The causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomized study

BackgroundType 2 diabetes mellitus (T2DM) is a commonly observed metabolic anomaly globally, and as of the present time, there's no recognized solution. There is an increasing body of evidence from numerous observational studies indicating a significant correlation between gut flora and metabol...

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Main Authors: Kewang Sun, Yan Gao, Huaqing Wu, Xiangyan Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-09-01
Series:Frontiers in Public Health
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2023.1255059/full
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author Kewang Sun
Kewang Sun
Yan Gao
Huaqing Wu
Xiangyan Huang
author_facet Kewang Sun
Kewang Sun
Yan Gao
Huaqing Wu
Xiangyan Huang
author_sort Kewang Sun
collection DOAJ
description BackgroundType 2 diabetes mellitus (T2DM) is a commonly observed metabolic anomaly globally, and as of the present time, there's no recognized solution. There is an increasing body of evidence from numerous observational studies indicating a significant correlation between gut flora and metabolic disease progression, particularly in relation to T2DM. Despite this, the direct impact of gut microbiota on T2DM isn't fully understood yet.MethodsThe summary statistical figures for intestinal microbiota were sourced from the MiBioGen consortium, while the summary statistical data for T2DM were gathered from the Genome-Wide Association Studies (GWAS) database. These datasets were used to execute a two-sample Mendelian randomization (MR) investigation. The Inverse Variance Weighted (IVW), Maximum Likelihood, MR-Egger, Weighted Median, and Weighted Models strategies were employed to assess the impact of gut microbiota on T2DM. Findings were primarily obtained using the IVW technique. Techniques like MR-Egger were employed to identify the occurrence of horizontal pleiotropy among instrumental variables. Meanwhile, Cochran's Q statistical measures were utilized to assess the variability or heterogeneity within these instrumental variables.ResultsThe outcomes from the IVW analysis demonstrated that the genus Alistipes (OR = 0.998, 95% confidence interval: 0.996–1.000, and P = 0.038), genus Allisonella (OR = 0.998, 95% confidence interval: 0.997-0.999, P = 0.033), genus Flavonifractor (OR = 0.995, 95% confidence interval: 0.993–0.998, P = 3.78 × 10−3), and genus Haemophilus (OR = 0.995, 95% confidence interval: 0.993–0.998, P = 8.08 × 10−3) all acted as defense elements against type 2 diabetes. Family Clostridiaceae1 (OR = 1.003, 95% confidence interval: 1.001–1.005, P = 0.012), family Coriobacteriaceae (OR = 1.0025, 95% confidence interval: 1.000–1.005, P = 0.043), genus Actinomyces (OR = 1.003,95% confidence interval: 1.001–1.005, P = 4.38 × 10−3), genus Candidatus Soleaferrea (OR = 1.001,95% confidence interval: 1.000–1.002 P = 0.012) were risk factors for type 2 diabetes. False Discovery Rate correction was performed with finding that genus.Allisonella, genus.Alistipes, family Coriobacteriaceaeand T2DM no longer displayed a significant causal association. In addition, no significant heterogeneity or horizontal pleiotropy was found for instrumental variable.ConclusionThis MR study relies on genetic variation tools to confirm the causal effect of genus Flavonifractor, genus Haemophilus, family Clostridiaceae1, genus Actinomyces and genus Candidatus Soleaferrea on T2DM in the gut microbiome, providing new directions and strategies for the treatment and early screening of T2DM, which carries significant clinical relevance. To develop new biomarkers and better understand targeted prevention strategies for T2DM, further comprehensive investigations are required into the protective and detrimental mechanisms exerted by these five genera against T2DM.
