The associations between gut microbiota and inflammatory skin diseases: a bi-directional two-sample Mendelian randomization study.

Accumulating evidence shows that dysregulation of intestinal flora is associated with inflammatory skin diseases, specifically atopic dermatitis (AD), psoriasis (PSO), and rosacea (ROS). However, the causality is still unclear. To study the underlying causality between gut microbiota (GM) and AD, PSO, and ROS, a bi-directional two-sample Mendelian randomization (2SMR) analysis was conducted. Summary statistics of gut microbiota, AD, PSO, and ROS were extracted from large-scale genome-wide association studies (GWASs). In 2SMR analysis, in addition to the inverse variance weighted as the principal method for evaluating causal association, four different methods were also used. Sensitivity analysis and reverse 2SMR study were implemented to evaluate the robustness of 2SMR results or reverse causal relationship, respectively. A total of 24 specific gut microbiota species related to AD, PSO, and ROS were identified by 2SMR analysis. After using the Bonferroni method for multiple testing correction, family FamilyXIII (ID: 1957) [OR = 1.28 (1.13, 1.45), p = 9.26e-05] and genus Eubacteriumfissicatenagroup (ID: 14373) [OR = 1.20 (1.09, 1.33), p = 1.65e-04] were associated with an increased risk for AD and PSO, respectively. The genus Dialister showed a negative association, suggesting a protective role against both atopic dermatitis and rosacea. Our reverse 2SMR analysis indicated no reverse causality between these inflammatory skin diseases and the identified gut microbiota. In summary, this study provided evidence for the causality between GM and inflammatory skin diseases. These findings suggested that supplementing specific bacterial taxa may be an effective therapy for AD, PSO, and ROS.

Zhong Y ，Wang F ，Meng X ，Zhou L ... -  《Frontiers in Immunology》

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

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

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》

Skin microbiome and causal relationships in three dermatological diseases: Evidence from Mendelian randomization and Bayesian weighting.

Atopic dermatitis (AD), psoriasis (PSO), rosacea, and other related immune skin diseases are affected by multiple complex factors such as genetic and microbial components. This research investigates the causal relationships between specific skin microbiota and these diseases by using Mendelian randomization (MR), and Bayesian weighted Mendelian randomization (BWMR). We utilized genome-wide association study (GWAS) data to analyze the associations between various skin bacteria and three dermatological diseases. Single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) in MR methods, including inverse variance weighted (IVW), and MR Egger. BWMR was employed to validate results and address pleiotropy. The IVW analysis identified significant associations between specific skin microbiota and dermatological diseases. ASV006_Dry, ASV076_Dry, and Haemophilus_Dry were significantly positively associated with AD, whereas Kocuria_Dry was negatively associated. In PSO, ASV005_Dry was negatively associated, whereas ASV004_Dry, Rothia_Dry, and Streptococcus_Moist showed positive associations. For rosacea, ASV023_Dry was significantly positively associated, while ASV016_Moist, Finegoldia_Dry, and Rhodobacteraceae_Moist were significantly negatively associated. These results were corroborated by BWMR analysis. Bacterial species such as Finegoldia, Rothia, and Streptococcus play crucial roles in the pathogenesis of AD, PSO, and rosacea. Understanding these microbial interactions can aid in developing targeted treatments and preventive strategies, enhancing patient outcomes and quality of life.

Li X ，Chen S ，Chen S ，Cheng S ，Lan H ，Wu Y ，Qiu G ，Zhang L ... -  《-》

Association between allergic diseases and both psoriasis and psoriatic arthritis: a bidirectional 2-sample Mendelian randomization study.

Background An increasing body of observational studies has indicated a potential link between allergic diseases, namely atopic dermatitis (AD), allergic rhinitis (AR), allergic asthma (AA), and psoriasis (PSO) as well as psoriatic arthritis (PSA). However, the presence and causal direction of this association remain uncertain. Methods We conducted two-sample Mendelian randomization (TSMR) analyses utilizing summary statistics derived from genome-wide association studies (GWAS) consortia. The summary statistics were obtained from a substantial participant cohort, consisting of 116,000 individuals (21,000 AD cases and 95,000 controls), 462,933 individuals (26,107 AR cases and 436,826 controls), and 140,308 individuals (4859 AA cases and 135,449 controls). The summary statistics for PSO (9267 cases and 360,471 controls) and PSA (3186 cases and 240,862 controls) were sourced from the FinnGen database. The primary analytical approach employed inverse variance weighting (IVW) as the main method within TSMR. We validated our findings through a series of sensitivity analyses. Furthermore, we performed reverse TSMR analyses to evaluate the potential presence of reverse causality. Results Our investigation revealed a potential protective effect of AD against both PSO (OR = 0.922, 95% CI = 0.863-0.984, p = 0.015)and PSA(OR = 0.915, 95% CI = 0.843-0.993, p = 0.033). Moreover, employing inverse MR analysis, we obtained compelling evidence supporting the protective role of PSO in preventing AD (OR = 0.891, 95% CI = 0.829-0.958, p = 0.002), as well as AR (OR = 0.998, 95% CI = 0.996-0.999, p = 0.008), these associations remained statistically significant even after Bonferroni correction was applied to account for multiple comparisons. Furthermore, our findings did not reveal any substantial causal relationship between AA and either PSO or PSA. Conclusion Our study provides compelling evidence that PSO significantly confers protection against both AD and AR, while AD is likely to act as a protective factor for both PSO and PSA. Despite previous studies suggesting an association between allergic diseases and the incidence of PSO and PSA, our findings do not support this claim. To obtain more accurate and reliable conclusions regarding the causal mechanisms involved, larger sample sizes in randomized controlled trials or MR studies are warranted.

Zhao D ，Wu S ，Wang Y ，Zheng H ，Zhu M ... -  《-》