Fecal Microbiota Composition Differs Between Children With β-Cell Autoimmunity and Those Without

• Published in: Diabetes (New York, N.Y.) Vol. 62; no. 4; pp. 1238 - 1244
• Main Authors: de Goffau, Marcus C., Luopajärvi, Kristiina, Knip, Mikael, Ilonen, Jorma, Ruohtula, Terhi, Härkönen, Taina, Orivuori, Laura, Hakala, Saara, Welling, Gjalt W., Harmsen, Hermie J., Vaarala, Outi
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.04.2013
• Subjects: Adolescent; Autoantibodies - genetics; Autoantibodies - physiology; Autoimmunity; Bacteria - classification; Bacteria - isolation & purification; Biological and medical sciences; Child; Child, Preschool; Development and progression; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feces - microbiology; Female; Gene Expression Regulation - immunology; Genetic Variation; Genotype; HLA-DQ beta-Chains - genetics; HLA-DQ beta-Chains - metabolism; Humans; Insulin-Secreting Cells - immunology; Male; Medical sciences; Original Research; Pancreatic beta cells; Physiological aspects; Type 1 diabetes; Netherlands; Finland; Endocrinopathy; Human; Autoimmunity; Diabetes mellitus; Langerhans islet; Microflora; β Cell; Child; Endocrine pancreas
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db12-0526

The role of the intestinal microbiota as a regulator of autoimmune diabetes in animal models is well-established, but data on human type 1 diabetes are tentative and based on studies including only a few study subjects. To exclude secondary effects of diabetes and HLA risk genotype on gut microbiota, we compared the intestinal microbiota composition in children with at least two diabetes-associated autoantibodies (n = 18) with autoantibody-negative children matched for age, sex, early feeding history, and HLA risk genotype using pyrosequencing. Principal component analysis indicated that a low abundance of lactate-producing and butyrate-producing species was associated with β-cell autoimmunity. In addition, a dearth of the two most dominant Bifidobacterium species, Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and an increased abundance of the Bacteroides genus were observed in the children with β-cell autoimmunity. We did not find increased fecal calprotectin or IgA as marker of inflammation in children with β-cell autoimmunity. Functional studies related to the observed alterations in the gut microbiome are warranted because the low abundance of bifidobacteria and butyrate-producing species could adversely affect the intestinal epithelial barrier function and inflammation, whereas the apparent importance of the Bacteroides genus in development of type 1 diabetes is insufficiently understood.