Researchers at The University of Texas Health Science Center at Houston (UTHealth) have found a link between gut microbiota and defects in the body’s T regulatory cell–induced autoimmune disease, which could lead to a treatment for children with a rare and often fatal disease called IPEX syndrome.

The finding, based on a preclinical study and published in The Journal of Experimental Medicine, suggests that giving a probiotic or restoring a key metabolite called inosine, could be beneficial for children with immunodysregulation– polyendocrinopathy–enteropathy syndrome with X–linked inheritance (IPEX syndrome).

T regulatory cells help suppress the immune system and prevent it from attacking the body’s own tissues. Defects to these regulatory cells can cause inflammation and lead to various types of autoimmune diseases. In the case of IPEX syndrome, mutations in a protein called transcription factor Foxp3 disrupt T regulatory cell function and cause the syndrome. This inherited autoimmune disorder is characterized by a variety of inflammatory conditions including eczema, type I diabetes and severe enteropathy (disease of the small intestine). Without a stem cell transplant from a suitable donor, IPEX syndrome patients usually die before the age of 2.

Autoimmune diseases can also be promoted by changes in the gut microbiome, which is the population of bacteria that reside within the gastrointestinal tract. Bacteria can secrete molecules (metabolites) that have large effects on the digestive and immune systems. The levels of a metabolite called inosine were reduced in mice lacking Foxp3, which showed changes in their gut microbiome around the same time that they developed autoimmune symptoms.

In particular, the mice had lower levels of the beneficial genus Lactobacillus, according to co–principal investigators Yuying Liu, PhD, MEd, associate professor of gastroenterology at McGovern Medical School, and J. Marc Rhoads, M.D., director of the Division of Gastroenterology in the Department of Pediatrics at McGovern Medical School.

The researchers also discovered that by feeding the mice with the “good” bacteria L. reuteri, they could “reset” the gut bacterial community and reduce the levels of inflammation in lung, spleen, intestine and even skin.

“Our findings suggest that the probiotic L. reuteri or the metabolite inosine could be used therapeutically to control T cell–mediated autoimmunity,” Liu said.

The study, “Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency–induced autoimmunity via adenosine A2A receptors,” was funded by the National Institutes of Health and BioGaia AB.