Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acid
Abstract Background 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 bet...
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BMC
2025-05-01
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| Series: | Microbiome |
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| Online Access: | https://doi.org/10.1186/s40168-025-02102-0 |
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| author | Qingrong Ni Lin Xia Ye Huang Xiaoying Yuan Weijie Gu Yueqi Chen Yijin Wang Meng Nian Shengxi Wu Hong Cai Jing Huang |
| author_facet | Qingrong Ni Lin Xia Ye Huang Xiaoying Yuan Weijie Gu Yueqi Chen Yijin Wang Meng Nian Shengxi Wu Hong Cai Jing Huang |
| author_sort | Qingrong Ni |
| collection | DOAJ |
| description | Abstract Background 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. Results 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). Conclusions 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. Video Abstract |
| format | Article |
| id | doaj-art-6eb861722c4644449d8ef4ea31d78d84 |
| institution | DOAJ |
| issn | 2049-2618 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj-art-6eb861722c4644449d8ef4ea31d78d842025-08-20T03:09:20ZengBMCMicrobiome2049-26182025-05-0113111910.1186/s40168-025-02102-0Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acidQingrong Ni0Lin Xia1Ye Huang2Xiaoying Yuan3Weijie Gu4Yueqi Chen5Yijin Wang6Meng Nian7Shengxi Wu8Hong Cai9Jing Huang10Department of Dermatology, Air Force Medical Center, Fourth Military Medical UniversityDepartment of Cardiovascular Surgery, General Hospital of Northern Theater CommandDepartment of Dermatology, Air Force Medical Center, Fourth Military Medical UniversityDepartment of Dermatology, Air Force Medical Center, Fourth Military Medical UniversityDepartment of Dermatology, Air Force Medical Center, Fourth Military Medical UniversityDepartment of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Dermatology, Air Force Medical Center, Fourth Military Medical UniversityDepartment of Neurobiology, Basic Medical Science Academy, Fourth Military Medical UniversityDepartment of Neurobiology, Basic Medical Science Academy, Fourth Military Medical UniversityDepartment of Dermatology, Air Force Medical Center, Fourth Military Medical UniversityDepartment of Neurobiology, Basic Medical Science Academy, Fourth Military Medical UniversityAbstract Background 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. Results 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). Conclusions 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. Video Abstracthttps://doi.org/10.1186/s40168-025-02102-0Gut microbiotaVitiligoOxidative stressHippuric acid |
| spellingShingle | Qingrong Ni Lin Xia Ye Huang Xiaoying Yuan Weijie Gu Yueqi Chen Yijin Wang Meng Nian Shengxi Wu Hong Cai Jing Huang Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acid Microbiome Gut microbiota Vitiligo Oxidative stress Hippuric acid |
| title | Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acid |
| title_full | Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acid |
| title_fullStr | Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acid |
| title_full_unstemmed | Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acid |
| title_short | Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acid |
| title_sort | gut microbiota dysbiosis orchestrates vitiligo related oxidative stress through the metabolite hippuric acid |
| topic | Gut microbiota Vitiligo Oxidative stress Hippuric acid |
| url | https://doi.org/10.1186/s40168-025-02102-0 |
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