Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD mice

Gut Microbes. 2015;6(2):101-9. doi: 10.1080/19490976.2015.1011876. Epub 2015 Feb 3.

Abstract

Gut microbiota regulated imbalances in the host's immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3(+) regulatory T cells, CD11b(+) dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24-7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all Firmicutes) promote pathogenesis.

Keywords: CD, cluster of differentiation; DC, dendritic cell; FoxP3, forkhead box; IFN, interferon; IFN-γ; MLN, mesenteric lymph node; NKT, natural killer T cell; NOD mice; PCA, principal component analysis; PCoA, principal coordinate analysis; PLN, pancreatic lymph node; Treg, regulatory T cell; Type 1 diabetes; gut microbiota; regulatory immunity; siLP, small intestinal lamina propria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / classification
  • Bacteria / genetics
  • Dendritic Cells / immunology*
  • Diabetes Mellitus, Type 1 / pathology*
  • Feces / microbiology
  • Gastrointestinal Microbiome / immunology*
  • Gastrointestinal Tract / microbiology*
  • Gastrointestinal Tract / pathology*
  • Interferon-gamma / analysis*
  • Lymphocyte Subsets / immunology*
  • Mice, Inbred NOD

Substances

  • Interferon-gamma