Low incidence of spontaneous type 1 diabetes in non-obese diabetic mice raised on gluten-free diets is associated with changes in the intestinal microbiome

• Published in: PloS one 2013-11, Vol.8 (11), p.e78687
• Main Authors: Marietta, Eric V, Gomez, Andres M, Yeoman, Carl, Tilahun, Ashenafi Y, Clark, Chad R, Luckey, David H, Murray, Joseph A, White, Bryan A, Kudva, Yogish C, Rajagopalan, Govindarajan
• Format: Article
• Language: English
• Subjects: Albumen; Animals; Antigens; Arthritis; Autoantibodies - blood; Autoimmune diseases; Blood glucose; Casein; Celiac disease; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - prevention & control; Diet; Diet, Gluten-Free; Dietary Proteins - adverse effects; Digestive system; Digestive tract; Endocrinology; Feasibility studies; Fecal microflora; Feces - microbiology; Female; Gastroenterology; Gastrointestinal tract; Gluten; Gluten-free diet; Glutens - adverse effects; Hepatology; Humans; Hyperglycemia; Immunoglobulin G - blood; Immunology; Incidence; Insulin; Insulin - immunology; Intestinal microflora; Intestine; Intestines - microbiology; Male; Metabolism; Mice; Mice, Inbred NOD; Microbiomes; Microbiota; Microbiota (Symbiotic organisms); Nutrition research; Obesity; rRNA 16S; Small intestine; Species; T-Lymphocytes, Regulatory - immunology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078687

Human and animal studies strongly suggest that dietary gluten could play a causal role in the etiopathogenesis of type 1 diabetes (T1D). However, the mechanisms have not been elucidated. Recent reports indicate that the intestinal microbiome has a major influence on the incidence of T1D. Since diet is known to shape the composition of the intestinal microbiome, we investigated using non-obese diabetic (NOD) mice whether changes in the intestinal microbiome could be attributed to the pro- and anti-diabetogenic effects of gluten-containing and gluten-free diets, respectively. NOD mice were raised on gluten-containing chows (GCC) or gluten-free chows (GFC). The incidence of diabetes was determined by monitoring blood glucose levels biweekly using a glucometer. Intestinal microbiome composition was analyzed by sequencing 16S rRNA amplicons derived from fecal samples. First of all, GCC-fed NOD mice had the expected high incidence of hyperglycemia whereas NOD mice fed with a GFC had significantly reduced incidence of hyperglycemia. Secondly, when the fecal microbiomes were compared, Bifidobacterium, Tannerella, and Barnesiella species were increased (p = 0.03, 0.02, and 0.02, respectively) in the microbiome of GCC mice, where as Akkermansia species was increased (p = 0.02) in the intestinal microbiomes of NOD mice fed GFC. Thirdly, both of the gluten-free chows that were evaluated, either egg white based (EW-GFC) or casein based (C-GFC), significantly reduced the incidence of hyperglycemia. Interestingly, the gut microbiome from EW-GFC mice was similar to C-GFC mice. Finally, adding back gluten to the gluten-free diet reversed its anti-diabetogenic effect, reduced Akkermansia species and increased Bifidobacterium, Tannerella, and Barnesiella suggesting that the presence of gluten is directly responsible for the pro-diabetogenic effects of diets and it determines the gut microflora. Our novel study thus suggests that dietary gluten could modulate the incidence of T1D by changing the gut microbiome.