{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:09:10Z","timestamp":1779253750532,"version":"3.51.4"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Common variable immunodeficiency (CVID) is associated with bacterial dysbiosis, particularly in patients with immune dysregulation, but the contribution of the fungal microbiome (mycobiome) remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a cross-sectional, multi-compartment study in 41 adults with CVID (24 with immune dysregulation, dCVID; 17 with infectious-only manifestations, iCVID) and 15 matched healthy controls. Saliva, sputum and stool samples were analyzed using ITS1 amplicon sequencing with amplicon sequence variant-based taxonomic assignment, followed by \u03b1\/\u03b2-diversity analyses, multivariate modeling, differential abundance testing and machine learning approaches for biomarker identification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across all three niches, mycobiome composition differed significantly between CVID and controls, whereas dCVID and iCVID did not separate. Fungal richness and evenness were reduced in CVID, most prominently in respiratory and oral samples. ANCOM-BC revealed a reproducible \u201c\n                      <jats:italic>Candida<\/jats:italic>\n                      -skewed\u201d configuration in both phenotypes, with marked enrichment of\n                      <jats:italic>Candida albicans<\/jats:italic>\n                      in sputum, stool and saliva, accompanied by increased abundance of other opportunistic yeasts such as\n                      <jats:italic>Nakaseomyces glabratus<\/jats:italic>\n                      . In contrast, environmental or putatively commensal taxa were consistently depleted. Random forest models based on fungal profiles accurately discriminated CVID from controls, with AUC up to 0.96 (95% CI 0.91-0.99) in saliva and 0.94 (95% CI 0.88-0.99) in stool, whereas classification of dCVID versus iCVID was modest.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Together, these findings provide the first integrated view of mycobiome alterations across multiple ecological niches in CVID, highlighting consistent enrichment of opportunistic yeasts over commensals. The expansion of\n                      <jats:italic>C. albicans<\/jats:italic>\n                      supports a potential pathobiont role, and the strong discriminatory performance of fungal signatures underscores their promise as non-invasive biomarkers in this immunodeficiency.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1804724","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:37:43Z","timestamp":1779251863000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiniche mycobiome profiling identifies distinctive fungal dysbiosis in common variable immunodeficiency"],"prefix":"10.3389","volume":"17","author":[{"given":"Marta Dafne","family":"Cabanero-Navalon","sequence":"first","affiliation":[{"name":"Primary Immune Deficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe","place":["Valencia, Spain"]},{"name":"Research Group of Chronic Diseases and HIV Infection, Health Research Institute La Fe","place":["Valencia, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Carda-Di\u00e9guez","sequence":"additional","affiliation":[{"name":"Genomics & Health Department, Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica de la Comunitat Valenciana (FISABIO) Foundation","place":["Valencia, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Mira","sequence":"additional","affiliation":[{"name":"Genomics & Health Department, Fundaci\u00f3n para el Fomento de la Investigaci\u00f3n Sanitaria y Biom\u00e9dica de la Comunitat Valenciana (FISABIO) Foundation","place":["Valencia, Spain"]},{"name":"CIBER Center for Epidemiology and Public Health (CIBER-ESP)","place":["Madrid, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Moral Moral","sequence":"additional","affiliation":[{"name":"Primary Immune Deficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe","place":["Valencia, Spain"]},{"name":"Research Group of Chronic Diseases and HIV Infection, Health Research Institute La Fe","place":["Valencia, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Mercedes","family":"Diaz Luna","sequence":"additional","affiliation":[{"name":"Primary Immune Deficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe","place":["Valencia, Spain"]},{"name":"Research Group of Chronic Diseases and HIV Infection, Health Research Institute La Fe","place":["Valencia, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9ctor","family":"Balastegui-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Primary Immune Deficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe","place":["Valencia, Spain"]},{"name":"Research Group of Chronic Diseases and HIV Infection, Health Research Institute La Fe","place":["Valencia, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Salavert Llet\u00ed","sequence":"additional","affiliation":[{"name":"Severe Infection Research Group, Health Research Institute La