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Fungal Dysbiosis and Intestinal Inflammation in Children With Beta-Cell Autoimmunity

Terhi Ruohtula; Christopher L. Fogarty; Janne J. Koskimäki; Daniel Muthas; Anna Maria Pirttilä; Anton Lavrinienko; Laura Orivuori; Jorma Ilonen; Outi Vaarala; Kristiina Luopajärvi; Jarno Honkanen; Taina Härkönen; Mysore Vishakante Gowda Tejesvi; Mikael Knip; Arja Vuorela

dc.contributor.authorTerhi Ruohtula
dc.contributor.authorChristopher L. Fogarty
dc.contributor.authorJanne J. Koskimäki
dc.contributor.authorDaniel Muthas
dc.contributor.authorAnna Maria Pirttilä
dc.contributor.authorAnton Lavrinienko
dc.contributor.authorLaura Orivuori
dc.contributor.authorJorma Ilonen
dc.contributor.authorOuti Vaarala
dc.contributor.authorKristiina Luopajärvi
dc.contributor.authorJarno Honkanen
dc.contributor.authorTaina Härkönen
dc.contributor.authorMysore Vishakante Gowda Tejesvi
dc.contributor.authorMikael Knip
dc.contributor.authorArja Vuorela
dc.date.accessioned2022-10-27T12:27:10Z
dc.date.available2022-10-27T12:27:10Z
dc.identifier.urihttps://www.utupub.fi/handle/10024/158693
dc.description.abstractAlthough gut bacterial dysbiosis is recognized as a regulator of beta-cell autoimmunity, no data is available on fungal dysbiosis in the children at the risk of type 1 diabetes (T1D). We hypothesized that the co-occurrence of fungal and bacterial dysbiosis contributes to the intestinal inflammation and autoimmune destruction of insulin-producing beta-cells in T1D. Fecal and blood samples were collected from 26 children tested positive for at least one diabetes-associated autoantibody (IAA, GADA, IA-2A or ICA) and matched autoantibody-negative children with HLA-conferred susceptibility to T1D (matched for HLA-DQB1 haplotype, age, gender and early childhood nutrition). Bacterial 16S and fungal ITS2 sequencing, and analyses of the markers of intestinal inflammation, namely fecal human beta-defensin-2 (HBD2), calprotectin and secretory total IgA, were performed. Anti-Saccharomyces cerevisiae antibodies (ASCA) and circulating cytokines, IFNG, IL-17 and IL-22, were studied. After these analyses, the children were followed for development of clinical T1D (median 8 years and 8 months). Nine autoantibody positive children were diagnosed with T1D, whereas none of the autoantibody negative children developed T1D during the follow-up. Fungal dysbiosis, characterized by high abundance of fecal Saccharomyces and Candida, was found in the progressors, i.e., children with beta-cell autoimmunity who during the follow-up progressed to clinical T1D. These children showed also bacterial dysbiosis, i.e., increased Bacteroidales and Clostridiales ratio, which was, however, found also in the non-progressors, and is thus a common nominator in the children with beta-cell autoimmunity. Furthermore, the progressors showed markers of intestinal inflammation detected as increased levels of fecal HBD2 and ASCA IgG to fungal antigens. We conclude that the fungal and bacterial dysbiosis, and intestinal inflammation are associated with the development of T1D in children with beta-cell autoimmunity.
dc.language.isoen
dc.publisherFRONTIERS MEDIA SA
dc.titleFungal Dysbiosis and Intestinal Inflammation in Children With Beta-Cell Autoimmunity
dc.identifier.urnURN:NBN:fi-fe2021042823848
dc.relation.volume11
dc.contributor.organizationfi=biolääketieteen laitos, yhteiset|en=Institute of Biomedicine|
dc.contributor.organization-code2607100
dc.converis.publication-id46996218
dc.converis.urlhttps://research.utu.fi/converis/portal/Publication/46996218
dc.identifier.eissn1664-3224
dc.identifier.jour-issn1664-3224
dc.okm.affiliatedauthorIlonen, Jorma
dc.okm.discipline3121 Internal medicineen_GB
dc.okm.discipline3121 Sisätauditfi_FI
dc.okm.internationalcopublicationinternational co-publication
dc.okm.internationalityInternational publication
dc.okm.typeJournal article
dc.publisher.countrySveitsifi_FI
dc.publisher.countrySwitzerlanden_GB
dc.publisher.country-codeCH
dc.relation.articlenumberARTN 468
dc.relation.doi10.3389/fimmu.2020.00468
dc.relation.ispartofjournalFrontiers in Immunology
dc.year.issued2020


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