Investigating causal relationships between the gut microbiota and inflammatory skin diseases: A Mendelian randomization study

Abstract

Background: Numerous inflammatory skin diseases are associated with the gut microbiota. Studies of the association between gut microbiota and inflammatory skin diseases have yielded conflicting results owing to confounding factors, and the causal relationship between them remains undetermined. Methods: Two-sample Mendelian randomization (MR) was used to examine the association between gut microbiota and four common inflammatory skin diseases: acne, psoriasis, urticaria and atopic dermatitis. The summary statistics of the gut microbiota from the largest available genome-wide association study meta-analysis (n = 13,266) conducted by the MiBioGen consortium along with the summary statistics of the four diseases were obtained from the FinnGen consortium. Causal relationships were assessed using the inverse variance weighted (IVW), weighted median, MR-Egger and maximum likelihood methods, and several sensitivity analyses were performed to ensure the accuracy of the results. Finally, reverse and multivariable MR analyses were performed to verify the robustness of the results. Results: We found causal associations of Bacteroidaceae [odds ratio (OR), 2.25; 95% confidence interval (CI), 1.48–3.42; pivw = 0.0001], Allisonella (OR, 1.42; 95% CI, 1.18–1.70; pivw = 0.0002) and Bacteroides (OR, 2.25; 95% CI, 1.48–3.42; pivw = 0.0001) with acne, the Eubacterium fissicatena group with psoriasis (OR, 1.22; 95% CI, 1.10–1.35; pivw = 0.0002) and Intestinibacter with urticaria (OR, 1.28; 95% CI, 1.13–1.45; pivw = 0.0001). These results were corrected for a false discovery rate. Sensitivity analyses were performed to validate the robustness of the associations and reverse MR confirmed that the results were not influenced by the reverse effect. Conclusion: Our study revealed that some gut microbiota are risk factors for inflammatory skin diseases, providing new information on potential therapeutic targets. Additionally, a possible association with the gut–skin axis was confirmed. Further research is required to elucidate the mechanisms underlying these relationships.