Gut Microbes Could Treat Autoimmune Disorder

Highlights

• Faulty T-cells lead to inflammation that results in autoimmune disorder.
• Replacing the gut microbiota and introduction of inosine found to cure autoimmune disorder IPEX syndrome.
• Gut microbes play a key role in maintaining health and could also aid in treating autoimmune disorder.

Gut microbes share a very delicate relationship with our body. It is common knowledge that these microorganisms aid in digestion and also help in crowding the gut with no space for the colonization of harmful microbes. Scientists have now found that gut microbes could play a key role in the management of autoimmune disorders.

An autoimmune disorder called the IPEX syndrome is a rare condition that affects children as young as 6 months. Scientists from The University of Texas Health Centre have found that certain defects in the T-cells in the body lead to inflammation and result in an autoimmune disease as they alter the bacteria living in the gut. The study published in the Journal of Experimental Medicine shows that replacing the bacteria or including an important metabolite called inosine could be a possible cure for IPEX syndrome.

The regulatory T-cells that are present in the body prevent the body's own T-cells from attacking the tissues in the body. However, when these regulatory T-cells become faulty, then it leads to autoimmune disease like the IPEX syndrome.

Gut Microbiome and Gastrointestinal Disorder

The gut microbiome can also result in an autoimmune disorder, according to the study by Yuying Liu and J. Marc Rhoads from The University of Texas Health Science Center. Disruptions in the Foxp3 transcription factor were found to disrupt the regulation of the T-cells which, lead to the development of IPEX syndrome.

Mice that carried a mutant version of the Foxp3 gene were found to

• Show changes in the gut microbiome
• At the same time there was development of autoimmune disorder
• The mice had lower levels of lactobacilli
• When the mice were fed with Lactobacilli reuteri, the level of inflammation was lowered

Bacteria that live in the gut of humans secrete certain metabolites. The metabolite inosine was low in people with faulty Foxp3 factor, the level of inosine was found to be normal when Lactobacilli reuteri was introduced into the gut. Inosine binds to adenosine A2A receptors that prevent the synthesis of Th1 and Th2 cells. These inflammatory T-cell types were found to be elevated in mice that were deficient in Foxp3 but on introduction of Lactobacilli or inosine, the inflammation was reduced while the lifespan of the mice increased.

Yuying Liu added that "Our findings suggest that probiotic L. reuteri, inosine, or other A2A receptor agonists could be used therapeutically to control T cell-mediated autoimmunity."

IPEX Syndrome

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a group of autoimmune disordersthat affect many parts of the body. Males are more often affected than females but it is fatal during early childhood.

In the IPEX syndrome, the cells in the intestine are damaged resulting in a condition called enteropathy. This can lead to severe diarrhea which prevents the child from gaining weight, leading to weakness. It can also lead to an inflammation of the skin called dermatitis, with red patches all over the body. An autoimmune condition of the pancreas results in the development of type 1 diabetes.

Diet Found to Influence Autoimmune Disease via Gut Microbes

Studies conducted earlier have shown that diet can influence the type of gut microbe present in the body, which can improve autoimmune condition. When the body's defense fights against a foreign invasion, there is an increase in heat, inflammation along with redness in the area. However, in an autoimmune condition, the body's defense mechanism fights against its own tissues, which result in an inflammatory reaction that lasts for a prolonged period of time. This extended exposure to inflammation can damage the tissue.

The study by Dr. Thirumala-Devi Kanneganti from St. Jude's hospital showed that the diet consumed influences the type of bacteria that grow in our gut, which in turn influence autoimmune disorder. Mice that had a condition that was similar to chronic recurrent multifocal osteomyelitis were fed with a normal diet, they developed enlarged lymph nodes, bone erosion and hind paw inflammation within a period of 100 days.

When the mutant mice were fed with a diet that was rich in saturated fat and cholesterol, they were protected from the effects of the autoimmune condition. This study shows that gut microbes can play a beneficial role in autoimmune disorders.

Gut Bacteria Could Cause Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune disease that results in pain in the joints and inflammation. Over a period of time, it could lead to damage to the lungs and to the kidney. This autoimmune condition can occur at any stage with the reason unknown. In a previous study, it was found that people who were detected with rheumatoid arthritis showed that Prevotella copri was found in 75% of the patient's intestine.

These studies show that the type of microbes that are present in our gut could either aid us in lowering the effect of an autoimmune condition or could trigger the condition. The colonization of harmful bacteria may be avoided by enriching the gut with good bacteria.

Yogurt and probiotic products are rich in 'good bacteria', the ones that will prevent unnecessary immune reaction that form the basis of autoimmunity.

References:

1. Immune Dysregulation, Polyendocrinopathy, Enteropathy, x-Linked Syndrome - (https://ghr.nlm.nih.gov/condition/immune-dysregulation-polyendocrinopathy-enteropathy-x-linked-syndrome)
2. Diet Affects Autoinflammatory Disease Via Gut Microbes - (https://www.nih.gov/news-events/nih-research-matters/diet-affects-autoinflammatory-disease-gut-microbes)

Source: Medindia