A study on the causal relationship between the gut microbiome and herpes zoster using Mendelian randomization
Authors: Meng Zenan , Wang Tingting , Liao Yue , Li Xinzhi 
Published: August 2024

IntroductionThe relationship between herpes zoster recurrence and the gut microbiome was not studied. We analyzed data on the gut microbiome and herpes zoster from the Large-Scale Genome-Wide Association Study (GWAS) database using bidirectional Mendelian randomization. For the first time, we identified a potentially bidirectional causal relationship between the gut microbiome and herpes zoster (HZ). These findings are groundbreaking and hold promise for new directions in the treatment of HZ, a global disease.Background and aimsHZ had a high global incidence, characterized by shingled blisters, blood blisters, and neuropathic pain, and could develop in various parts of the body, including the ear and throat. It was believed its onset was closely related to old age and infirmity. Some studies reported that the incidence of herpes zoster in patients with inflammatory intestinal diseases (such as Crohn’s disease and ulcerative colitis) was higher than in the general population. Existing studies attributed this to the reactivation of varicella-zoster virus (VZV) due to autoinflammatory attacks and immunosuppressive drugs. This provided a basis for exploring the new pathogenesis of HZ and investigating whether there was a relationship between intestinal auto-flora and the development of HZ. This study aimed to examine this potential relationship using bidirectional Mendelian analyses.MethodsGWAS data on HZ and gut microbiota were obtained from FinnGen, the Mibiogen consortium, and HZ meta-analysis data from the IEU Open GWAS Project. These data were subjected to two-sample Mendelian randomization (MR) analysis to determine if there is a causal relationship between gut microbiota and HZ. Additionally, bidirectional Mendelian analyses were conducted to identify the direction of causality and to clarify any potential interactions.ResultsIn our Mendelian Randomization (MR) analysis, we identified, for the first time, two gut microbes that might be associated with HZ reactivation. In the reverse MR analysis, four gut microbiota showed a potential association between the genetic susceptibility of gut microbiota and HZ reactivation. We found that genus Tyzzerella3 (OR: 1.42, 95% CI: 1.17–1.72, FDR &lt; 0.1) may be strongly correlated with an increased probability of HZ (ICD-10: B02.901) reactivation. Additionally, phylum Cyanobacteria was identified as a potential risk factor for the onset of HZ rekindling (OR: 1.42, 95% CI: 1.09–1.87). Analyzing the results of the reverse MR, we also identified a potential inhibitory effect (OR: 0.91, 95% CI: 0.84–0.99) of HZ onset on the genus Eubacteriumhallii group in the gut, suggesting that HZ might reduce its abundance. However, genus Escherichia/Shigella (OR: 1.11, 95% CI: 1.01–1.22), genus Veillonella (OR: 1.16, 95% CI: 1.04–1.30), and phylum Proteobacteria (OR: 1.09, 95% CI: 1.01–1.18) appeared to act as potential protective factors, indicating that the relative abundance and viability of these three bacteria increased in the HZ state.ConclusionWe identified the influence of gut flora as a new causative factor for HZ reactivation. Additionally, we found that individuals suffering from HZ might potentially impact their gut flora. Specific bacterial taxa that could influence the onset and progression of HZ were identified, potentially providing new directions for HZ treatment.