, Jie Zheng 2
, Junpeng Zhao 3
, Yuhong Yao 4
, Dongxue Gao 5
, Wenjie Qi 6
, Yanhong Liu 2
, Jinyin Yan 7
2Clinical Laboratory, Tangshan Fengnan District Hospital, Hebei, China
3Institute of Drug Inspection and Testing, Tangshan Food and Drug Comprehensive Inspection and Testing Center, Hebei, China
4Department of Reproductive Genetics, Tangshan Maternal and Children Health Hospital, Hebei, China
5Department of Nursing, Tangshan Gongren Hospital, Hebei, China
6Obstetrics and Gynecology Department, Tangshan Maternal and Children Health Hospital, Hebei, China
7Department of Breast Surgery, Tangshan Central Hospital, Hebei, China
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.