title: Fecal microbiota composition differs between children with β-cell autoimmunity and those without.
abstract: 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.
authors.affiliation: Department of Medical Microbiology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Marcus C
authors.initials: MC
authors.lastname: de Goffau
authors.forename: Kristiina
authors.initials: K
authors.lastname: Luopajärvi
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Terhi
authors.initials: T
authors.lastname: Ruohtula
authors.forename: Taina
authors.initials: T
authors.lastname: Härkönen
authors.forename: Laura
authors.initials: L
authors.lastname: Orivuori
authors.forename: Saara
authors.initials: S
authors.lastname: Hakala
authors.forename: Gjalt W
authors.initials: GW
authors.lastname: Welling
authors.forename: Hermie J
authors.initials: HJ
authors.lastname: Harmsen
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000235:genetics / Q000502:physiology*; D001419:Bacteria / Q000145:classification* / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005243:Feces / Q000382:microbiology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D014644:Genetic Variation; D005838:Genotype; D059866:HLA-DQ beta-Chains / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology*; D008297:Male
chemical_list: D001323:Autoantibodies; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen