Association between Depression, Anxiety Symptoms, Bacteroides Stercoris Abundance in Stool and Functional Constipation: A Bidirectional Two-Sample Mendelian Randomization Analysis

Abstract

Background Globally, functional constipation (FC) is a significant health problem. Therefore, greater understanding of the modifiable risk factors is needed to develop effective treatment and preventive strategies. The presence of depression symptoms (DS), anxiety symptoms (AS), and Bacteroides stercoris abundance in stool (BSAIS) has been found to be correlated with FC based on the previous observational study. Nevertheless, the causal relationship between these factors and FC remains uncertain due to observational study limitations. Methods Mendelian randomization (MR) leverages genetic variants as instrumental variables (IVs), exploiting genetically determined variability to evaluate causal relationships. In this two-sample MR analysis, genetic data were obtained from separate cohorts with DS AS, BSAIS, and FC. Genome-wide association studies (GWAS) identified genetic variants associated with DS, AS, BSAIS, and FC, which were utilized as IVs to infer causality.The study utilized bidirectional MR analysis to examine the influence of DS AS, and BSAIS on the risk of FC, as well as the potential for reverse causation. Subsequently, sensitivity tests including MR Egger, Inverse variance weighted (IVW), and MR-egger_intercept were performed to evaluate heterogeneity and pleiotropy in the IVs, thereby providing a reliable and confident estimation of the causal effect. Results Utilizing bidirectional two-sample MR analysis, we investigated the potential causal associations between DS, AS, BSAIS, and FC using data from the IEU open GWAS database. Our analysis, based on the IVW method of two-sample MR analysis, revealed significant causal effects of DS (odds ratio [OR] = 1.122, 95% confidence interval [CI]: 1.031-1.221, P = 0.008), AS (OR = 1.129, 95% CI: 1.037-1.230, P = 0.005), and BSAIS (OR = 1.137, 95% CI: 1.048-1.233, P = 0.002) on FC. Furthermore, we observed reverse causal effects of FC on DS (OR = 1.156, 95% CI: 1.048-1.275, P = 0.004) and AS (OR = 1.164, 95% CI: 1.057-1.281, P = 0.002). Sensitivity analyses did not reveal any evidence of heterogeneity or pleiotropy in the IVs, as indicated by P values exceeding 0.05. Conclusion This study suggests a potential causal relationship between DS, AS, BSAIS, and FC, along with the presence of reverse causality. No heterogeneity or pleiotropy were revealed by sensitivity tests, making these findings reliable and confident. The mitigation of symptoms of depression and anxiety and manipulation of gastrointestinal microbiota composition may potentially ameliorate symptoms of FC, and vice versa.