Dataset Information

Causal relationship between gut microbiota and gastric cancer: A two‑sample Mendelian randomization analysis.

ABSTRACT: The gut microbiota is associated with GC; however, the causal association between the gut microbiota and GC remains to be determined. The aim of the present study was to investigate the causal association between gut microbiota and gastric cancer (GC) from the perspective of Mendelian randomization (MR). The present study performed MR analysis using summary statistics from a genome-wide association study of the gut microbiome and GC. Inverse-variance weighted, MR-Egger and weighted median methods were used to investigate the causal relationship between gut microbiota and GC. Heterogeneity tests were performed using Cochrane's Q statistic. Horizontal polytropy was detected using Mendelian Randomization Pleiotropy RESidual Sum and Outlier were eliminated. Estimates from MR indicated that nine gut microorganism remained stable with regard to acceptance of heterogeneity and sensitivity methods. Among them, the genera Prevotella 7, Roseburia and Ruminococcaceae UCG014 were associated with an increased risk of GC; by contrast, the family Enterobacteriaceae, the genera Allisonella, Lachnospiraceae FCS020, Ruminococcaceae UCG004 and Ruminococcaceae UCG009, and the order Enterobacteriales decreased the risk of GC development. The present study demonstrated the potential importance of modulating the abundance of gut microbiota for the prevention and treatment of GC.

SUBMITTER: Zhang J

PROVIDER: S-EPMC11019462 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature

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Causal relationship between gut microbiota and gastric cancer: A two‑sample Mendelian randomization analysis.

Zhang Jianling J Dong Chunlu C Lin Yanyan Y Shang Lifeng L Ma Junming J Hu Ruiping R Wang Hejing H

Molecular and clinical oncology 20240402 5

The gut microbiota is associated with GC; however, the causal association between the gut microbiota and GC remains to be determined. The aim of the present study was to investigate the causal association between gut microbiota and gastric cancer (GC) from the perspective of Mendelian randomization (MR). The present study performed MR analysis using summary statistics from a genome-wide association study of the gut microbiome and GC. Inverse-variance weighted, MR-Egger and weighted median method ...[more]

PMID: 38628559

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Project description:ObjectiveEmerging evidence has provided compelling evidence linking gut microbiota (GM) and diabetic nephropathy (DN) via the "gut-kidney" axis. But the causal relationship between them hasn't been clarified yet. We perform a Two-Sample Mendelian randomization (MR) analysis to reveal the causal connection with GM and the development of DN, type 1 diabetes nephropathy (T1DN), type 2 diabetes nephropathy (T2DN), type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM).MethodsWe used summary data from MiBioGen on 211 GM taxa in 18340 participants. Generalized MR analysis methods were conducted to estimate their causality on risk of DN, T1DN, T2DN, T1DM and T2DM from FinnGen. To ensure the reliability of the findings, a comprehensive set of sensitivity analyses were conducted to confirm the resilience and consistency of the results.ResultsIt was showed that Class Verrucomicrobiae [odds ratio (OR) =1.5651, 95%CI:1.1810-2.0742,PFDR=0.0018], Order Verrucomicrobiales (OR=1.5651, 95%CI: 1.1810-2.0742, PFDR=0.0018) and Family Verrucomicrobiaceae (OR=1.3956, 95%CI:1.0336-1.8844, PFDR=0.0296) had significant risk of DN. Our analysis found significant associations between GM and T2DN, including Class Verrucomimicrobiae (OR=1.8227, 95% CI: 1.2414-2.6763, PFDR=0.0139), Order Verrucomimicrobiae (OR=1.5651, 95% CI: 1.8227-2.6764, PFDR=0.0024), Rhodospirillales (OR=1.8226, 95% CI: 1.2412-2.6763, PFDR=0.0026), and Family Verrucomicroniaceae (OR=1.8226, 95% CI: 1.2412-2.6763, PFDR=0.0083). The Eubacteriumprotogenes (OR=0.4076, 95% CI: 0.2415-0.6882, PFDR=0.0021) exhibited a protection against T1DN. Sensitivity analyses confirmed that there was no significant heterogeneity and pleiotropy.ConclusionsAt the gene prediction level, we identified the specific GM that is causally linked to DN in both T1DM and T2DM patients. Moreover, we identified distinct microbial changes in T1DN that differed from those seen in T2DN, offering valuable insights into GM signatures associated with subtype of nephropathy.

