Pathological changes in the gut could initiate autoimmune diabetes microbiota-specific manner

The mechanism of type 1 diabetes ( T1D ) has been investigated using the mouse strain NOD. Although it is unclear how islet-specific T cells become activated, these mice spontaneously develop autoimmune diabetes. TCR transgenic mice, BDC2.5XNOD, have been used to monitor the fate of autoimmune T cells. These mice have a large number of islet-specific TCR expressing T cells that can be easily tracked.

To better understand the onset of autoimmunity, a recent study in PNAS conducted some experiments on BDC2.5XNOD mice. By measuring the FITC – dextran level in the blood following oral application, they first demonstrated that the NOD background displayed increased gut wall barrier permeability( though they did not perform the same test for BDC2.5XNOD mice ).

It’s interesting to note that BDC2.5XNOD mice don’t spontaneously develop autoimmune diabetes. However, low-dose dextran-sulfate sodium( DSS ) oral administration activates T cells and causes diabetes.

 

Diabetes, however, does not appear in BDC2.5XNOD mice who have received DSS-modified microbiota or if they have been depleted of endogenous microbes.

In conclusion, this study demonstrated that in BDC2.5XNOD mice, autoimmune diabetes is initiated by both gut inflammation and the microbiota. The most likely scenario is that DSS-introduced changes enable endogenous microbiota to activate islet-specific T cells using cross – reactive antigens. DSS alters the microbiota and gut wall permeability. The authors have seen both of these phenomena. They come to the conclusion that” restoring a healthy gut barrier through microbiota and diet modification in diabetes-prone individuals could ultimately reduce intestinal activation of islet – reactive T cells and prevent T1D occurrence.”

Others even suggested using antibiotics to deplete endogenous microbiota in news articles and reviews for this article, but in my opinion, this is a premature suggestion because the authors did not demonstrate that depletion of the mien after diabetes has already manifested could stop it.

written by David Usharauli