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Front Immunol. 2024 Feb 2;15:1297240. doi: 10.3389/fimmu.2024.1297240. eCollection 2024.


BACKGROUND: 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.

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

PMID:38370414 | PMC:PMC10869565 | DOI:10.3389/fimmu.2024.1297240

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What is a bi-directional two-sample Mendelian randomization (2SMR) analysis? Answer: 

Mendelian randomisation is a statistical approach that uses genetics to provide information about the relationship between an exposure and outcome (a type of instrumental variable analysis) [1]


Additionally, bi-directional Mendelian randomisation can be used to assess in which direction causality is most likely to flow (1).
In bi-directional Mendelian randomisation, Mendelian randomisation analyses are performed in both directions (exposure to outcome, and outcome to exposure). [1]

The summary concludes that there is 'evidence for the causality between GM [gut microbiota] and inflammatory skin diseases.' [1]

End Notes

[1] Making sense of Mendelian randomisation and its use in health research
A short overview
Sean Harrison, Laura Howe and Alisha R. Davies




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