Clinical Assistant Professor University of Illinois College of Medicine, Peoria Peoria, Illinois, United States
Introduction/Rationale: Type 1 diabetes is due to aberrations in the immune system with a possible involvement of the intestinal microbiota. We have previously demonstrated that treatment of prediabetic female NOD mice with the histone deacetylase inhibitor Trichostatin A (TSA) prevented the progression of autoimmune diabetes irreversibly. This was accompanied by the restoration of self-tolerance in CD4+ T cells and selected changes in gene expression in the innate and adaptive immune systems. However, it is unknown whether the histone modifier could also perturb the intestinal microbiota to bestow protection against type 1 diabetes.
Methods: Prediabetic female NOD mice were treated with TSA, and changes in the intestinal microbiota were assessed by pyrosequencing of the fecal 16S rRNA. The PCR of bacterial DNA validated the levels of prominent bacterial groups studied earlier.
Results: Treatment with TSA afforded protection against diabetes without altering the gross representation of the major bacterial phyla, Bacteroides, Firmicutes, and Verrucomicrobia, as assessed by pyrosequencing of the fecal DNA. Interestingly, PCR analysis showed a positive link between drug-induced diabetes protection and abundance of Lachnospiraceae, along with a marginal decrease in Segmented Filamentous Bacteria in the gut. Other prominent bacterial groups previously implicated in diabetes were not impacted by the drug treatment.
Conclusion: The current study demonstrated a unique correlation between the abundance of certain Firmicutes members and protection against type 1 diabetes. Although previous studies suggested roles for numerous gut microbes in diabetes, they have rarely been correlated with experimentally induced robust protection as observed with TSA treatment. These data highlight the complex interactions among the evolving epigenetic landscape, the immune system, and the gut microbiome in preventing autoimmune diabetes.
