AUTHOR=Sun Kewang , Gao Yan , Wu Huaqing , Huang Xiangyan 

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

JOURNAL=Frontiers in Public Health

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2023.1255059

DOI=10.3389/fpubh.2023.1255059

ISSN=2296-2565

ABSTRACT=Background: Type 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. Methods: The 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. TheInverse Variance Weighted(IVW), Simple mode, MR-Egger, Weighted Median and Weighted Mode 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. Results: The 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 T2DM. False Discovery Rate correction was performed with finding that genus.Allisonella, genus.Alistipes, family Coriobacteriaceae and T2DM no longer displayed a significant causal This is a provisional file, not the final typeset article association . In addition, no significant heterogeneity or horizontal pleiotropy was found for instrumental variable. Conclusion:This mendelian randomized study relies on genetic variation tools to confirm the causal relationship between the presence of genus Flavonifractor, genus Haemophilus, family Clostridiaceae1, genus Actinomyces and genus Candidatus Soleaferrea in the gut and T2DM , providing new directions and strategies for the treatment and early screening of T2DM , which carries clinical significance.