ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
This article is part of the Research TopicMetabolism and Tumor Microenvironment Nexus in Neuro-OncologyView all articles
Causality of Circulating Vitamins on Infectious Diseases: Integrating Mendelian Randomization and In Vivo Evidence
Provisionally accepted
- 1Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
- 2China-Japan Friendship Hospital, Beijing, China
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Background: Clinical studies have established an association between infections and circulating vitamin levels. However, the relationship stratified by specific pathogen types remains underexplored. More importantly, the causal direction of this association is still unclear. Methods: We utilized summary-level data from genome-wide association studies (GWAS) of European ancestry, sourced from the UK Biobank (UKB) and FinnGen consortium. A two-sample, bidirectional Mendelian randomization (MR) analysis was employed to investigate the genetic causal relationships between infectious diseases (categorized as bacterial or viral) and circulating levels of vitamins A, B6, B12, C, D, 25-hydroxyvitamin D (25(OH)D), and E. The inverse variance weighted (IVW) method served as the primary analytical approach. Sensitivity analyses were conducted to 2 validate the robustness of the findings. Furthermore, we employed the cecal ligation and puncture (CLP) model in mice to assess the impact of sepsis on serum 25(OH)D levels. Results: Genetically predicted higher circulating vitamin E levels were associated with an increased risk of viral infection (OR = 1.45, 95% CI: 1.10–1.88). Conversely, genetic predisposition to bacterial infection was associated with lower circulating 25(OH)D levels (OR = 0.96, 95% CI: 0.93–0.99). In vivo experiments confirmed a significant decrease in serum 25(OH)D levels in CLP group mice compared to the Sham group (Sham: 90.7 ± 1.7 vs. CLP: 47.9 ± 5.6). No causal relationships were identified between infections and other vitamins. Conclusion: This study provides evidence for a potential causal link between elevated vitamin E levels and increased susceptibility to viral infection, as well as between bacterial infection and reduced 25(OH)D levels. Furthermore, our in vivo data demonstrated that sepsis (induced by intraperitoneal bacterial infection) led to a significant decrease in serum 25(OH)D levels.
Keywords: Infection, vitamin, Bacteria, virus, Sepsis
Received: 29 Jul 2025; Accepted: 04 Nov 2025.
Copyright: © 2025 Tang, Gong, Shi, Zhang, Sun and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lichao Sun, xccxyy@126.com
Wei Chen, cwdoctor@shutcm.edu.cn
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