Early life interventions in the intestinal environment have previously been shown to influence diabetes incidence. We therefore hypothesized that a gluten-free (GF) diet, known to decrease type 1 diabetes incidence, only during pregnancy and lactation period would protect against development of diabetes. Pregnant non-obese diabetic (NOD) mice were fed GF or standard diet, until all pups were weaned to standard diet. The early life GF environment dramatically decreased diabetes incidence and insulitis. Gut microbiota analysis by 16S rRNA gene sequencing revealed a pronounced difference between both mothers and their offspring, characterized by increased Akkermansia, Proteobacteria, and TM7 in the GF diet group. In addition, pancreatic FoxP3 regulatory T cells were increased in GF fed offspring; as were M2 macrophage gene markers and tight junction-related genes in the gut, while intestinal gene expression of proinflammatory cytokines was reduced. Increased proportion of T cells in the pancreas expressing the mucosal integrin α4β7 suggests that the mechanism involve increased trafficking of gut-primed immune cells to the pancreas. In conclusion, GF diet during fetal and early postnatal life reduces development of diabetes. The mechanism may involve a changed gut microbiota and shifts to a less proinflammatory immunological milieu in the gut and pancreas.
- Received October 18, 2013.
- Accepted March 27, 2014.
- © 2014 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.