Gut microbial metabolites in cutaneous inflammation: shared mechanisms and therapeutic opportunities

Cutaneous inflammation is influenced by systemic signals beyond the skin, and gut microbial metabolites contribute to skin homeostasis and inflammatory responses. Major classes of gut-derived metabolites, including short-chain fatty acids, tryptophan-derived compounds, and secondary bile acids, may shape cutaneous inflammation through immune, neural, and endocrine pathways. However, current research remains fragmented across metabolite classes and pathways, and cross-pathway interactions remain unclear. As a result, the relationship between metabolite disturbances and distinct inflammatory phenotypes remains incompletely understood. Atopic dermatitis and chronic spontaneous urticaria are used as representative examples of this variability. This review summarizes major metabolite classes, the pathways linking them to cutaneous inflammation, and current therapeutic strategies targeting these pathways. Therapeutic strategies targeting gut microbial metabolites include direct metabolite supplementation, microbiome-targeted strategies that modify metabolite output, and indirect host-directed interventions. Available evidence suggests that gut microbial metabolites may serve as potential therapeutic targets in cutaneous inflammation. However, current limitations include context-dependent effects, limited causal evidence, variable treatment response, and unresolved issues in delivery and tissue specificity.