Circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis: a two-step bidirectional Mendelian randomization study

Changhong Miao; Lu Xiao; Xinyi Xu; Shuoxuan Huang; Jiajin Liu; Kuang Chen

doi:10.3389/fnut.2023.1268893

Circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis: a two-step bidirectional Mendelian randomization study

Front Nutr. 2023 Sep 26:10:1268893. doi: 10.3389/fnut.2023.1268893. eCollection 2023.

Authors

Changhong Miao^{1

2}, Lu Xiao^{1

2}, Xinyi Xu^{1

2}, Shuoxuan Huang^{1

2}, Jiajin Liu^{1

2}, Kuang Chen^{1

2}

Affiliations

¹ First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
² National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.

Abstract

Background: The relationship between gut microbiota and the occurrence of cholecystitis remains unclear. Existing research lacks a clear understanding of how circulating vitamin levels modulate this relationship. Therefore, our study aims to investigate whether circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis using a two-step bidirectional Mendelian randomization approach.

Methods: In this study, we initially employed Linkage Disequilibrium Score Regression (LDSC) analysis to assess the genetic correlation of five circulating vitamin level genome-wide association study (GWAS) summary datasets, thereby avoiding potential sample overlap. Subsequently, we conducted a two-step analysis to investigate the causal effects between gut microbiota and cholecystitis. In the second step, we explored the causal relationship between circulating vitamin levels and cholecystitis and identified the mediating role of vitamin D. The primary method used for causal analysis was the inverse variance-weighted approach. We performed additional sensitivity analyses to ensure result robustness, including the cML-MA method and reverse Mendelian randomization (MR) analysis.

Results: An increment of one standard deviation in RuminococcaceaeUCG003 was associated with a 25% increased risk of cholecystitis (OR = 1.25, 95%CI = 1.01-1.54, p = 0.04), along with a 3% decrease in 25-hydroxyvitamin D levels (OR = 0.97, 95%CI = 0.944-0.998, p = 0.04). However, following the rigorous Bonferroni correction, every one standard deviation decrease in circulating vitamin D levels was associated with a 33% increased risk of cholecystitis (OR = 0.67, 95%CI = 0.49-0.90, p = 0.008, P_adjust = 0.04). Thus, the potential link between gut microbiota and cholecystitis risk might be mediated by circulating vitamin D levels (proportion mediated = 5.5%). Sensitivity analyses provided no evidence of pleiotropy.

Conclusion: Our study results suggest that an elevated abundance of specific gut microbiota is associated with an increased susceptibility to cholecystitis, with the causal relationship being mediated by circulating vitamin D levels. Further large-scale randomized controlled trials are necessary to validate the causal effects of gut microbiota on cholecystitis risk. This study provides novel insights into cholecystitis prevention through the regulation of gut microbiota.

Keywords: Mendelian randomization; causal relationship; cholecystitis; circulating vitamin levels; gut microbiota.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Scientific Research Project of the Tianjin Education Commission (project number: 2021KJ144).