to colorectal cancer, IgD- CD38dim %lymphocyte mediated - 14.80% of the effect.ConclusionsThese results highlight the potential of gut microbiota and immune cell phenotypes as novel treatment strategies for colorectal cancer.
| S-EPMC11881383 | biostudies-literature
Project description:BackgroundRecent studies have suggested a potential correlation between ecological dysregulation of the gut microbiota (GM) and the onset and development of postpartum depression (PPD). In addition, inflammatory factors (IFs) have been reported to play an important role in the development of PPD. However, the causal connections among GM, IFs, and PPD remain to be understood.ObjectiveThis study sought to determine if genetically predicted GM and IFs exert a causal effect on PPD and to study whether IFs mediate the causal effect of GM on PPD.MethodsTwo-step and two-sample Mendelian randomization (MR) analyses, primarily employing the inverse variance weighted (IVW) method, were conducted to evaluate the causal relationship between GM, IFs, and PPD, and to assess potential mediating effects. Heterogeneity and horizontal pleiotropy tests were performed to evaluate the robustness of the findings and the strength of the causal associations.ResultsClass Alphaproteobacteria, genus Family XIII AD3011 group exhibited a positive association with PPD risk; whereas, the family Clostridiales vadin BB60 group, family Veillonellaceae, genus Ruminococcaceae UCG011, and the inflammatory factors C-C motif chemokine ligand 5 (CCL5) and C-C motif chemokine ligand 3 (CCL3) demonstrated negative correlations with PPD risk. IFs did not exhibit a mediating role. No heterogeneity or horizontal pleiotropy was observed.ConclusionsOur MR study offered genetic evidence that GM and IFs contribute to the pathogenesis of PPD, with no mediating effect of IFs. This enhances our understanding of PPD's pathological mechanisms and offers new perspectives for developing novel preventative and therapeutic strategies.
| S-EPMC11834640 | biostudies-literature
Project description:BackgroundAn increasing number of studies have revealed that gut microbiota influences the development and progression of Colorectal cancer (CRC). However, whether a causal relationship exists between the two remains unclear, and the role of immune cells in this context is not well understood.ObjectiveTo elucidate the causal relationship between gut microbiota and CRC and to explore the potential mediating role of circulating immune cells.Materials and methodsTo analyze the causal relationship between gut microbiota and CRC, we employed a univariable Mendelian randomization (UVMR) approach. Subsequently, a two-step multivariable Mendelian randomization (MVMR) to assess the potential mediating role of circulating immune cells. Primarily, applied the Inverse-Variance Weighted method to evaluate the causal relationship between exposure and outcome. To ensure the robustness of the results linking gut microbiota and CRC, we validated the findings using Robust Inverse-Variance Weighted, Penalized Inverse-Variance Weighted, and Penalized Robust Inverse-Variance Weighted methods. Additionally, we employed MR-Egger Intercept to mitigate the influence of horizontal pleiotropy. MR-PRESSO was used to detect and correct outliers by excluding anomalous instrumental variables. Finally, we supplemented our analysis with methods such as Bayesian Weighted Mendelian Randomization (BWMR), Maximum-Likelihood, Lasso, Debiased Inverse Variance Weighted, and Contamination Mixture to establish a robust and compelling causal relationship.ResultsAfter accounting for reverse causality, horizontal pleiotropy, and various methodological corrections, Bifidobacterium kashiwanohense, GCA-900066755 sp900066755, Geminocystis, and Saccharofermentanaceae exhibited strong and robust causal effects on CRC. Specifically, CD40 on monocytes (2.82%) and CD45 on CD33+HLA-DR+CD14- cells (12.87%) mediated the causal relationship between Bifidobacterium kashiwanohense and CRC risk. Furthermore, CD45 on CD33-HLA-DR+ (3.94%) mediated the causal relationship between GCA-900066755 sp900066755 and CRC risk. Additionally, terminally differentiated CD4+T cells (11.55%) mediated the causal relationship between Geminocystis and CRC risk. Lastly, CD40 on monocytes (2.35%), central memory CD4+T cells (5.76%), and CD28 on CD28+CD45RA+CD8+T cells (5.00%) mediated the causal relationship between Saccharofermentanaceae and CRC risk.ConclusionOur mediation MR analysis provides genetic evidence suggesting that circulating immune cells may mediate the causal relationship between gut microbiota and CRC. The identified associations and mediation effects offer new insights into potential therapeutic avenues for CRC.
