Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome

Abstract

The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.

Keywords: Bile acids; Gut-brain axis; Intestinal barrier; Microbiome; Multiple sclerosis.

Figure 1

Alterations in intestinal homeostasis described in multiple sclerosis as therapeutic targets. Altered bile acid metabolism, altered microbiota and alterations in intestinal barrier function all lead to local and systemic alterations in immune responses that could negatively impact MS pathophysiology (grey squares). Bile acid supplementation, fecal microbiota transplantation, probiotics, antibiotics and barrier protectors are all possible therapeutic interventions (blue squares). MS: Multiple sclerosis; FMT: Fecal microbiota transplantation; PC: Paneth cells; EC: Epithelial cells; TJ: Tight junctions; L: Lymphocytes.