Related Experiment Video
Updated: Jun 22, 2025
Rapid Isolation of Dorsal Root Ganglion Macrophages
Published on: September 7, 2019
Genetically predicted immune cells mediate the association between gut microbiota and neuropathy pain
Zhixuan Lan1, Yi Wei1, Kan Yue1
1Department of Pain Medicine, The Second Affiliated Hospital of Guangxi Medical University, Guangxi, Nanning, 530005, China.
Background:
Previous observational studies have indicated a complex association between gut microbiota (GM) and neuropathic pain (NP). Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian randomization (MR) approach to investigate the causal relationship between GM and neuropathic pain including post-herpetic neuralgia (PHN), painful diabetic peripheral neuropathy (PDPN), and trigeminal neuralgia (TN), as well as to explore the potential mediation effects of immune cells.
Methods:
We performed a two-step, two-sample Mendelian randomization study with an inverse variance-weighted (IVW) approach to investigate the causal role of GM on three major kinds of NP and the mediation effect of immune cells between the association of GM and NP. In addition, we determine the strongest causal associations using Bayesian weighted Mendelian randomization (BWMR) analysis. Furthermore, we will investigate the mediating role of immune cells through a two-step Mendelian randomization design.
Results:
We identified 53 taxonomies and pathways of gut microbiota that had significant causal associations with NP. In addition, we also discovered 120 immune cells that exhibited significant causal associations with NP. According to the BWMR and two-step Mendelian randomization analysis, we identified the following results CD4 on CM CD4 + (maturation stages of T cell) mediated 6.7% of the risk reduction for PHN through the pathway of fucose degradation (FUCCAT.PWY). CD28 + DN (CD4-CD8-) AC (Treg) mediated 12.5% of the risk reduction for PHN through the influence on Roseburia inulinivorans. CD45 on lymphocyte (Myeloid cell) mediated 11.9% of the risk increase for TN through the superpathway of acetyl-CoA biosynthesis (PWY.5173). HLA DR + CD8br %T cell (TBNK) mediated 3.2% of the risk reduction for TN through the superpathway of GDP-mannose-derived O-antigen building blocks biosynthesis (PWY.7323). IgD-CD38-AC (B cell) mediated 7.5% of the risk reduction for DPN through the pathway of thiazole biosynthesis I in E. coli (PWY.6892).
Discussion:
These findings provided evidence supporting the causal effect of GM with NP, with immune cells playing a mediating role. These findings may inform prevention strategies and interventions directed toward NP. Future studies should explore other plausible biological mechanisms.
Insights
Gut microbiota causally influences neuropathic pain (NP), with specific immune cells mediating this effect. These findings may guide novel prevention and treatment strategies for NP.
Area of Science:
- Genetics
- Immunology
- Microbiology
Background:
- Observational studies suggest a link between gut microbiota (GM) and neuropathic pain (NP), but underlying mechanisms are unclear.
- Investigating the causal relationship and immune cell mediation is crucial for understanding NP pathogenesis.
Purpose of the Study:
- To investigate the causal relationship between GM and NP (including PHN, PDPN, TN) using Mendelian randomization (MR).
- To explore the potential mediation effects of immune cells in the GM-NP association.
Main Methods:
- A two-step, two-sample Mendelian randomization (MR) study utilizing inverse variance-weighted (IVW) and Bayesian weighted Mendelian randomization (BWMR) approaches.
- Investigated causal associations between 53 GM taxonomies/pathways and 120 immune cells with NP.
- Examined immune cell mediation using a two-step MR design.
Main Results:
- Significant causal associations were found between specific gut microbiota and NP.
- Significant causal associations were identified between 120 immune cells and NP.
- Specific immune cells (e.g., CD4+ T cells, Tregs, Myeloid cells, TBNK, B cells) were found to mediate the relationship between GM and NP, influencing risk for PHN, TN, and DPN through various metabolic pathways.
Conclusions:
- This study provides evidence for a causal effect of GM on NP, with immune cells acting as key mediators.
- Findings suggest potential therapeutic targets within the gut microbiota and immune system for NP management.
- Further research is warranted to elucidate other biological mechanisms involved in the GM-NP axis.
