Fecal Microbiota Composition Differs Between Children With β-Cell Autoimmunity and Those Without
- Marcus C. de Goffau1,
- Kristiina Luopajärvi2,
- Mikael Knip3,4,5,
- Jorma Ilonen6,7,
- Terhi Ruohtula2,
- Taina Härkönen3,
- Laura Orivuori2,
- Saara Hakala2,
- Gjalt W. Welling1,
- Hermie J. Harmsen1 and
- Outi Vaarala2⇑
- 1Department of Medical Microbiology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands
- 2Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland
- 3Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
- 4Folkhälsan Research Center, Helsinki, Finland
- 5Department of Pediatrics, Tampere University Hospital, Tampere, Finland
- 6Immunogenetics Laboratory, University of Turku, Turku, Finland; and the
- 7Department of Clinical Immunology, University of Eastern Finland, Kuopio, Finland.
- Corresponding author: Outi Vaarala, .
M.C.d.G. and K.L. contributed equally to this study.
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0526/-/DC1.
- Received May 2, 2012.
- Accepted November 2, 2012.
- © 2013 by the American Diabetes Association.
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