Figure 1.

Study design: Microbiome composition, intestinal inflammation and the development of clinical type 1 diabetes (T1D) during the follow-up. 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. Case-control pairs were 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 HBD2, calprotectin, and secretory total IgA, were performed using fecal samples. Blood samples were analyzed for the levels of ASCA IgA/IgG and circulating cytokines IFNG, IL-17, and IL-22. After the analyses, the children were followed for development of clinical T1D (median 8 years and 8 months). During the follow-up nine autoantibody-positive children were diagnosed with T1D, whereas none of the autoantibody-negative children developed T1D.