Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism
Atopic dermatitis (AD) is a globally prevalent chronic inflammatory skin disorder. Its pathogenesis remains incompletely understood, resulting in considerable therapeutic challenges. Recent studies have highlighted the significance of the interaction between AD and gut microbiome. In this study, we...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
|
| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2474256 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849687252163100672 |
|---|---|
| author | Hyejin Choi Min-Jin Kwak Youbin Choi An Na Kang Daye Mun Ju Young Eor Mi Ri Park Sangnam Oh Younghoon Kim |
| author_facet | Hyejin Choi Min-Jin Kwak Youbin Choi An Na Kang Daye Mun Ju Young Eor Mi Ri Park Sangnam Oh Younghoon Kim |
| author_sort | Hyejin Choi |
| collection | DOAJ |
| description | Atopic dermatitis (AD) is a globally prevalent chronic inflammatory skin disorder. Its pathogenesis remains incompletely understood, resulting in considerable therapeutic challenges. Recent studies have highlighted the significance of the interaction between AD and gut microbiome. In this study, we investigated the effects of probiotic-derived extracellular vesicles on AD. Initially, we isolated and characterized extracellular vesicles from Limosilactobacillus fermentum SLAM 216 (LF216EV) and characterized their composition through multi-omics analysis. Gene ontology (GO) and pathway analysis classified LF216EV proteins into biological processes, molecular functions, and cellular components. Importantly, specific abundance in linoleic, oleic, palmitic, sebacic, and stearic acids indicating upregulated fatty acid metabolism were observed by metabolomic analysis. Furthermore, featured lipid profiling including AcylGlcADG and ceramide were observed in LF216EV. Importantly, in an atopic dermatitis-like cell model induced by TNFα/IFNγ, LF216EV significantly modulated the expression of immune regulatory genes (TSLP, TNFα, IL-6, IL-1β, and MDC), indicating its potential functionality in atopic dermatitis. LF216EV alleviated AD-like phenotypes, such as redness, scaling/dryness, and excoriation, induced by DNCB. Histopathological analysis revealed that LF216EV decreased epidermal thickness and mast cell infiltration in the dermis. Furthermore, LF216EV administration reduced mouse scratching and depression-related behaviors, with a faster onset than the classical treatment with dexamethasone. In the quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we observed a significant increase in the expression levels of htrb2c, sert, and tph-1, genes associated with serotonin, in the skin and gut of the LF216EV-treated group, along with a significant increase in the total serum serotonin levels. Gut microbiome analysis of the LF216EV-treated group revealed an altered gut microbiota profile. Correlation analysis revealed that the genera Limosilactobacillus and Desulfovibrio were associated with differences in the intestinal metabolites, including serotonin. Our findings demonstrate that LF216EV mitigates AD-like symptoms by promoting serotonin synthesis through the modulation of gut microbiota and metabolome composition. |
| format | Article |
| id | doaj-art-6c8b297219424d49a0c4f0b7e8a0dbc3 |
| institution | DOAJ |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-6c8b297219424d49a0c4f0b7e8a0dbc32025-08-20T03:22:22ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2474256Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolismHyejin Choi0Min-Jin Kwak1Youbin Choi2An Na Kang3Daye Mun4Ju Young Eor5Mi Ri Park6Sangnam Oh7Younghoon Kim8Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul, KoreaDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul, KoreaDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul, KoreaDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul, KoreaDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul, KoreaDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul, KoreaFood Functionality Research Division, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, KoreaDepartment of Functional Food and Biotechnology, Jeonju University, Jeonju, KoreaDepartment of Agricultural Biotechnology and Research Institute of Agriculture and Life Science, Seoul National University, Seoul, KoreaAtopic dermatitis (AD) is a globally prevalent chronic inflammatory skin disorder. Its pathogenesis remains incompletely understood, resulting in considerable therapeutic challenges. Recent studies have highlighted the significance of the interaction between AD and gut microbiome. In