{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:05:48Z","timestamp":1789506348169,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Catholic Medical Center Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vitiligo is an autoimmune skin disease with a significant psychological burden and complex pathogenesis. While genetic factors contribute approximately 30% to its development, recent evidence suggests a crucial role of the gut microbiome in autoimmune diseases. This study investigated differences in gut microbiome composition and metabolic pathways between active spreading vitiligo patients and healthy controls using shotgun whole-genome sequencing in a Korean cohort. Taxonomic profiling reveals distinct characteristics in microbial community structure, with vitiligo patients showing an imbalanced proportion dominated by Actinomycetota and Bacteroidota. The vitiligo group exhibited significantly reduced abundance of specific species including Faecalibacterium prausnitzii, Faecalibacteriumduncaniae, and Meamonas funiformis, and increased Bifidobacterium bifidum compared to healthy controls. Metabolic pathway analysis identified significant enrichment in O-glycan biosynthesis pathways in vitiligo patients, while healthy controls showed enrichment in riboflavin metabolism and bacterial chemotaxis pathways. These findings provide new insights into the gut\u2013skin axis in vitiligo pathogenesis and suggest potential therapeutic targets through microbiota modulation.<\/jats:p>","DOI":"10.3390\/ijms26072939","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T12:01:50Z","timestamp":1742817710000},"page":"2939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of Gut Microbiota in Patients with Active Spreading Vitiligo Based on Whole-Genome Shotgun Sequencing"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2711-3112","authenticated-orcid":false,"given":"Hyun Jeong","family":"Ju","sequence":"first","affiliation":[{"name":"Department of Dermatology, St. Vincent\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 16247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Hyun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8158-1884","authenticated-orcid":false,"given":"Ji Hae","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Vincent\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 16247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-1627","authenticated-orcid":false,"given":"Ji Hae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Vincent\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 16247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Min","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Dermatology, St. Vincent\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 16247, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8642-2479","authenticated-orcid":false,"given":"Young Bok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Uijeongbu St. Mary\u2019s Hospital, The Catholic University of Korea, Seoul 11765, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0168-9546","authenticated-orcid":false,"given":"Minho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/S0140-6736(14)60763-7","article-title":"Vitiligo","volume":"386","author":"Ezzedine","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1007\/s13555-023-01001-2","article-title":"Comorbidity Burden Among Patients with Vitiligo in the United States: A Large-Scale Retrospective Claims Database Analysis","volume":"13","author":"Ezzedine","year":"2023","journal-title":"Dermatol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jid.2020.06.004","article-title":"The Genetic Basis of Vitiligo","volume":"141","author":"Spritz","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bhutta, N.K., Xu, X., Jian, C., Wang, Y., Liu, Y., Sun, J., Han, B., Wu, S., and Javeed, A. (2024). Gut microbiota mediated T cells regulation and autoimmune diseases. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1477187"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mousa, W.K., Chehadeh, F., and Husband, S. (2022). Microbial dysbiosis in the gut drives systemic autoimmune diseases. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.906258"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Oliveira, G.L.V.d. (2019). The Gut Microbiome in Autoimmune Diseases. Microbiome and Metabolome in Diagnosis, Therapy, and Other Strategic Applications, Academic Press.","DOI":"10.1016\/B978-0-12-815249-2.00033-6"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Luan, M., Niu, M., Yang, P., Han, D., Zhang, Y., Li, W., He, Q., Zhao, Y., Mao, B., and Chen, J. (2023). Metagenomic sequencing reveals altered gut microbial compositions and gene functions in patients with non-segmental vitiligo. BMC Microbiol., 23.","DOI":"10.1186\/s12866-023-03020-7"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1016\/j.jid.2021.01.036","article-title":"Analysis of Matched Skin and Gut Microbiome of Patients with Vitiligo Reveals Deep Skin Dysbiosis: Link with Mitochondrial and Immune Changes","volume":"141","author":"Bzioueche","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ganju, P., Nagpal, S., Mohammed, M.H., Nishal Kumar, P., Pandey, R., Natarajan, V.T., Mande, S.S., and Gokhale, R.S. (2016). Microbial community profiling shows dysbiosis in the lesional skin of Vitiligo subjects. Sci. Rep., 6.","DOI":"10.1038\/srep18761"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jid.2019.08.435","article-title":"Antibiotics Drive Microbial Imbalance and Vitiligo Development in Mice","volume":"140","author":"Dellacecca","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"T505","DOI":"10.1016\/j.ad.2024.03.003","article-title":"[Translated article] Quantification of the Progression Rate in Vitiligo and Prognostic