Study suggests gut may be involved in MS development

December 06, 2019
In a new study, researchers used an animal model to show that the protein Smad7 mobilizes immune cells in the intestines which, in turn, trigger inflammation in the central nervous system. Analyses of intestinal tissue samples taken from multiple sclerosis patients confirmed the results.

Researchers at the Department of Neurology and the Centre of Neuroimmunology at St. Josef-Hospital, university hospital of Ruhr-Universit├Ąt Bochum, initially analysed the signal protein Smad7 in intestinal immune cells in mice, or more precisely: in T-cells. The researchers compared genetically modified mice with a normal amount and those with a particularly high quantity of Smad7 in T-cells, as well as mice without any Smad7 in T-cells. They monitored if the animals developed opticospinal encephalomyelitis – a disease that mimics MS in humans.

The strongest clinical MS-like symptoms occurred in animals with an increased Smad7 level in T-cells. In their intestines, T-cells were more frequently activated, which then migrated into the central nervous system where they triggered inflammation. Moreover, the ratio of protective regulatory T-cells to pathogenic autoreactive T-cells had changed. In mice that didn't have any Smad7 protein, no clinical signs of a MS-like disease occurred.

In the next step, the researchers analysed tissue samples taken from the intestines of 27 MS patients and compared them with samples taken from 27 healthy individuals. In the patients, they identified changes similar to those in the animal model: the signal protein Smad7 occurred more frequently in intestinal mucosa samples of MS patients than in those of healthy individuals; in addition, an abnormal ratio of regulatory to pathogenic mechanisms was identified in intestinal mucosa samples in patients.

The results were published in the journal Proceedings of the National Academy of Sciences.

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