| S-EPMC11825486 | biostudies-literature
Project description:Emerging research underscores the substantial link between gut flora and various inflammatory skin diseases. We hypothesize that there exists a complex gut-skin axis, possibly affecting the progression of conditions such as eczema, acne, psoriasis, and rosacea. However, the precise nature of the causal connection between gut flora and skin diseases remains unestablished. In this study, we started by compiling summary data from genome-wide association studies (GWAS) featuring 211 unique gut microbiota and four types of skin conditions. We scrutinized these data across different taxonomic strata. Subsequently, we leveraged Mendelian randomization (MR) to ascertain if there is a causal link between gut microbiota and these skin conditions. We also performed a bidirectional MR analysis to identify the causality's direction. By utilizing Mendelian randomization, we identified 26 causal connections between the gut microbiome and four recognized inflammatory skin conditions, including 9 positive and 17 negative causal directions. Additional sensitivity analyses of these results revealed no evidence of pleiotropy or heterogeneity. Our MR analysis suggests a causal connection between gut microbiota and skin diseases, potentially providing groundbreaking perspectives for future mechanistic and clinical studies on microbiota-affected skin conditions.
| S-EPMC10609507 | biostudies-literature
Project description:BackgroundThe correlation between diabetic nephropathy (DN) and gut microbiota (GM) has been suggested in numerous animal experiments and cross-sectional studies. However, a causal association between GM and DN has not been ascertained.MethodsThis research adopted MR analysis to evaluate the causal link between GM and DN derived from data acquired through publicly available genome-wide association studies (GWAS). The study utilized the inverse variance weighted (IVW) approach to assess causal association between GM and DN. Four additional methods including MR-Egger, weighted median, weighted mode, and simple mode were employed to ensure comprehensive analysis and robust results. The Cochran's Q test and the MR-Egger method were conducted to identify heterogeneity and horizontal pleiotropy, respectively. The leave-one-out approach was utilized to evaluate the stability of MR results. Finally, a reverse MR was performed to identify the reverse causal association between GM and DN.ResultsAccording to IVW analysis, Class Verrucomicrobiae (p = 0.003), Order Verrucomicrobiales (p = 0.003), Family Verrucomicrobiaceae (p = 0.003), Genus Akkermansia (p = 0.003), Genus Catenibacterium (p = 0.031), Genus Coprococcus 1 (p = 0.022), Genus Eubacterium hallii group (p = 0.018), and Genus Marvinbryantia (p = 0.023) were associated with a higher risk of DN. On the contrary, Class Actinobacteria (p = 0.037), Group Eubacterium ventriosum group (p = 0.030), Group Ruminococcus gauvreauii group (p = 0.048), Order Lactobacillales (p = 0.045), Phylum Proteobacteria (p = 0.017) were associated with a lower risk of DN. The sensitivity analysis did not identify any substantial pleiotropy or heterogeneity in the outcomes. We found causal effects of DN on 11 GM species in the reverse MR analysis. Notably, Phylum Proteobacteria and DN are mutually causalities.ConclusionThis study identified the causal association between GM and DN with MR analysis, which may enhance the understanding of the intestinal-renal axis and provide novel potential targets for early non-invasive diagnosis and treatment of DN.
| S-EPMC11004376 | biostudies-literature
Project description:BackgroundFibromyalgia (FM) is a syndrome characterized by chronic and widespread musculoskeletal pain. A number of studies have implied a potential association between gut microbiota and FM. However, the casual association between gut microbiota and FM remains unknown.MethodMendelian randomization (MR) study was conducted using the summary statistics of genetic variants from the genome-wide association study (GWAS). Inverse variance weighted (IVW), combined with MR-Egger and weighted median were used to investigate the causal association between 119 gut microbiota genera and FM. Sensitivity analyses were performed on the MR results, including heterogeneity test, leave-one-out test and pleiotropy test.ResultsA total of 1,295 single nucleotide polymorphism (SNPs) were selected as instrumental variables (IVs), with no significant heterogeneity and pleiotropy according to the sensitivity analyses. Five gut microbiota genera were found to have significant casual association with FM. Coprococcus2 (OR = 2.317, p-value = 0.005, 95% CI: 1.289-4.167), Eggerthella (OR = 1.897, p-value = 0.001, 95% CI: 1.313-2.741) and Lactobacillus (OR = 1.576, p-value =0.020, 95% CI: 1.073-2.315) can increase the risk of FM. FamillyXIIIUCG001 (OR = 0.528, p-value = 0.038, 95% CI: 0.289-0.964) and Olsenella (OR = 0.747, p-value = 0.050, 95% CI: 0.557-1.000) can decrease the risk of FM.ConclusionThis MR study found that gut microbiota is casually associated with FM. New insights into the mechanisms of FM mediated by gut microbiota are provided.
