AUTHOR=Deng Zhimin , Liu Yali , Wang Haiying , Luo Tianyuan 

TITLE=Genetic insights into the gut microbiota, herpes zoster, and postherpetic neuralgia: a bidirectional two-sample Mendelian randomization study

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1366824

DOI=10.3389/fgene.2024.1366824

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>An increasing amount of evidence suggests that gastrointestinal diseases are risk factors for herpes zoster (HZ) and postherpetic neuralgia (PHN). Among them, the gut microbiota may play a crucial role in this process. Therefore, this study aims to explore the potential causal association between the gut microbiota and HZ and PHN.</p></sec><sec><title>Methods</title><p>Bidirectional two-sample Mendelian randomization (MR) analysis was used to detect the causal effect between HZ and PHN and the gut microbiota. Gut microbiota data were derived from the MiBioGen consortium, while HZ and PHN data were obtained from the FinnGen database. We selected single-nucleotide polymorphisms (SNPs) as instrumental variables with a threshold of <italic>p</italic> &lt; 1 × 10⁻⁵ for the association with the gut microbiota in forward MR analysis and <italic>p</italic> &lt; 5 × 10<sup>⁻8</sup> for the association with HZ or PHN in reverse MR analysis and then removed SNPs in linkage disequilibrium (<italic>r</italic><sup>2</sup> &lt; 0.001) within a distance of 10,000 kb for both the gut microbiota and HZ and PHN. These SNPs were utilized to assess the causal effect between exposures and outcomes using inverse-variance weighting (IVW), MR–Egger, weighted mean, and weighted median tests.</p></sec><sec><title>Results</title><p>The class Deltaproteobacteria, order Desulfovibrionales, family Desulfovibrionaceae, and genus <italic>Coprococcus 2</italic> were found to reduce the risk of HZ, while the phylum Cyanobacteria, genus <italic>Eubacterium rectale</italic> group appeared to increase it. The class Coriobacteriia, order Coriobacteriales, family Coriobacteriaceae, genus <italic>Lachnospiraceae NK4A136</italic> and genus <italic>Ruminococcaceae UCG011</italic> were found to reduce the risk of PHN, while the genus <italic>Candidatus Soleaferrea</italic>, genus <italic>Eubacterium rectale</italic> group, and genus <italic>Methanobrevibacter</italic> appeared to increase it. Moreover, the onset of HZ was found to increase the level of the genus <italic>Eubacterium rectale</italic> group. These findings remained robust and unaffected by heterogeneity or horizontal pleiotropy among SNPs in both forward and reverse MR analysis.</p></sec><sec><title>Conclusion</title><p>This MR study provided evidence supporting a potential causal relationship between the gut microbiota and HZ and PHN. Moreover, we found that the causal effect between the gut microbiota and HZ is bidirectional. Further studies are required to clarify the biological mechanisms linking the gut microbiota and these conditions.</p></sec>