The Diet-Microbiome-Immune Trifecta: Understanding its Impact on Child Health
In pediatric autoimmunity the immune system malfunctions and attacks the body, resulting in debilitating chronic symptoms. There are no disease-specific therapies for children, and general immunosuppressants developed for adults can have severe side effects, including stunted growth and delayed puberty. We have only recently come to appreciate that a child’s developing immune system functions differently than an adult one. One of the major influences over the developing immune system is the gut microbiome, the millions of bacteria that naturally live in our bodies, which also develop during childhood. Increasingly, changes in the gut microbiome are associated with autoimmunity, but we do not yet fully understand how is it that bacteria in the intestines can influence disease outside of the gut.
We recently discovered a group of immune cells, a subset of B cells, that are trained in the gut and are microbiome-dependent yet are present in almost every organ outside the gut. We have shown that these cells accumulate in the inflamed joints in a mouse model of arthritis. These cells have the potential to act as microbiome ‘messengers’ outside the gut, but we understand almost nothing about them. Dysfunctional B cells are one of the main contributors to juvenile idiopathic arthritis (JIA), the pediatric version of autoimmune arthritis. We think that the reported microbiome changes in children with JIA result in dysfunctional B cells in the intestines that migrate into joints to actively participate in disease. Because these cells are trained in the gut, we will test which changes to the gut environment can manipulate these cells and restore them to a healthy function to improve JIA symptoms.
By uncovering how the gut environment affects B cells in JIA, this research may point to new ways to treat the disease, specifically in childhood. If we can better understand what triggers dysfunctional B cells in early life, we could develop better strategies to improve the quality of life of children living with pediatric autoimmunity.