Exploring the differences in intestinal dysbiosis induced by CNS inflammatory demyelination and diabetes in non-obese diabetic mice

Abstract

Intestinal dysbiosis is being evaluated as an influencing factor in human diseases. Our laboratory works on the general hypothesis that the association is bidirectional and that disease induction affects the composition of the microbiota. Non-obese diabetic (NOD) mice develop spontaneous diabetes unless active experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis, is induced. It was proposed that the complete Freund’s adjuvant used for active induction of EAE protect against diabetes. Interestingly, although oral antibiotics treatment reduces EAE severity in SJL and C57BL/6 mice, others showed that the same treatment exacerbates diabetes in adult NOD mice. We questioned whether two different diseases affecting one animal strain, the NOD mice, affected the microbiota composition differently. We hypothesized that the gut microbiota differs between the acute inflammatory and chronic progressive stages that characterize the NOD EAE model. Further, we proposed differences in the microbiota/disease axis in EAE and diabetes. We observed significant changes in the microbiota of NOD mice that developed a severe secondary form of EAE when compared with healthy control mice. The genera Coprococcus, Ruminococcus, and Akkermansia were found elevated in EAE mice while undetermined members of the families Lactobacillaceae and Christensenellaceae were significantly reduced. Furthermore, we compared the EAE and diabetes microbiome and evaluated the effects of transplantation stool samples obtained from EAE, diabetes and control mice on diabetes progression. Our findings support the hypothesis that there are reciprocal effects between disease induction and the modification of the microbiome.