Project description:BackgroundThe association between gut microbiota and leukemia has been established, but the causal relationship between the two remains unclear.MethodsA bidirectional two-sample Mendelian randomization (MR) was used to analyze the causal relationship between gut microbiota and leukemia. Microbiome data (n = 14,306) and leukemia (n = 1,145) data were both sourced from European populations. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on several criteria. We employed various MR methods, such as the inverse variance weighted (IVW) method, to evaluate the causal effect between exposure and outcomes and conducted sensitivity analyses to validate the heterogeneity and pleiotropy of the instrumental variables.Results5,742 qualified instrumental variables were included. In the primary MR results, a total of 10 gut microbial taxa were associated with leukemia risk. Genus Blautia and genus Lactococcus are risk factors for acute lymphoblastic leukemia [genus Blautia odds ratio (OR): 1.643, 95% confidence interval (CI): 1.592 ~ 1.695, Adjusted p < 0.001; genus Lactococcus OR: 2.152, 95% CI: 1.447 ~ 3.199, Adjusted p = 0.011]. Genus Rikenellaceae RC9 gut group, genus Anaerostipes, genus Slackia, and genus Lachnospiraceae ND3007 group are risk factors for acute myeloid leukemia [genus Rikenellaceae RC9 gut group OR: 1.964, 95% CI: 1.573 ~ 2.453, Adjusted p < 0.001; genus Anaerostipes OR: 2.515, 95% CI: 1.503 ~ 4.209, Adjusted p = 0.017; genus Slackia OR: 2.553, 95% CI: 1.481 ~ 4.401, Adjusted p = 0.022; genus Lachnospiraceae ND3007 group OR: 3.417, 95% CI: 1.960 ~ 5.959, Adjusted p = 0.001]. Genus Ruminococcaceae UCG011 and genus Ruminococcaceae UCG014 were risk factors for chronic myeloid leukemia (genus Ruminococcaceae UCG011 OR: 2.010, 95% CI: 1.363 ~ 2.963, Adjusted p = 0.044; genus Ruminococcaceae UCG014 OR: 3.101, 95% CI: 1.626 ~ 5.915, Adjusted p = 0.044). Genus Slackia was a protective factor for acute lymphoblastic leukemia (genus Slackia OR: 0.166, 95% CI: 0.062 ~ 0.443, Adjusted p = 0.017). Family Acidaminococcaceae was a protective factor for acute myeloid leukemia (family Acidaminococcaceae OR: 0.208, 95% CI: 0.120 ~ 0.361, Adjusted p < 0.001). Genus Desulfovibrio was a protective factor for chronic lymphoblastic leukemia (genus Desulfovibrio OR: 0.581, 95% CI: 0.440 ~ 0.768, Adjusted p = 0.020). Sensitivity analysis revealed no heterogeneity or pleiotropy between SNPs.ConclusionThis study revealed the causal relationship between the gut microbiota and leukemia, and identified potential pathogenic bacteria and probiotic taxa associated with the onset of leukemia. This research may aid in the early detection of various types of leukemia and offer a new direction for the prevention and treatment of leukemia.

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Project description:BackgroundAccumulating evidence suggests that alterations in gut microbiota composition are associated with the hidradenitis suppurativa (HS). However, the causal association between gut microbiota and HS remain undetermined.MethodsWe performed a bidirectional two-sample Mendelian randomization (MR) analysis using genome-wide association study summary data of gut microbiota and hidradenitis suppurativa from the MiBioGen consortium which concluded 18,340 individuals analyzed by the MiBioGen Consortium, comprising 211 gut microbiota. HS data were acquired from strictly defined HS data collected by FinnGenbiobank analysis, which included 211,548 European ancestors (409 HS patients, 211,139 controls). The inverse variance weighted method (IVW), weighted median (WME), simple model, weighted model, weighted median, and MR-Egger were used to determine the changes of HS pathogenic bacterial taxa, followed by sensitivity analysis including horizontal pleiotropy analysis. The MR Steiger test evaluated the strength of a causal association and the leave-one-out method assessed the reliability of the results. Additionally, a reverse MR analysis was carried out to seek for possible reverse causality.ResultsBy combining the findings of all the MR steps, we identified four causal bacterial taxa, namely, Family XI, Porphyromonadaceae, Clostridium innocuum group and Lachnospira. The risk of HS might be positively associated with a high relative abundance of Clostridium innocuum group (Odds ratio, OR 2.17, p = 0.00038) and Lachnospira (OR 2.45, p = 0.017) but negatively associated with Family XI (OR 0.67, p = 0.049) and Porphyromonadaceae (OR 0.29, p = 0.014). There were no noticeable outliers, horizontal pleiotropy, or heterogeneity. Furthermore, there was no proof of reverse causation found in the reverse MR study.ConclusionThis study indicates that Clostridium innocuum group and Lachnospira might have anti-protective effect on HS, whereas Family XI and Porphyromonadaceae might have a protective effect on HS. Our study reveals that there exists a beneficial or detrimental causal effect of gut microbiota composition on HS and offers potentially beneficial methods for therapy and avoidance of HS.

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Dataset Information

Causal relationship between gut microbiota and gastric cancer: A two‑sample Mendelian randomization analysis.

Publications

Causal relationship between gut microbiota and gastric cancer: A two‑sample Mendelian randomization analysis.

Similar Datasets

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