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

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.

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. 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.

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 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.

This 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.