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

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. 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. 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. 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.

Gu Y ，Zhang W ，Zhao W ，Zeng X ... -  《-》

The causal relationship between gut microbiota and inflammatory dermatoses: a Mendelian randomization study.

Mao R ，Yu Q ，Li J 《Frontiers in Immunology》

Association between gut microbiota and pan-dermatological diseases: a bidirectional Mendelian randomization research.

Gut microbiota has been associated with dermatological problems in earlier observational studies. However, it is unclear whether gut microbiota has a causal function in dermatological diseases. Thirteen dermatological diseases were the subject of bidirectional Mendelian randomization (MR) research aimed at identifying potential causal links between gut microbiota and these diseases. Summary statistics for the Genome-Wide Association Study (GWAS) of gut microbiota and dermatological diseases were obtained from public datasets. With the goal of evaluating the causal estimates, five acknowledged MR approaches were utilized along with multiple testing corrections, with inverse variance weighted (IVW) regression serving as the main methodology. Regarding the taxa that were causally linked with dermatological diseases in the forward MR analysis, reverse MR was performed. A series of sensitivity analyses were conducted to test the robustness of the causal estimates. The combined results of the five MR methods and sensitivity analysis showed 94 suggestive and five significant causal relationships. In particular, the genus Eubacterium_fissicatena_group increased the risk of developing psoriasis vulgaris (odds ratio [OR] = 1.32, pFDR = 4.36 × 10-3), family Bacteroidaceae (OR = 2.25, pFDR = 4.39 × 10-3), genus Allisonella (OR = 1.42, pFDR = 1.29 × 10-2), and genus Bacteroides (OR = 2.25, pFDR = 1.29 × 10-2) increased the risk of developing acne; and the genus Intestinibacter increased the risk of urticaria (OR = 1.30, pFDR = 9.13 × 10-3). A reverse MR study revealed insufficient evidence for a significant causal relationship. In addition, there was no discernible horizontal pleiotropy or heterogeneity. This study provides novel insights into the causality of gut microbiota in dermatological diseases and therapeutic or preventive paradigms for cutaneous conditions.

Wang Y ，Yao T ，Lin Y ，Ge H ，Huang B ，Gao Y ，Wu J ... -  《Frontiers in Cellular and Infection Microbiology》

The causal relationship between gut microbiota and immune skin diseases: A bidirectional Mendelian randomization.

Increasing evidence suggests that alterations in gut microbiota are associated with a variety of skin diseases. However, whether this association reflects a causal relationship remains unknown. We aimed to reveal the causal relationship between gut microbiota and skin diseases, including psoriasis, atopic dermatitis, acne, and lichen planus. We obtained full genetic association summary data for gut microbiota, psoriasis, atopic dermatitis, acne, and lichen planus from public databases and used three methods, mainly inverse variance weighting, to analyze the causal relationships between gut microbiota and these skin diseases using bidirectional Mendelian randomization, as well as sensitivity and stability analysis of the results using multiple methods. The results showed that there were five associated genera in the psoriasis group, seven associated genera were obtained in the atopic dermatitis group, a total of ten associated genera in the acne group, and four associated genera in the lichen planus group. The results corrected for false discovery rate showed that Eubacteriumfissicatenagroup (P = 2.20E-04, OR = 1.24, 95%CI:1.11-1.40) and psoriasis still showed a causal relationship. In contrast, in the reverse Mendelian randomization results, there was no evidence of an association between these skin diseases and gut microbiota. We demonstrated a causal relationship between gut microbiota and immune skin diseases and provide a new therapeutic perspective for the study of immune diseases: targeted modulation of dysregulation of specific bacterial taxa to prevent and treat psoriasis, atopic dermatitis, acne, and lichen planus.

Feng F ，Li R ，Tian R ，Wu X ，Zhang N ，Nie Z ... -  《PLoS One》

Gut microbiota and acne: A Mendelian randomization study.

Cao Q ，Guo J ，Chang S ，Huang Z ，Luo Q ... -  《-》