Gut microbiome links obesity to type 2 diabetes: insights from Mendelian randomization

Research has established links between the gut microbiome (GM) and both obesity and type 2 diabetes (T2D), which is much discussed, but underexplored. This study employed body mass index (BMI) as the measurement of obesity to delve deeper into the correlations from a genetic perspective.

We performed the Mendelian randomization (MR) analysis to examine the causal effects of GM on T2D and BMI, and vice versa. Genome-wide association study (GWAS) summary datasets were utilized for the analysis, including T2D (N = 933,970), BMI (N = 806,834), and two GM datasets from the international consortium MiBioGen (211 taxa, N = 18,340) and the Dutch Microbiome Project (DMP) (207 taxa, N = 7,738). These datasets mainly cover European populations, with additional cohorts from Asia and other regions. To further explore the potential mediating role of GM in the connections between BMI and T2D, their interaction patterns were summarized into a network.

MR analysis identified 9 taxa that showed protective properties against T2D. Seven species were within the Firmicutes and Bacteroidales phyla in the DMP, and two were from the MiBioGen (Odds Ratio (OR): 0.94-0.95). Conversely, genetic components contributing to the abundance of 12 taxa were associated with increased risks of T2D (OR: 1.04-1.12). Furthermore, T2D may elevate the abundance of seven taxa (OR: 1.03-1.08) and reduce the abundance of six taxa (OR: 0.93-0.97). In the analysis of the influence of the genetic component of BMI on GM composition, BMI affected 52 bacterial taxa, with 28 decreasing (OR: 0.75-0.92) and 24 increasing (OR: 1.08-1.27). Besides, abundances of 25 taxa were negatively correlated with BMI (OR: 0.95-0.99), while positive correlations were detected for 14 taxa (OR: 1.01-1.05). Notably, we uncovered 11 taxa genetically associated with both BMI and T2D, which formed an interactive network.

Our findings provide evidence for the GM-mediated links between obesity and T2D. The identification of relevant GM taxa offers valuable insights into the potential role of the microbiome in these diseases.