AUTHOR=Cai Yuxin , Wen Shuyang , Hu Jinjing , Wang Ziyi , Huang Guozhi , Zeng Qing , Zou Jihua 

TITLE=Multiple reports on the causal relationship between various chronic pain and gut microbiota: a two-sample Mendelian randomization study

JOURNAL=Frontiers in Neuroscience

VOLUME=18

YEAR=2024

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1369996

DOI=10.3389/fnins.2024.1369996

ISSN=1662-453X

ABSTRACT=<sec id="sec1"><title>Background</title><p>Previous evidence suggests a link between gut microbiota and chronic pain, but the causal relationship is not yet fully understood.</p></sec><sec id="sec2"><title>Methods</title><p>We categorized gut microbiota based on phylum, class, order, family, and genus levels and gathered pain-related information from the UKB and FinnGen GWAS project. Then, we conducted MR analysis to explore the potential causal relationship between gut microbiota and chronic pain at 12 specific locations.</p></sec><sec id="sec3"><title>Results</title><p>We have discovered a direct connection between genetic susceptibility in the gut microbiota (gut metabolites) and pain experienced at 12 specific locations. Notably, Serotonin (5-HT) and Glycine were found to be associated with a higher risk of pain in the extremities. On the other hand, certain microbial families and orders were found to have a protective effect against migraines. Specifically, the family Bifidobacteriaceae (IVW, FDR <italic>p</italic> = 0.013) was associated with a lower risk of migraines. Furthermore, the genus Oxalobacter (IVW, FDR <italic>p</italic> = 0.044) was found to be linked to an increased risk of low back pain. Importantly, these associations remained significant even after applying the Benjamini-Hochberg correction test. Our analysis did not find any heterogeneity in the data (<italic>p</italic> &gt; 0.05), as confirmed by the Cochrane’s <italic>Q</italic>-test. Additionally, both the MR-Egger and MR-PRESSO tests indicated no significant evidence of horizontal pleiotropy (<italic>p</italic> &gt; 0.05).</p></sec><sec id="sec4"><title>Conclusion</title><p>Our MR analysis demonstrated a causal relationship between the gut microbiota and pain, highlighting its potential significance in advancing our understanding of the underlying mechanisms and clinical implications of microbiota-mediated pain.</p></sec>