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Gut and skin microbiome-metabolome pathways in vitiligo: from dysbiosis to immune activation and melanocyte dysfunction.

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Title: Gut and skin microbiome-metabolome pathways in vitiligo: from dysbiosis to immune activation and melanocyte dysfunction.
Authors: Ruiz-Pozo VA; Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador., Tamayo-Trujillo R; Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador., Cadena-Paredes AS; Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador., Guevara-Ramírez P; Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador., Cadena-Ullauri S; Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador., Paz-Cruz E; Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador., Zambrano AK; Centro de Investigación Genética y Genómica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador.
Source: Frontiers in immunology [Front Immunol] 2026 Sep 15; Vol. 17, pp. 1952635. Date of Electronic Publication: 2026 Sep 15 (Print Publication: 2026).
Publication Type: Journal Article; Review
Language: English
Journal Info: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Imprint Name(s): Original Publication: [Lausanne : Frontiers Research Foundation]
MeSH Terms: Vitiligo*/metabolism , Vitiligo*/immunology , Vitiligo*/microbiology , Dysbiosis*/immunology , Dysbiosis*/metabolism , Melanocytes*/immunology , Melanocytes*/metabolism , Skin Microbiome*/immunology , Gastrointestinal Microbiome*/immunology , Skin*/microbiology , Skin*/immunology , Skin*/metabolism , Metabolome*, Humans ; Animals
Abstract: Vitiligo is an autoimmune depigmenting disorder driven by genetic susceptibility, oxidative stress, immune dysregulation, and progressive melanocyte loss. Emerging microbiome-metabolome evidence suggests that gut and skin dysbiosis may contribute to disease progression through the gut-skin axis. This review integrates current evidence linking microbial imbalance with immune activation and melanocyte dysfunction in vitiligo. Studies in patients and experimental vitiligo models show altered gut and skin microbial diversity, enrichment of inflammation-associated taxa, depletion of commensal bacteria, impaired short-chain fatty acid biosynthesis, and disruption of tryptophan-indole, kynurenine, bile acid, taurine, riboflavin, and oxidative stress-related metabolic pathways. These alterations may weaken epithelial barrier integrity, impair immune tolerance, promote systemic low-grade inflammation, and increase melanocyte vulnerability to mitochondrial dysfunction, reactive oxygen species accumulation, impaired melanogenesis, apoptosis, and autoantigen exposure. Dysbiosis-associated metabolic remodeling may affect key immunometabolic pathways, including AhR-mediated tryptophan-kynurenine signaling, SCFA-dependent GPCR/HDAC regulation, IFN-γ-JAK/STAT-CXCL9/CXCL10 inflammatory amplification, and NF-κB/inflammasome-mediated innate immune priming. Together, these mechanisms may enhance dendritic cell activation, Th1/Th17 polarization, autoreactive CD8+ T-cell recruitment, and persistence of melanocyte-specific resident memory T cells. Current evidence supports a biologically plausible link between microbiome-metabolome disruption and autoimmune melanocyte loss in vitiligo. However, causality remains unproven. Longitudinal, multi-omics, and functional studies are required to define whether microbial and metabolic signatures act as biomarkers, mechanistic drivers, or therapeutic targets in vitiligo.
(Copyright © 2026 Ruiz-Pozo, Tamayo-Trujillo, Cadena-Paredes, Guevara-Ramírez, Cadena-Ullauri, Paz-Cruz and Zambrano.)
Competing Interests: The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Contributed Indexing: Keywords: autoimmune inflammation; dysbiosis; gut–skin axis; melanocyte dysfunction; metabolome; microbiome; vitiligo
Entry Date(s): Date Created: 20260930 Date Completed: 20260930 Latest Revision: 20261001
Update Code: 20261001
PubMed Central ID: PMC13620461
DOI: 10.3389/fimmu.2026.1952635
PMID: 42812837
Database: MEDLINE
Description
ISSN:1664-3224
DOI:10.3389/fimmu.2026.1952635