ArticlemSystems2026
Integrative multi-omics analysis reveals gut-skin axis mechanisms and novel therapeutic target
Article in mSystems, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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9 authors.
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Abstract
The gut-skin axis represents a critical but poorly understood pathway in atopic dermatitis (AD) pathogenesis. This study aimed to establish causal relationships between gut microbiota and AD risk while identifying key molecular bridges and therapeutic targets. We integrated multiple analytical approaches, including single-cell RNA sequencing analysis of skin biopsies from five AD patients and four healthy controls, intercellular communication network analysis, pseudotime trajectory inference, reverse drug prediction, molecular docking, and molecular dynamics simulations. Analysis revealed increased keratinocyte heterogeneity and enhanced immune cell communication in atopic dermatitis (AD) samples. Intersection analysis between gut microbial metabolite-associated genes and skin pathology-related genes identified seven key bridging genes ( IMPORTANCE: Genetic-level evidence of gut microbiota causality in atopic dermatitis: this study established a causal relationship between specific gut microbiota and the risk of atopic dermatitis at the genetic level, providing strong genetic evidence for the "gut-skin axis" theory. GALE is identified as a novel therapeutic target with redefined methotrexate mechanism: molecular docking study unexpectedly found that GALE binding affinity of MTX was significantly higher than that of its classical target TYMS, suggesting that GALE may be an important but previously unrecognized target of MTX in the treatment of AD. Multi-omics integration framework reveals increased keratinocyte heterogeneity: integrating single-cell RNA sequencing and computational pharmacology provided a cellular and molecular basis for understanding the characteristics of chronicity and recurrence of the disease.
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