Causal associations of genetically predicted gut microbiota and blood metabolites with inflammatory states and risk of infections: a Mendelian randomization analysis

Yingjian Liu; Qian Zhu; Gongjie Guo; Zhipeng Xie; Senlin Li; Chengyang Lai; Yonglin Wu; Liansheng Wang; Shilong Zhong

doi:10.3389/fmicb.2024.1342653

Causal associations of genetically predicted gut microbiota and blood metabolites with inflammatory states and risk of infections: a Mendelian randomization analysis

Front Microbiol. 2024 Mar 22:15:1342653. doi: 10.3389/fmicb.2024.1342653. eCollection 2024.

Authors

Yingjian Liu^#¹, Qian Zhu^#², Gongjie Guo^{1

3}, Zhipeng Xie^{1

3}, Senlin Li^{1

3}, Chengyang Lai^{1

3}, Yonglin Wu³, Liansheng Wang⁴, Shilong Zhong^{1

3

4}

Affiliations

¹ Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
² Department of Neurosurgery, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou, Guangdong, China.
³ School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
⁴ Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

^# Contributed equally.

Abstract

Background: Inflammation serves as a key pathologic mediator in the progression of infections and various diseases, involving significant alterations in the gut microbiome and metabolism. This study aims to probe into the potential causal relationships between gut microbial taxa and human blood metabolites with various serum inflammatory markers (CRP, SAA1, IL-6, TNF-α, WBC, and GlycA) and the risks of seven common infections (gastrointestinal infections, dysentery, pneumonia, bacterial pneumonia, bronchopneumonia and lung abscess, pneumococcal pneumonia, and urinary tract infections).

Methods: Two-sample Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW), maximum likelihood, MR-Egger, weighted median, and MR-PRESSO.

Results: After adding other MR models and sensitivity analyses, genus Roseburia was simultaneously associated adversely with CRP (Beta _IVW = -0.040) and SAA1 (Beta _IVW = -0.280), and family Bifidobacteriaceae was negatively associated with both CRP (Beta _IVW = -0.034) and pneumonia risk (Beta _IVW = -0.391). After correction by FDR, only glutaroyl carnitine remained significantly associated with elevated CRP levels (Beta _IVW = 0.112). Additionally, threonine (Beta _IVW = 0.200) and 1-heptadecanoylglycerophosphocholine (Beta _IVW = -0.246) were found to be significantly associated with WBC levels. Three metabolites showed similar causal effects on different inflammatory markers or infectious phenotypes, stearidonate (18:4n3) was negatively related to SAA1 and urinary tract infections, and 5-oxoproline contributed to elevated IL-6 and SAA1 levels. In addition, 7-methylguanine showed a positive correlation with dysentery and bacterial pneumonia.

Conclusion: This study provides novel evidence confirming the causal effects of the gut microbiome and the plasma metabolite profile on inflammation and the risk of infection. These potential molecular alterations may aid in the development of new targets for the intervention and management of disorders associated with inflammation and infections.

Keywords: Mendelian randomization analysis; gut microbiome; infection; inflammation; metabolome.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the National Natural Science Foundation of China (grant number: 82274016 and 81872934) and the Science and Technology Program of Guangzhou (grant number: 2023B03J1251). The funders were not involved in designing the study; collecting, analyzing, or interpreting the data; or in writing or submitting the manuscript for publication.