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spelling doaj.art-2cc8baa1294c4968a1daeef956e6497e2023-09-22T10:36:07ZengFrontiers Media S.A.Frontiers in Public Health2296-25652023-09-011110.3389/fpubh.2023.12550591255059The causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomized studyKewang Sun0Kewang Sun1Yan Gao2Huaqing Wu3Xiangyan Huang4School of Medical Laboratory, Weifang Medical College, Weifang, ChinaDepartment of Blood Transfusion, The 960th Hospital of the PLA Jonit Logistics Support Force, Jinan, ChinaDepartment of General Medicine, The 960th Hospital of the PLA Jonit Logistics Support Force, Jinan, ChinaSchool of Mathematics and Statistics, Beijing Technology and Business University, Beijing, ChinaDepartment of Blood Transfusion, The 960th Hospital of the PLA Jonit Logistics Support Force, Jinan, ChinaBackgroundType 2 diabetes mellitus (T2DM) is a commonly observed metabolic anomaly globally, and as of the present time, there's no recognized solution. There is an increasing body of evidence from numerous observational studies indicating a significant correlation between gut flora and metabolic disease progression, particularly in relation to T2DM. Despite this, the direct impact of gut microbiota on T2DM isn't fully understood yet.MethodsThe summary statistical figures for intestinal microbiota were sourced from the MiBioGen consortium, while the summary statistical data for T2DM were gathered from the Genome-Wide Association Studies (GWAS) database. These datasets were used to execute a two-sample Mendelian randomization (MR) investigation. The Inverse Variance Weighted (IVW), Maximum Likelihood, MR-Egger, Weighted Median, and Weighted Models strategies were employed to assess the impact of gut microbiota on T2DM. Findings were primarily obtained using the IVW technique. Techniques like MR-Egger were employed to identify the occurrence of horizontal pleiotropy among instrumental variables. Meanwhile, Cochran's Q statistical measures were utilized to assess the variability or heterogeneity within these instrumental variables.ResultsThe outcomes from the IVW analysis demonstrated that the genus Alistipes (OR = 0.998, 95% confidence interval: 0.996–1.000, and P = 0.038), genus Allisonella (OR = 0.998, 95% confidence interval: 0.997-0.999, P = 0.033), genus Flavonifractor (OR = 0.995, 95% confidence interval: 0.993–0.998, P = 3.78 × 10−3), and genus Haemophilus (OR = 0.995, 95% confidence interval: 0.993–0.998, P = 8.08 × 10−3) all acted as defense elements against type 2 diabetes. Family Clostridiaceae1 (OR = 1.003, 95% confidence interval: 1.001–1.005, P = 0.012), family Coriobacteriaceae (OR = 1.0025, 95% confidence interval: 1.000–1.005, P = 0.043), genus Actinomyces (OR = 1.003,95% confidence interval: 1.001–1.005, P = 4.38 × 10−3), genus Candidatus Soleaferrea (OR = 1.001,95% confidence interval: 1.000–1.002 P = 0.012) were risk factors for type 2 diabetes. False Discovery Rate correction was performed with finding that genus.Allisonella, genus.Alistipes, family Coriobacteriaceaeand T2DM no longer displayed a significant causal association. In addition, no significant heterogeneity or horizontal pleiotropy was found for instrumental variable.ConclusionThis MR study relies on genetic variation tools to confirm the causal effect of genus Flavonifractor, genus Haemophilus, family Clostridiaceae1, genus Actinomyces and genus Candidatus Soleaferrea on T2DM in the gut microbiome, providing new directions and strategies for the treatment and early screening of T2DM, which carries significant clinical relevance. To develop new biomarkers and better understand targeted prevention strategies for T2DM, further comprehensive investigations are required into the protective and detrimental mechanisms exerted by these five genera against T2DM.https://www.frontiersin.org/articles/10.3389/fpubh.2023.1255059/fullMendelian randomized studygut microbiotatype 2 diabetescausal inferencegenetic variation
spellingShingle Kewang Sun
Kewang Sun
Yan Gao
Huaqing Wu
Xiangyan Huang
The causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomized study
Frontiers in Public Health
Mendelian randomized study
gut microbiota
type 2 diabetes
causal inference
genetic variation
title The causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomized study
title_full The causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomized study
title_fullStr The causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomized study
title_full_unstemmed The causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomized study
title_short The causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomized study
title_sort causal relationship between gut microbiota and type 2 diabetes a two sample mendelian randomized study
topic Mendelian randomized study
gut microbiota
type 2 diabetes
causal inference
genetic variation
url https://www.frontiersin.org/articles/10.3389/fpubh.2023.1255059/full
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