High frequency of intestinal T_H17 cells correlates with microbiota alterations and disease activity in multiple sclerosis.

Abstract

T helper 17 (T_H17) cells are key players in multiple sclerosis (MS), and studies in animal models demonstrated that effector T_H17 cells that trigger brain autoimmunity originate in the intestine. We validate in humans the crucial role of the intestinal environment in promoting T_H17 cell expansion in MS patients. We found that increased frequency of T_H17 cells correlates with high disease activity and with specific alterations of the gut mucosa-associated microbiota in MS patients. By using 16<i>S</i> ribosomal RNA sequencing, we analyzed the microbiota isolated from small intestinal tissues and found that MS patients with high disease activity and increased intestinal T_H17 cell frequency showed a higher Firmicutes/Bacteroidetes ratio, increased relative abundance of <i>Streptococcus</i>, and decreased <i>Prevotella</i> strains compared to healthy controls and MS patients with no disease activity. We demonstrated that the intestinal T_H17 cell frequency is inversely related to the relative abundance of <i>Prevotella</i> strains in the human small intestine. Our data demonstrate that brain autoimmunity is associated with specific microbiota modifications and excessive T_H17 cell expansion in the human intestine.