The Intestinal Barrier in Multiple Sclerosis: Implications for Pathophysiology and Therapeutics

Carlos R. Camara-Lemarroy; Luanne Metz; Jonathan B. Meddings; Keith A. Sharkey; V. Wee Yong


Brain. 2018;141(7):1900-1916. 

In This Article

Concluding Remarks

The recent interest in the role of the gut microbiota in multiple sclerosis has not been accompanied by a similar interest in the intestinal barrier. The intestinal barrier is the physical and functional zone of interaction between the luminal microbiome and the organism, and it is also responsible for modulating multiple biochemical processes and immune modulation of the mucosa. It appears that besides dysbiotic changes in the gut microbiome, the intestinal barrier function is also altered both in EAE models and in patients with multiple sclerosis, but the precise consequences of this alteration are unclear. Evidence of CNS demyelination in gastrointestinal disorders where there is barrier breakdown and basic studies showing how the intestinal barrier homeostasis can directly influence microglia and neuroinflammation provide some insights. Furthermore, most disease-modifying therapies appear to also impact on the intestinal barrier and the gut microbiome. To advance the understanding of this complex interaction, future studies will have to take into consideration the microbiome, the intestinal barrier and the downstream neuroimmunological changes to accommodate for them in a single integrative model. Both the precise mechanisms involved in the breakdown of the intestinal barrier, and the value, if any, of therapeutic modulation of the intestinal barrier in multiple sclerosis, also require further study.