Vitiligo, a depigmenting autoimmune skin disease characterized by melanocyte dysfunction or death, is known to be associated with an imbalance in gut microbiota. Oxidative stress plays a critical role in the pathogenesis of vitiligo. However, the complex promising interaction between abnormal accumulation of reactive oxygen species (ROS) in the skin and gut microbiota has remained unclear. Here, we compared transcriptome data of vitiligo lesions and normal skin and identified a high expression of oxidative stress-related genes in vitiligo lesions. We also established a vitiligo mouse model and found that the presence of gut microbiota influenced the expression of ROS-related genes. Depletion of gut microbiota reduced abnormal ROS accumulation and mitochondrial abnormalities in melanocytes, significantly improving depigmentation. Our findings from manipulating gut microbiota through cohousing, fecal microbiota transplantation (FMT), and probiotic supplementation showed that transferring gut microbiota from mice with severe vitiligo-like phenotypes exacerbated skin depigmentation while probiotics inhibited its progression. Targeted metabolomics of fecal, serum, and skin tissues revealed gut microbiota-dependent accumulation of hippuric acid, mediating excessive ROS in the skin. Elevated serum hippuric acid levels were also confirmed in vitiligo patients. Additionally, a microbiota-dependent increase in intestinal permeability in vitiligo mice mediated elevated hippuric acid levels, and we found that hippuric acid could directly bind to ROS-related proteins (NOS2 and MAPK14). Our results suggested the important role of gut microbiota in regulating vitiligo phenotypes and oxidative stress. We identified hippuric acid, a gut microbiota-host co-metabolite, as a critical mediator of oxidative stress in vitiligo skin and its binding targets (NOS2 and MAPK14), resulting in oxidative stress. Validation in a small human cohort suggested that hippuric acid could serve as a novel diagnostic biomarker and therapeutic target for vitiligo. These findings provided new insights into how gut microbiota regulates skin oxidative stress in vitiligo and suggested potential treatment strategies for the disease.

Purpose: Skin and subcutaneous diseases were the third most common global condition and the eighth leading cause of non-fatal health burden in 2021. Despite their high prevalence and substantial impact on quality of life, they remain relatively underprioritized in public health policy. This study aimed to examine long-term global trends and regional disparities in the burden of inflammatory and infectious skin diseases from 1990 to 2021. Patients and Methods: We conducted a cross-sectional analysis using data from the Global Burden of Disease (GBD) Study 2021. Age-standardized incidence rates, years lived with disability (YLDs), and average annual percentage change (AAPC) were assessed across 204 countries and territories, 21 global regions, and all age groups. Results: In 2021, skin and subcutaneous diseases ranked as the eighth leading cause of YLDs worldwide. Between 1990 and 2021, inflammatory skin diseases demonstrated a modest increase in incidence (AAPC 0.08%) and YLDs (0.04%). Infectious skin diseases showed a slightly greater rise in incidence (0.19%), whereas YLDs declined marginally (– 0.01%). The burden varied markedly by sociodemographic index (SDI) level and age, with the greatest impact observed among individuals younger than 20 years. Conclusion: Inflammatory and infectious skin diseases exhibit distinct global trajectories and disproportionate burdens across regions and age groups. These findings highlight the importance of context-specific prevention strategies, improved equity in health service delivery, and greater policy prioritization of skin disease management in global and national health agendas.