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.
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.
Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America ; Department of Dermatology, Mayo Clinic, Rochester, Minnesota, United States of America ; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States of America.
Eric V
EV
Marietta
Andres M
AM
Gomez
Carl
C
Yeoman
Ashenafi Y
AY
Tilahun
Chad R
CR
Clark
David H
DH
Luckey
Joseph A
JA
Murray
Bryan A
BA
White
Yogish C
YC
Kudva
Govindarajan
G
Rajagopalan
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D055050:Diet, Gluten-Free; D004044:Dietary Proteins / Q000009:adverse effects; D005243:Feces / Q000382:microbiology; D005260:Female; D005983:Glutens / Q000009:adverse effects*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D015994:Incidence; D007328:Insulin / Q000276:immunology; D007422:Intestines / Q000382:microbiology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D064307:Microbiota; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D001323:Autoantibodies; D004044:Dietary Proteins; D007074:Immunoglobulin G; D007328:Insulin; D005983:Glutens