Fe","place":["Valencia, Spain"]},{"name":"Unit of Infectious Diseases, University and Polytechnic Hospital La Fe","place":["Valencia, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Garcia-Bustos","sequence":"additional","affiliation":[{"name":"Primary Immune Deficiencies Unit, Department of Internal Medicine, University and Polytechnic Hospital La Fe","place":["Valencia, Spain"]},{"name":"Severe Infection Research Group, Health Research Institute La Fe","place":["Valencia, Spain"]},{"name":"University Institute of Animal Health and Food Safety (IUSA), University of Las Palmas de Gran Canaria","place":["Arucas, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1007\/s10875-017-0464-9","article-title":"International union of immunological societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity","volume":"38","author":"Picard","year":"2018","journal-title":"J ClinImmunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-377945","article-title":"Morbidity and mortality in common variable immune deficiency over 4 decades","volume":"119","author":"Resnick","year":"2012","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02753","article-title":"Current understanding and recent developments in common variable immunodeficiency associated autoimmunity","volume":"10","author":"Gereige","year":"2019","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1146\/annurev-pathmechdis-031521-024229","article-title":"Common variable immunodeficiency: more pathways than roads to Rome","volume":"18","author":"Peng","year":"2023","journal-title":"Annu Rev Pathol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-018-0574-z","article-title":"Autoimmunity and inflammation in CVID: a possible crosstalk between immune activation, gut microbiota, and epigenetic modifications","volume":"39","author":"J\u00f8rgensen","year":"2019","journal-title":"J ClinImmunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.11.008","article-title":"Microbial dysbiosis in common variable immune deficiencies: evidence, causes, and consequences","volume":"38","author":"Berbers","year":"2017","journal-title":"Trends Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.18","article-title":"Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation","volume":"9","author":"J\u00f8rgensen","year":"2016","journal-title":"Mucosal Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2015-0250PS","article-title":"The gut-liver-lung axis. Modulation of the innate immune response and its possible role in chronic obstructive pulmonary disease","volume":"54","author":"Young","year":"2016","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.712915","article-title":"Gut microbiome and common variable immunodeficiency: few certainties and many outstanding questions","volume":"12","author":"Varricchi","year":"2021","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s12929-019-0537-6","article-title":"Host-microbe interactions in the pathogenesis and clinical course of sarcoidosis","volume":"26","author":"Inaoka","year":"2019","journal-title":"J BioMed Sci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9050932","article-title":"The role of lung colonization in connective tissue disease-associated interstitial lung disease","volume":"9","author":"Ricci","year":"2021","journal-title":"Microorganisms"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2023.109796","article-title":"Dysimmunity in common variable immunodeficiency is associated with alterations in oral, respiratory, and intestinal microbiota","volume":"256","author":"Cabanero-Navalon","year":"2023","journal-title":"Clin Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12102239","article-title":"Linking microbiota profiles to disease characterization in common variable immunodeficiency: the case of granulomatous-lymphocytic interstitial lung disease","volume":"12","author":"Cabanero-Navalon","year":"2024","journal-title":"Biomedicines"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2089002","DOI":"10.1080\/19490976.2022.2089002","article-title":"Interactions among the mycobiome, bacteriome, inflammation, and diet in people living with HIV","volume":"14","author":"Gosalbes","year":"2022","journal-title":"Gut. Microbes"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1015775","article-title":"Neglected mycobiome in HIV infection: alterations, common fungal diseases and antifungal immunity","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04502-w","article-title":"Immune regulation by fungal strain diversity in inflammatory bowel disease","volume":"603","author":"Li","year":"2022","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-022-00515-w","article-title":"Molding\u201d immunity\u2014modulation of mucosal and systemic immunity by the intestinal mycobiome in health and disease","volume":"15","author":"Gutierrez","year":"2022","journal-title":"Mucosal Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.18176\/jiaci.0231","article-title":"Circulating helper T-cell subsets and regulatory T cells in patients with common variable immunodeficiency