Research Group "Neuroinflammation and Mucosal Immunology" (Gurumoorthy Krishnamoorthy)
Up to 100 trillion microbes inhabit the human intestine. They are essential for health, but the disturbance of the microbiota-host relationship has been associated with various diseases. One such disease is Multiple Sclerosis (MS), as Gurumoorthy Krishnamoorthy has now shown. Together with his Research Group “Neuroinflammation and Mucosal Immunology”, he is seeking to identify the microbes responsible for triggering MS.
MS is the most common inflammatory disease of the central nervous system. In Germany alone, around 120,000 patients are affected by this serious condition that can cause vision problems, paralysis and memory loss. There is much evidence that the disease is caused by an autoimmune reaction in which the body’s immune system attacks the myelin sheath protecting the neurons. Researchers are seeking to identify the specific genetic and environmental factors involved in the disease and how they act in concert to initiate the misdirected immune response. The results from Krishnamoorthy’s group indicate that the normal intestinal microbes present in the digestive tract may also play an important role in the development of MS.
The proof for this hypothesis was obtained by means of a specially developed transgenic mouse model for MS. When the natural intestinal flora is intact in these animals, without exposure to any external influences, inflammatory responses occur in the brain which are similar to those of MS in humans. Mice lacking microbes in their gut remain healthy. When the scientists re-introduce normal intestinal microorganisms, the animals become ill showing neurological signs similar to MS.In further experiments using the mouse model, Krishnamoorthy’s group identified another important factor: the co-operation between different cell types of the immune system. It was already known that particularly aggressive T cells attack the myelin sheath of neurons. However, the researchers showed that in order to do so, the T cells must interact with antibody-producing B cells. Without the interaction of the two cell types, the MS like disease cannot occur in these animals.
Both findings once again underscore the complexity of MS. Krishnamoorthy’s group will initially focus on identifying the culprits and the good ones among the gut microbes. There are already several possible candidates: Clostridia or Enterococci for example, are components of a healthy intestinal flora, but in people, they can activate T cells in promoting or suppressing autoimmune disease.
Although, MS is not the first disease that has been associated with the microbes in the gut, there is so far no evidence of an imbalance in the composition of the intestinal flora or the colonization of “problem microbes” in human MS patients. In collaboration with the LMU Hospital Großhadern, Krishnamoorthy is seeking to determine whether this association is also found in humans. For this reason, he intends to compare the intestinal flora of MS patients and healthy subjects.
If this hypothesis proves true, the diet of people with MS may come into the spotlight of research and provide new therapeutic targets. There is already clear evidence that MS is not just a disorder of the immune system but a complex disease that has multiple causal factors.