Implications","volume":"115","year":"2024","journal-title":"Actas Dermosifiliogr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bars-Cortina, D., Ramon, E., Rius-Sansalvador, B., Guin\u00f3, E., Garcia-Serrano, A., Mach, N., Khannous-Lleiffe, O., Saus, E., Gabald\u00f3n, T., and Ib\u00e1\u00f1ez-Sanz, G. (2024). Comparison between 16S rRNA and shotgun sequencing in colorectal cancer, advanced colorectal lesions, and healthy human gut microbiota. BMC Genom., 25.","DOI":"10.1186\/s12864-024-10621-7"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.chom.2019.01.019","article-title":"Virome Diversity Correlates with Intestinal Microbiome Diversity in Adult Monozygotic Twins","volume":"25","author":"Chou","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/nature09199","article-title":"Viruses in the fecal microbiota of monozygotic twins and their mothers","volume":"466","author":"Reyes","year":"2010","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jaut.2017.03.009","article-title":"Integration of microbiome and epigenome to decipher the pathogenesis of autoimmune diseases","volume":"83","author":"Chen","year":"2017","journal-title":"J. Autoimmun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.4049\/jimmunol.1200042","article-title":"IL-10 regulates Il12b expression via histone deacetylation: Implications for intestinal macrophage homeostasis","volume":"189","author":"Kobayashi","year":"2012","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Brown, J., Robusto, B., and Morel, L. (2020). Intestinal Dysbiosis and Tryptophan Metabolism in Autoimmunity. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01741"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1172\/JCI32639","article-title":"Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis","volume":"118","author":"Joosten","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1002\/art.39783","article-title":"Dysbiosis Contributes to Arthritis Development via Activation of Autoreactive T Cells in the Intestine","volume":"68","author":"Maeda","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s12016-012-8344-9","article-title":"Anti-Saccharomyces cerevisiae autoantibodies in autoimmune diseases: From bread baking to autoimmunity","volume":"45","author":"Rinaldi","year":"2013","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ni, Q., Ye, Z., Wang, Y., Chen, J., Zhang, W., Ma, C., Li, K., Liu, Y., Liu, L., and Han, Z. (2020). Gut Microbial Dysbiosis and Plasma Metabolic Profile in Individuals With Vitiligo. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.592248"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1128\/JCM.01500-13","article-title":"Increased Proportions of Bifidobacterium and the Lactobacillus Group and Loss of Butyrate-Producing Bacteria in Inflammatory Bowel Disease","volume":"52","author":"Wang","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100046","DOI":"10.1016\/j.bbii.2024.100046","article-title":"Influence of gut microbiota on autoimmunity: A narrative review","volume":"5","author":"Sai","year":"2024","journal-title":"Brain Behav. Immun. Integr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/ismej.2016.176","article-title":"Faecalibacterium prausnitzii: From microbiology to diagnostics and prognostics","volume":"11","author":"Duncan","year":"2017","journal-title":"ISME J."},{"key":"ref_25","first-page":"1","article-title":"Exploring the relationship between Faecalibacterium duncaniae and Escherichia coli in inflammatory bowel disease (IBD): Insights and implications","volume":"23","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Verstraeten, S., Layec, S., Auger, S., Juste, C., Henry, C., Charif, S., Jaszczyszyn, Y., Sokol, H., Beney, L., and Langella, P. (2024). Faecalibacterium duncaniae A2-165 regulates the expression of butyrate synthesis, ferrous iron uptake, and stress-response genes based on acetate consumption. Sci. Rep., 14.","DOI":"10.1038\/s41598-023-51059-3"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chollet, L., Heumel, S., Deruyter, L., Bouilloux, F., Delval, L., Robert, V., Gevaert, M.-H., Pichavant, M., Sencio, V., and Robil, C. (2024). Faecalibacterium duncaniae as a novel next generation probiotic against influenza. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1347676"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Shimizu, J., Kubota, T., Takada, E., Takai, K., Fujiwara, N., Arimitsu, N., Ueda, Y., Wakisaka, S., Suzuki, T., and Suzuki, N. (2016). Bifidobacteria Abundance-Featured Gut Microbiota Compositional Change in Patients with Behcet\u2019s Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153746"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Nugumanova, G., Ponomarev, E.D., Askarova, S., Fasler-Kan, E., and Barteneva, N.S. (2023). Freshwater Cyanobacterial Toxins, Cyanopeptides and Neurodegenerative Diseases. Toxins, 15.","DOI":"10.20944\/preprints202301.0357.v1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/s41385-019-0154-4","article-title":"Helicobacter suis infection alters glycosylation and decreases the pathogen growth inhibiting effect and binding avidity of gastric mucins","volume":"12","author":"Padra","year":"2019","journal-title":"Mucosal Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.vetmic.2012.06.031","article-title":"An experimental Helicobacter suis infection causes gastritis and reduced daily weight gain in pigs","volume":"160","author":"Flahou","year":"2012","journal-title":"Vet. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3382\/ps\/pez460","article-title":"Effects of Paenibacillus xylanexedens on growth performance, intestinal histomorphology, intestinal microflora, and immune response in broiler chickens challenged with Escherichia coli K88","volume":"99","author":"Ekim","year":"2020","journal-title":"Poult. