# The causal effects between low back pain and cerebrospinal fluid metabolites: a two-sample Mendelian randomization study

## TL;DR

This study finds a causal link between specific cerebrospinal fluid metabolites and low back pain, suggesting potential targets for treatment.

## Contribution

The study identifies 12 CSF metabolites with causal effects on low back pain using Mendelian randomization.

## Key findings

- Five metabolites may inhibit low back pain risk, including Bilirubin and Butyrate.
- Seven metabolites increase low back pain risk, such as 2-hydroxyadipate and Indoleacetate.
- No significant heterogeneity or pleiotropy was detected in the analysis.

## Abstract

Observational studies have shown an association between cerebrospinal fluid (CSF) metabolites and low back pain (LBP), but the causal relationship between these factors remains unclear.

We performed a two-sample Mendelian randomization (MR) analysis to examine whether there is a causal relationship between CSF metabolites and LBP. We applied several MR methods, including inverse variance weighting, weighted median, MR-Egger, Wald ratio, and MR-PRESSO, to test the causal relationship and conducted a sensitivity analysis to assess the robustness of the results.

We identified a total of 12 CSF metabolites significantly associated with LBP, of which Bilirubin, 5,6-dihydrothymine, Erythronate, Mannitol/sorbitol, and Butyrate have a potential inhibitory causal effect on LBP risk (p < 0.05). Meanwhile, 2-hydroxyadipate, Gamma-glutamyl-alpha-lysine, Indoleacetate, N-acetylputrescine, Palmitoyl dihydrosphingomyelin, S-methylcysteine, and 2,3-dihydroxy-5-methylthio-4-pentenoate play a causal role in increasing the risk of LBP (p < 0.05). No significant estimates of heterogeneity or pleiotropy were detected.

Our study emphasizes the causal relationship between CSF metabolites and LBP risk, providing reference for clinical treatment and prognosis of LBP.

The online version contains supplementary material available at 10.1186/s41065-025-00374-y.