Fungal Dysbiosis and Intestinal Inflammation in Children With Beta-Cell Autoimmunity
Honkanen, J., Vuorela, A., Muthas, D., Orivuori, L., Luopajärvi, K., Tejesvi, M. V. G., Lavrinienko, A., Pirttilä, A. M., Fogarty, C. L., Härkönen, T., Ilonen, J., Ruohtula, T., Knip, M., Koskimäki, J. J., & Vaarala, O. (2020). Fungal Dysbiosis and Intestinal Inflammation in Children With Beta-Cell Autoimmunity. Frontiers in Immunology, . https://doi.org/10.3389/fimmu.2020.00468
Published inFrontiers in Immunology
© 2020 the Authors
Although 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. ...
Publication in research information system
MetadataShow full item record
Additional information about fundingThis work was supported by the Finnish Cultural Foundation (JH), the Finnish Diabetes Research Foundation (JH and OV), the Academy of Finland (OV), the Päivikki and Sakari Sohlberg Foundation (OV), and European Foundation for the Study of Diabetes (OV).
Showing items with similar title or keywords.
Vascular Adhesion Protein 1 Mediates Gut Microbial Flagellin-Induced Inflammation, Leukocyte Infiltration, and Hepatic Steatosis Toivonen, Raine; Vanhatalo, Sanja; Hollmén, Maija; Munukka, Eveliina; Keskitalo, Anniina; Pietilä, Sami; Elo, Laura; Huovinen, Pentti; Jalkanen, Sirpa; Pekkala, Satu (MDPI, 2021)Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat ...
Blocking Activin Receptor Ligands Is Not Sufficient to Rescue Cancer-Associated Gut Microbiota : A Role for Gut Microbial Flagellin in Colorectal Cancer and Cachexia? Pekkala, Satu; Keskitalo, Anniina; Kettunen, Emilia; Lensu, Sanna; Nykänen, Noora; Kuopio, Teijo; Ritvos, Olli; Hentilä, Jaakko; Nissinen, Tuuli A.; Hulmi, Juha J. (MDPI AG, 2019)Colorectal cancer (CRC) and cachexia are associated with the gut microbiota and microbial surface molecules. We characterized the CRC-associated microbiota and investigated whether cachexia affects the microbiota composition. ...
Irradiation of the head reduces adult hippocampal neurogenesis and impairs spatial memory, but leaves overall health intact in rats Lensu, Sanna; Waselius, Tomi; Mäkinen, Elina; Kettunen, Heikki; Virtanen, Ari; Tiirola, Marja; Penttonen, Markku; Pekkala, Satu; Nokia, Miriam S. (Wiley-Blackwell, 2021)Treatment of brain cancer, glioma, can cause cognitive impairment as a side‐effect, possibly because it disrupts the integrity of the hippocampus, a structure vital for normal memory. Radiotherapy is commonly used to treat ...
Hannonen, Riitta; Aunola, Kaisa; Eklund, Kenneth; Ahonen, Timo (MDPI, 2019)The purpose of this study is to examine differences in parenting styles between mothers of children with type 1 diabetes and mothers of healthy children and to explore relationships between parenting styles and glycemic ...
Associations of physical activity, sedentary time, and diet quality with biomarkers of inflammation in children Haapala, Eero A.; Väistö, Juuso; Ihalainen, Johanna K.; Tomaselli González, Claudia; Leppänen, Marja H.; Veijalainen, Aapo; Sallinen, Taisa; Eloranta, Aino-Maija; Ekelund, Ulf; Schwab, Ursula; Brage, Soren; Atalay, Mustafa; Lakka, Timo A. (Taylor & Francis, 2022)We investigated the associations of physical activity (PA), sedentary time (ST), and diet quality with biomarkers of inflammation in 390 children (192 girls, 198 boys) aged 6-8 years. PA energy expenditure (PAEE), light ...