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.ebiom.2019.09.008","article-title":"Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasis","volume":"48","author":"Yamada","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/s41423-023-01074-1","article-title":"Immune regulatory networks coordinated by glycans and glycan-binding proteins in autoimmunity and infection","volume":"10","author":"Pinho","year":"2023","journal-title":"Cell. Mol. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.cell.2017.11.041","article-title":"Engineered Sialylation of Pathogenic Antibodies In Vivo Attenuates Autoimmune Disease","volume":"172","author":"Pagan","year":"2018","journal-title":"Cell"},{"key":"ref_36","first-page":"285","article-title":"In Riboflavin metabolism: Role in mitochondrial function","volume":"4","author":"Balasubramaniam","year":"2020","journal-title":"J. Transl. Genet. Genom."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.2174\/092986710793205462","article-title":"Emerging roles for riboflavin in functional rescue of mitochondrial \u03b2-oxidation flavoenzymes","volume":"17","author":"Henriques","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e1810","DOI":"10.1002\/ctm2.1810","article-title":"Vitiligo auto-immune response upon oxidative stress-related mitochondrial DNA release opens up new therapeutic strategies","volume":"14","author":"Botton","year":"2024","journal-title":"Clin. Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Papaccio, F., Bellei, B., Ottaviani, M., D\u2019Arino, A., Truglio, M., Caputo, S., Cigliana, G., Sciuto, L., Migliano, E., and Pacifico, A. (2022). A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPAR\u03b3 Agonist. Cells, 11.","DOI":"10.3390\/cells11223583"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.bbrc.2015.12.083","article-title":"Analysis of the microbiome: Advantages of whole genome shotgun versus 16S amplicon sequencing","volume":"469","author":"Ranjan","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1089\/omi.2018.0013","article-title":"Quantitative Assessment of Shotgun Metagenomics and 16S rDNA Amplicon Sequencing in the Study of Human Gut Microbiome","volume":"22","author":"Laudadio","year":"2018","journal-title":"Omics"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Durazzi, F., Sala, C., Castellani, G., Manfreda, G., Remondini, D., and De Cesare, A. (2021). Comparison between 16S rRNA and shotgun sequencing data for the taxonomic characterization of the gut microbiota. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-82726-y"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/nature25973","article-title":"Environment dominates over host genetics in shaping human gut microbiota","volume":"555","author":"Rothschild","year":"2018","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kim, J., Park, K.Y., Park, H.K., Hwang, H.S., Seo, M.R., Kim, B., Cho, Y., Rho, M., and Pai, H. (2021). High fecal carriage of bla(CTX-M), bla(CMY-2), and plasmid-mediated quinolone resistance genes among healthy Korean people in a metagenomic analysis. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-84974-4"},{"key":"ref_45","unstructured":"Joshi, N., and Fass, J. (2025, March 19). Sickle: A Sliding-Window, Adaptive, Quality-Based Trimming Tool for FastQ Files (Version 1.33) [Software]. Available online: https:\/\/github.com\/najoshi\/sickle."},{"key":"ref_46","unstructured":"Li, H. (2013). Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wood, D.E., Lu, J., and Langmead, B. (2019). Improved metagenomic analysis with Kraken 2. Genome Biol., 20.","DOI":"10.1186\/s13059-019-1891-0"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wood, D.E., and Salzberg, S.L. (2014). Kraken: Ultrafast metagenomic sequence classification using exact alignments. Genome Biol., 15.","DOI":"10.1186\/gb-2014-15-3-r46"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2307\/1218190","article-title":"Evolution and measurement of species diversity","volume":"21","author":"Whittaker","year":"1972","journal-title":"Taxon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s004420100716","article-title":"Ecologically meaningful transformations for ordination of species data","volume":"129","author":"Legendre","year":"2001","journal-title":"Oecologia"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Abubucker, S., Segata, N., Goll, J., Schubert, A.M., Izard, J., Cantarel, B.L., Rodriguez-Mueller, B., Zucker, J., Thiagarajan, M., and Henrissat, B. (2012). Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLoS Comput. Biol., 8.","DOI":"10.1371\/journal.pcbi.1002358"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/s41592-018-0176-y","article-title":"Species-level functional profiling of metagenomes and metatranscriptomes","volume":"15","author":"Franzosa","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kumar, S., Mahajan, S., Kale, D., Chourasia, N., Khan, A., Asati, D., Kotnis, A., and Sharma, V.K. (2024). Insights into the gut microbiome of vitiligo patients from India. BMC Microbiol., 24.","DOI":"10.1186\/s12866-024-03529-5"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e904","DOI":"10.1111\/jdv.19012","article-title":"Alterations of gut microbiota and gut metabolites in the young-adult vitiligo patients","volume":"37","author":"Wu","year":"2023","journal-title":"J. Eur. Acad. Dermatol. Venereol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/2939\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:59:15Z","timestamp":1760029155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/2939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,24]]},"references-count":54,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26072939"],"URL":"https:\/\/doi.org\/10.3390\/ijms26072939","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,24]]}}}