The chicken or the egg dilemma: intestinal dysbiosis in multiple sclerosis

Abstract

Recent findings suggest that the intestinal microbiota of patients suffering from relapsing remitting multiple sclerosis (MS) shows changes on the relative abundances of archaeal and bacterial genera. Although the richness and overall structure of the microbiota may be similar compared to the intestinal microbiota of healthy controls, elevated and reduced frequencies suggest a dysbiotic microbiota in MS. Over the past decade experimental evidence obtained in murine models of the disease highlighted the important relevance of the microbiota in the regulation of the immune system and in the severity of the disease. More recent findings on peripheral immune cells derived from human MS patients support the initial observations that changes in the microbiota may affect immunological pathways that could exacerbate disease. However, important questions remain to be answered. For instance, it is unclear whether dysbiosis precedes disease or, if in the contrary, an autoimmune disease such as MS can lead to gut dysbiosis. In this brief discussion, we speculate about this later possibility based on findings observed in murine models of disease. Further human studies are needed to answer the dilemma and determine specific immunomodulatory pathways that could have an impact on the therapeutic approaches to treat MS.

Keywords: Microbiota; dysbiosis; intestine; multiple sclerosis (MS).

Figure 1

The bidirectional nature of the gut/disease axis in the context of MS. To date, the studies performed using samples obtained from MS patients and healthy individuals suggest that relative abundances of specific gut microbes are significantly altered (Table 1). Experimental evidence suggests that changes in the microbiota might affect immune, endocrine and neuronal function (a). However, it is not known whether the intestinal disruption precedes the onset of disease or the changes occur once the immunological dysfunction that results in disease is already ongoing. Therapies that target the immune system and modulate the function of key immune cells (b) could affect their interaction with the gut microbiota (c). Disease-associated immunological responses could also affect the intestinal ecosystem, by alterations in the intestinal barrier permeability for example (d). That could also result in concomitant effects on the function of immune cells. Additionally, experimental data suggest a direct effect of the microbiota on the endocrine and the neuronal system. On the other hand, changes in mood, stress, depression and other behavioral factors that occur in MS could ultimately affect the composition of the microbiota (e). MS, multiple sclerosis; IMS, immunomodulators.