The causality between gut microbiome and chronic regional pain: a Mendelian randomization analysis

Qing-Ao Xiao; Lei Qin; Jing Yu; Yin-Tao Hu; Lin-Feng Ai; De-Cheng Wang; Xuan Xia; Xiao-Lin Zhang

doi:10.3389/fmicb.2024.1329521

The causality between gut microbiome and chronic regional pain: a Mendelian randomization analysis

Front Microbiol. 2024 Feb 29:15:1329521. doi: 10.3389/fmicb.2024.1329521. eCollection 2024.

Authors

Qing-Ao Xiao^#^{1

2}, Lei Qin^#^{1

2}, Jing Yu^#^{1

2}, Yin-Tao Hu^#^{1

2}, Lin-Feng Ai^#^{1

2}, De-Cheng Wang^#^{3

4

5}, Xuan Xia^#^{3

4

5}, Xiao-Lin Zhang^#^{1

2}

Affiliations

¹ Department of Interventional Radiology, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, China.
² Department of Interventional Radiology, Yichang Central People's Hospital, Yichang, Hubei, China.
³ Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, China.
⁴ Institute of Infection and Inflammation, China Three Gorges University, Yichang, Hubei, China.
⁵ Department of Physiology and Pathophysiology, College of Basic Medical Science, China Three Gorges University, Yichang, Hubei, China.

^# Contributed equally.

Abstract

Background: Numerous investigations have underscored the causal effect between chronic pain (CP) and gut microbiota, jointly contributing to the onset and development of widespread CP. Nonetheless, there was still uncertainty about the causal effect between gut microbiota and chronic regional pain (CRP).

Methods: Genome-wide association study (GWAS) summary data of gut microbial taxa (MiBioGen Consortium: 211 microbiotas and the Dutch Microbiome Project: 207 microbiotas) and eight types of CRP were used to reveal the causal effect between persistent pain in a specific region of the body and gut microbiota. A two-sample bidirectional Mendelian randomization (MR) design was used. In order to ensure the accuracy of the results, multiple sensitivity analyses were employed.

Results: This study uncovered significant causal associations between six gut microbial taxa and three types of CRP (forward: Genus Parabacteroides for general pain; Class Bacteroidia, Order Bacteroidales, and Phylum Bacteroidetes for back pain. Reverse: knee pain for Genus Howardella and Order Coriobacteriales) by forward and reverse MR analysis. These findings had been verified by a rigorous Bonferroni correction. Furthermore, this research identified 19 microbial taxa that exhibited potential correlations with four types of CRP. There are no significant or potential gut microbiotas that were associated with other types of CRP, including fascial pain, stomach or abdominal pain, and hip pain.

Conclusion: This two-sample bidirectional MR analysis unveiled the causality between gut microbial taxa and eight CRP conditions. The findings reveal the interplay between CRP and 6 gut microbiotas while also delineating 19 potential specific microbial taxa corresponding to diverse locations of persistent pain.

Keywords: Mendelian randomization; causality; chronic regional pain; genome-wide association study; gut microbiome.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the National Natural Science Foundation of China (no. 31772709) and the Hubei Natural Science Foundation (2015CFB316) of China.