without known monogenic disease","volume":"28","author":"Azizi","year":"2018","journal-title":"J Investig Allergol. Clin Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00174","article-title":"Follicular T cells from smB- common variable immunodeficiency patients are skewed toward a Th1 phenotype","volume":"8","author":"Cunill","year":"2017","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01914","article-title":"Bacterial but not fungal gut microbiota alterations are associated with common variable immunodeficiency (CVID) phenotype","volume":"10","author":"Fiedorov\u00e1","year":"2019","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-124545","article-title":"Common variable immunodeficiency disorders: division into distinct clinical phenotypes","volume":"112","author":"Chapel","year":"2008","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","first-page":"16829","DOI":"10.1038\/s41598-018-35165-1","article-title":"Author correction: Multiple approaches detect the presence of fungi in human breastmilk samples from healthy mothers","volume":"8","author":"Boix-Amor\u00f3s","year":"2018","journal-title":"Sci Rep"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040863","article-title":"High-coverage ITS primers for the DNA-based identification of ascomycetes and basidiomycetes in environmental samples","volume":"7","author":"Toju","year":"2012","journal-title":"PloS One"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr507","article-title":"FLASH: fast length adjustment of short reads to improve genome assemblies","volume":"27","author":"Magoc","year":"2011","journal-title":"Bioinformatics"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr026","article-title":"Quality control and preprocessing of metagenomic datasets","volume":"27","author":"Schmieder","year":"2011","journal-title":"Bioinformatics"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr381","article-title":"UCHIME improves sensitivity and speed of chimera detection","volume":"27","author":"Edgar","year":"2011","journal-title":"Bioinformatics"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: High-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat Methods"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1039","article-title":"The UNITE database for molecular identification and taxonomic communication of fungi and other eukaryotes: sequences, taxa and classifications reconsidered","volume":"52","author":"Abarenkov","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"B29","doi-asserted-by":"publisher","first-page":"3514","DOI":"10.1038\/s41467-020-17041-7","article-title":"Analysis of compositions of microbiomes with bias correction","volume":"11","author":"Lin","year":"2020","journal-title":"Nat Commun"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.716493","article-title":"Bacterial composition and metabolomics of dental plaque from adolescents","volume":"11","author":"Havsed","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005752","article-title":"mixOmics: An R package for 'omics feature selection and multiple data integration","volume":"13","author":"Rohart","year":"2017","journal-title":"PloS Comput Biol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40168-024-01982-y","article-title":"Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation","volume":"13","author":"Berbers","year":"2025","journal-title":"Microbiome"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-023-01469-9","article-title":"Fecal immunoglobulin levels as a modifier of the gut microbiome in patients with common variable immunodeficiency","volume":"43","author":"N\u00f6ltner","year":"2023","journal-title":"J ClinImmunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.900055","article-title":"Evaluation of the 10 warning signs in primary and secondary immunodeficient patients","volume":"13","author":"Eldeniz","year":"2022","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1080\/20002297.2016.1270613","article-title":"Candida albicans alters the bacterial microbiome of early in vitro oral biofilms","volume":"9","author":"Janus","year":"2017","journal-title":"J Oral Microbiol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14186418","article-title":"Correlation between fungal and bacterial populations in periodontitis through targeted sequencing: a pilot study","volume":"14","author":"Ayers","year":"2025","journal-title":"J Clin Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdent.2025.106119","article-title":"Oraltypes of the human oral bacteriome and mycobiome","volume":"163","author":"Wang","year":"2025","journal-title":"J Dent"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1804724\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:37:47Z","timestamp":1779251867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1804724\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":37,"alternative-id":["10.3389\/fimmu.2026.1804724"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1804724","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"article-number":"1804724"}}