From Gut to Heart: Mendelian Randomization Study Reveals the Causal Relationship Between Gut Microbiota and N-Terminal Pro-B-Type Natriuretic Peptide.

Abstract

Background: This study aimed to clarify the potential causal relationship between gut microbiota (GM) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) using Mendelian randomization (MR) analysis.

Methods: Genome-wide association study of intestinal flora and NT-proBNP was conducted, and the instrumental variables (IVs) were screened out to assess the causal association between intestinal flora and NT-proBNP. The 2-sample MR analysis was performed using the inverse variance weighted (IVW), MR-Egger, weighted model and simple model methods, respectively, to assess the causal association between intestinal flora and NT-proBNP using the odds ratio. Sensitivity analyses were also performed using the leave-one-out method and MR-Egger intercept test. The MR-PRESSO global test was used to detect horizontal pleiotropy, and Cochran Q was used to detect heterogeneity. Finally, forest plots, scatter plots, and funnel plots of the IVs were generated.

Results: Based on the IVW method, a total of 9 out of 104 GM genera were identified as causally associated with NT-proBNP levels (P < .05). The genera Holdemanella (β = -0.19, 95% CI: -0.36 to -0.01, P = .037), Coprococcus 2 (β = -0.27, 95% CI: -0.54 to 0.00, P = .047), Ruminococcaceae UCG 004 (β = -0.23, 95% CI: -0.45 to -0.02, P = .032), and Alistipes (β = -0.29, 95% CI: -0.55 to -0.03, P = .031) were negatively associated with NT-proBNP; genera Actinomyces (β = 0.22, 95% CI: 0.01-0.44, P = .042), Lachnospiraceae UCG 008 (β = 0.27, 95% CI: 0.1-0.44, P = .002), Eubacterium fissicatena group (β = 0.17, 95%CI: 0.01-0.32, P = .033), Eubacterium rectale group (β = 0.40, 95% CI: 0.13-0.67, P = .003), and Eubacterium ventriosum group (β = 0.26, 95% CI: 0.02-0.49, P = .032) were positively associated with NT-proBNP. In addition, the results of the sensitivity analysis of the leave-one-out method were stable, there was no horizontal multiplicity in the MR-Egger intercept test and the MR-PRESSO global test, and there was no heterogeneity in the Cochran Q-test.

Conclusions: The study found the causal relationship between GM and NT-proBNP. As a clinical predictor of heart failure, NT-proBNP levels could potentially be modulated through clinical interventions involving GM, further reducing the risk of heart failure.