Chronic stress exposure increases diabetes incidence and alters gut microbiota in nod/shiltj mice

Abstract

Type 1 diabetes (T1D) is characterized by impaired insulin secretion and it has been recognized the contribution of psychosocial factors (including chronic stress exposure) in T1D. Gut microbiota is the group of microorganisms (commensal, symbiotic and pathogenic) that we find in our gut. It participates in multiple functions and an association between unbalanced microbiota and several diseases, including diabetes, has been reported. NOD/ShiLtJ mice are a model for autoimmune type 1 diabetes. The aim of the present work is to study the effect of chronic stress in diabetes development and to characterize the microbiota alterations in NOD/ShiLtJ mice. For this purpose, the animals were subject to chronic stress (CS) by the application of aleatory and unpredictable stressors. NOD/ShiLtJ mice exposed to CS (NOD + CS) showed an increase in diabetes incidence (Long-rank test, p<0.05) and higher glycemia levels (t test, p<0.001). Serum samples were collected and the titter for autoantibodies against insulin was measured by ELISA. NOD + CS had a lower antibody titer (t test, p<0.05). To determine microbiota alterations, fecal samples were collected and genomic DNA was extracted. 16s total bacteria, 16s Bacteriodetes and 16s Firmicutes (the most abundant components of the microbiota) were measured by qPCR using specific primers. No changes were detected in 16s total bacteria and 16s Firmicutes but a decrease in 16s Bacteroidetes was found in NOD + CS (t test p<0.05). These results show that CS has a role in type 1 diabetes development and alters gut microbiota composition, and they could suggest that the decrease in 16s bacteroidetes may participate in type 1 diabetes development.