Fecal microbiota composition differs between children with β-cell autoimmunity and those without

Diabetes. 2013 Apr;62(4):1238-44. doi: 10.2337/db12-0526. Epub 2012 Dec 28.

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.

Trial registration: ClinicalTrials.gov NCT00570102 NCT01055080.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autoantibodies / genetics
  • Autoantibodies / physiology*
  • Bacteria / classification*
  • Bacteria / isolation & purification
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • 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

Substances

  • Autoantibodies
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen

Associated data

  • ClinicalTrials.gov/NCT00570102
  • ClinicalTrials.gov/NCT01055080