During the past decade, research has revealed that the vast community of micro-organisms that inhabit the gut — known as the gut microbiota — is intricately linked to human health and disease, partly as a result of its influence on systemic immune responses. Accumulating evidence demonstrates that these effects on immune function are important in neuroinflammatory diseases, such as multiple sclerosis (MS), and that modulation of the microbiome could be therapeutically beneficial in these conditions. In this Review, we examine the influence that the gut microbiota have on immune function via modulation of serotonin production in the gut and through complex interactions with components of the immune system, such as T cells and B cells. We then present evidence from studies in mice and humans that these effects of the gut microbiota on the immune system are important in the development and course of MS. We also consider how strategies for manipulating the composition of the gut microbiota could be used to influence disease-related immune dysfunction and form the basis of a new class of therapeutics. The strategies discussed include the use of probiotics, supplementation with bacterial metabolites, transplantation of faecal matter or defined microbial communities, and dietary intervention. Carefully designed studies with large human cohorts will be required to gain a full understanding of the microbiome changes involved in MS and to develop therapeutic strategies that target these changes.

• The colony of bacteria that inhabit the gut — known as the gut microbiota — varies in composition according to genetic factors and, more importantly, envorinmental influences, particularly diet.
• The composition of the gut microbiota influences the production of serotonin in the gut, which in turn influences serotonin-mediated regulation of systemic immune function.
• Gut microbiota are also involved in complex interactions with the gut and immune cells in the small intestine and the colon, thereby influencing immune responses in the periphery and the central nervous system.
• Abundant evidence indicates that the gut microbiota has a role in multiple sclerosis (MS) through its influence on immune function.
• Therapeutic strategies that target the microbiota — including dietary interventions, probiotics, short-chain fatty acids and faecal microbial transplantation — seem promising for the treatment of MS, but further work is needed to assess their effectiveness.