| S-EPMC10800605 | biostudies-literature
Project description:BackgroundSeveral recent studies speculated that the gut microbiota is associated with sensorineural hearing loss (SNHL) and proposed the concept of the gut-inner ear axis. However, the causal effect of gut microbiota on SNHL is still unknown. In this study, we performed a two-sample Mendelian randomization (MR) analysis to estimate the causal effect of gut microbiota on SNHL.MethodsGut microbiota data were obtained from the largest available genome-wide association study (n = 18,340) conducted by the MiBioGen consortium. The summary statistics of SNHL were obtained from the FinnGen consortium R8 release data (28,310 cases and 302,750 controls). The causal effects were estimated with inverse-variance weighted, MR-Egger, and weighted median. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be associated with SNHL in forward Mendelian randomization analysis. We then performed sensitivity analyses, including Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, cML-MA-BIC, and leave-one-out analysis, to detect heterogeneity and pleiotropy.ResultsThe inverse-variance weighted results suggested that Lachnospiraceae (UCG001) had a significant protective effect against SNHL (odds ratio = 0.85, 95% confidence interval: 0.78-0.93, P = 6.99 × 10-4). In addition, Intestinimonas (odds ratio = 0.89, 95% confidence interval: 0.82-0.97, P = 8.53 × 10-3) presented a suggestively protective effect on SNHL. Rikenellaceae (RC9gutgroup) (odds ratio = 1.08, 95% confidence interval: 1.02-1.15, P = 0.01) and Eubacterium (hallii group) (odds ratio = 1.12, 95% confidence interval: 1.00-1.24, P = 0.048) suggestively increase the risk of SNHL. The results of the reverse MR analysis showed that there is no significant causal effect of SNHL on the gut microbiota. No significant heterogeneity of instrumental variables or pleiotropy was detected.ConclusionThe evidence that the four genera mentioned above are associated with SNHL supports the hypothesis of a gut-inner ear axis. Our study provides microbial markers for the prevention and treatment of SNHL, and further studies are needed to explore the mechanisms of the gut microbiome-inner ear axis in health and diseases.
| S-EPMC10616596 | biostudies-literature
Project description:BackgroundRecent studies have shown that an imbalance in gut microbiota (GM) may not always be associated with endometriosis (EMS). To investigate this further, we conducted a two-sample Mendelian randomization study.MethodsMR analysis was performed on genome-wide association study (GWAS) summary statistics of GM and EMS. Specifically, the MiBioGen microbiota GWAS (N = 18,340) was used as exposure. The FinnGen study GWAS (8,288 EMS cases and 68,969 controls) was used as outcome. We primarily used the inverse variance weighted (IVW) method to analyze the correlation and conducted a sensitivity analysis to verify its reliability.Results(1) MR analysis: The results of the IVW method confirmed that a total of 8 GM taxa were related to the risk of EMS. Class-Melainabacteria (p = 0.036), family-Ruminococcaceae (p = 0.037), and genus-Eubacteriumruminantium (p = 0.015) had a protective effect on EMS, whereas order-Bacillales (p = 0.046), family-Prevotellaceae (p = 0.027), genus-Anaerotruncus (p = 0.025), genus-Olsenella (p = 0.036) and genus-RuminococcaceaeUCG002 (p = 0.035) could increase the risk of EMS. (2) Sensitivity analysis: Cochrane's Q test (p > 0.05), MR-Egger intercept method (p > 0.05), and leave-one-out method confirmed the robustness of MR results.ConclusionThis study performed a MR analysis on two large national databases and identified the association between 8 GM taxa and EMS. These taxa could potentially be utilized for indirectly diagnosing EMS and could lead to novel perspectives in research regarding the pathogenesis, diagnosis, and treatment of EMS.
| S-EPMC10565803 | biostudies-literature
Project description:BackgroundObservational studies have shown that gut microbiota is closely associated with inflammatory dermatoses such as psoriasis, rosacea, and atopic dermatitis (AD). However, the causal relationship between gut microbiota and inflammatory dermatosis remains unclear.MethodsBased on Maximum Likelihood (ML), MR-Egger regression, Inverse Variance Weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Weighted Mode, and Weighted Median Estimator (WME) methods, we performed a bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal relationship between gut microbiota and inflammatory dermatosis. The genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of inflammatory dermatosis (including psoriasis, AD, rosacea, vitiligo, acne, and eczema) came from the FinnGen consortium and IEU Open GWAS project. Cochran's IVW Q test tested the heterogeneity among instrumental variables (IVs). The horizontal pleiotropy was tested by MR-Egger regression intercept analysis and MR-PRESSO analysis.ResultsEventually, the results indicated that 5, 16, 17, 11, 15, and 12 gut microbiota had significant causal effects on psoriasis, rosacea, AD, vitiligo, acne, and eczema, respectively, including 42 protective and 34 risk causal relationships. Especially, Lactobacilli and Bifidobacteria at the Family and Genus Level, as common probiotics, were identified as protective factors for the corresponding inflammatory dermatoses. The results of reverse MR analysis suggested a bidirectional causal effect between AD and genus Eubacterium brachy group, vitiligo and genus Ruminococcaceae UCG004. The causal relationship between gut microbiota and psoriasis, rosacea, acne, and eczema is unidirectional. There was no significant heterogeneity among these IVs. In conclusion, this bidirectional two-sample MR study identified 76 causal relationships between the gut microbiome and six inflammatory dermatoses, which may be helpful for the clinical prevention and treatment of inflammatory dermatoses.
| S-EPMC10565349 | biostudies-literature