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From the Journals

Link Between Gut Microbiota and Skin Inflammation Uncovered

IL-15RA mediated 11% of the pathway between Veillonellaceae and eczema, supporting a role for inflammatory proteins in the gut-skin axis.

Conexiant

A recent Mendelian randomization study identified causal relationships between specific gut microbiota taxa, inflammatory cytokines, and inflammatory skin diseases, offering insights into potential mediating pathways along the gut-skin axis.

Published in Clinical, Cosmetic and Investigational Dermatology, the study utilized genome-wide association study data from the MiBioGen consortium (N=18,340) and the FinnGen biobank, as well as cytokine data from Olink’s Target Inflammation panel. The authors analyzed six inflammatory skin conditions: acne, allergic contact dermatitis, eczema, psoriasis vulgaris, psoriatic arthritis, and seborrheic dermatitis.

Using two-sample and multivariable Mendelian randomization (MR) methods, the researchers found that four gut microbiota taxa were causally associated with inflammatory skin diseases after false discovery rate (FDR) correction. The odds ratios (ORs) for these associations were as follows:

  • Eubacterium fissicatena (associated with psoriasis vulgaris): OR, 1.32; 95% CI, 1.16–1.50

  • Bacteroidaceae (acne): OR, 2.25; 95% CI, 1.48–3.42

  • Allisonella (acne): OR, 1.42; 95% CI, 1.18–1.70

  • Bacteroides (acne): OR, 2.25; 95% CI, 1.48–3.42

The inflammatory cytokine IL-18 receptor 1 (IL-18R1) was significantly associated with eczema (OR, 1.05; 95% CI, 1.03–1.08).

Mediation analysis identified IL-15 receptor subunit alpha (IL-15RA) and fibroblast growth factor 19 (FGF19) as intermediaries linking gut microbiota to inflammatory skin diseases. IL-15RA mediated 11% of the pathway between the bacterial family Veillonellaceae and eczema (OR for indirect effect, 0.992; 95% CI, 0.984–0.998). FGF19 mediated 6% of the pathway between LachnospiraceaeUCG001 and psoriatic arthritis (OR, 0.976; 95% CI, 0.944–0.998).

“These findings provide potential targets for therapeutic interventions in inflammatory skin diseases,” said Zirui Huang of the Department of Dermatology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.

The study also conducted a reverse MR analysis, identifying potential bidirectional relationships. A statistically significant association was found between psoriasis vulgaris and the genus Odoribacter (OR, 1.03; 95% CI, 1.00–1.06; P = .028), suggesting mutual influence. Additional reverse associations included an inverse link between acne and tumor necrosis factor beta, as well as between psoriasis vulgaris and IL-18R1.

Several microbial taxa were identified as potentially protective, although not all met FDR correction thresholds. These included Ruminococcaceae, LachnospiraceaeUCG001, Bifidobacterium, and Fusicatenibacter. Many of these microbes are known producers of short-chain fatty acids, which have been shown to influence systemic inflammation and immune responses.

To infer causality, the authors implemented multiple MR methodologies including inverse variance weighting, MR-Egger regression, and weighted median methods. Sensitivity analyses, such as the MR-PRESSO test and Cochran’s Q test, were performed to detect heterogeneity and horizontal pleiotropy. All significant findings withstood robustness checks.

This study is the first to use a two-step Mendelian randomization framework to examine whether inflammatory cytokines mediate the relationship between gut microbiota and skin inflammation. According to the authors, the findings provide genetic-level evidence supporting causal links between gut microbes, circulating inflammatory proteins, and inflammatory skin conditions.

The authors reported no conflicts of interest and stated that the study did not receive specific funding.