this study, we investigated the effects of probiotic-derived extracellular vesicles on AD. Initially, we isolated and characterized extracellular vesicles from Limosilactobacillus fermentum SLAM 216 (LF216EV) and characterized their composition through multi-omics analysis. Gene ontology (GO) and pathway analysis classified LF216EV proteins into biological processes, molecular functions, and cellular components. Importantly, specific abundance in linoleic, oleic, palmitic, sebacic, and stearic acids indicating upregulated fatty acid metabolism were observed by metabolomic analysis. Furthermore, featured lipid profiling including AcylGlcADG and ceramide were observed in LF216EV. Importantly, in an atopic dermatitis-like cell model induced by TNFα/IFNγ, LF216EV significantly modulated the expression of immune regulatory genes (TSLP, TNFα, IL-6, IL-1β, and MDC), indicating its potential functionality in atopic dermatitis. LF216EV alleviated AD-like phenotypes, such as redness, scaling/dryness, and excoriation, induced by DNCB. Histopathological analysis revealed that LF216EV decreased epidermal thickness and mast cell infiltration in the dermis. Furthermore, LF216EV administration reduced mouse scratching and depression-related behaviors, with a faster onset than the classical treatment with dexamethasone. In the quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we observed a significant increase in the expression levels of htrb2c, sert, and tph-1, genes associated with serotonin, in the skin and gut of the LF216EV-treated group, along with a significant increase in the total serum serotonin levels. Gut microbiome analysis of the LF216EV-treated group revealed an altered gut microbiota profile. Correlation analysis revealed that the genera Limosilactobacillus and Desulfovibrio were associated with differences in the intestinal metabolites, including serotonin. Our findings demonstrate that LF216EV mitigates AD-like symptoms by promoting serotonin synthesis through the modulation of gut microbiota and metabolome composition.https://www.tandfonline.com/doi/10.1080/19490976.2025.2474256Atopic dermatitisgut-skin axisextracellular vesiclegut microbiomemulti-omics analysis |
| spellingShingle | Hyejin Choi Min-Jin Kwak Youbin Choi An Na Kang Daye Mun Ju Young Eor Mi Ri Park Sangnam Oh Younghoon Kim Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism Gut Microbes Atopic dermatitis gut-skin axis extracellular vesicle gut microbiome multi-omics analysis |
| title | Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism |
| title_full | Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism |
| title_fullStr | Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism |
| title_full_unstemmed | Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism |
| title_short | Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism |
| title_sort | extracellular vesicles of limosilactobacillus fermentum slam216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism |
| topic | Atopic dermatitis gut-skin axis extracellular vesicle gut microbiome multi-omics analysis |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2474256 |
| work_keys_str_mv | AT hyejinchoi extracellularvesiclesoflimosilactobacillusfermentumslam216ameliorateskinsymptomsofatopicdermatitisbyregulatinggutmicrobiomeonserotoninmetabolism AT minjinkwak extracellularvesiclesoflimosilactobacillusfermentumslam216ameliorateskinsymptomsofatopicdermatitisbyregulatinggutmicrobiomeonserotoninmetabolism AT youbinchoi extracellularvesiclesoflimosilactobacillusfermentumslam216ameliorateskinsymptomsofatopicdermatitisbyregulatinggutmicrobiomeonserotoninmetabolism AT annakang extracellularvesiclesoflimosilactobacillusfermentumslam216ameliorateskinsymptomsofatopicdermatitisbyregulatinggutmicrobiomeonserotoninmetabolism AT dayemun extracellularvesiclesoflimosilactobacillusfermentumslam216ameliorateskinsymptomsofatopicdermatitisbyregulatinggutmicrobiomeonserotoninmetabolism AT juyoungeor extracellularvesiclesoflimosilactobacillusfermentumslam216ameliorateskinsymptomsofatopicdermatitisbyregulatinggutmicrobiomeonserotoninmetabolism AT miripark extracellularvesiclesoflimosilactobacillusfermentumslam216ameliorateskinsymptomsofatopicdermatitisbyregulatinggutmicrobiomeonserotoninmetabolism AT sangnamoh extracellularvesiclesoflimosilactobacillusfermentumslam216ameliorateskinsymptomsofatopicdermatitisbyregulatinggutmicrobiomeonserotoninmetabolism AT younghoonkim extracellularvesiclesoflimosilactobacillusfermentumslam216ameliorateskinsymptomsofatopicdermatitisbyregulatinggutmicrobiomeonserotoninmetabolism |