Editors' ChoiceMultiple Sclerosis

Going with your gut in multiple sclerosis

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Science Translational Medicine  04 Oct 2017:
Vol. 9, Issue 410, eaap8164
DOI: 10.1126/scitranslmed.aap8164


The gut microbiome plays a key role in the pathogenesis of multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated central nervous system demyelinating disease with devastating consequences, poor etiology, and few treatments. However, growing evidence suggests that environmental factors may trigger disease onset. The human intestine, home to our diverse gut microbiome, represents one source of environmental trigger signals believed to contribute to neurological diseases. Cekanaviviute et al. studied the gut bacterial composition in MS patients and healthy controls to understand the role of the gut microbiome on MS.

Inspired by earlier studies hinting at roles for microbial imbalance in the pathogenesis of MS, the team recruited over 70 MS patients and healthy controls for gene sequencing analyses of intestinal bacteria. Global shifts in microbial community structure were not observed. However, two bacterial taxa, Akkermansia muciniphila and Acinetobacter calcoaceticus, were more abundant in the MS patients’ microbiomes compared with healthy controls. When naïve human immune cells (peripheral blood mononuclear cells) were exposed to these bacteria in the form of heat-inactivated, sonicated extracts, they induced proinflammatory T lymphocyte responses consistent with autoimmune inflammation in MS. In addition, authors found that MS patient microbiomes had a decreased amount of Parabacteroides distasonis, a taxon associated with favorable, anti-inflammatory responses. Last, they colonized antibiotic-treated, germ-free mice with microbiota from MS patients or healthy controls before the induction of experimental autoimmune encephalomyelitis, a mouse model of MS. Mice receiving MS patients’ microbiota developed a more severe disease phenotype compared with animals receiving microbiota from healthy controls and showed a proinflammatory T lymphocyte profile. Despite differences between human and mouse microbiota, these findings identify specific gut bacteria in humans that create a sustained proinflammatory environment amenable to precipitating the disease in an animal model of MS. Although the signaling factors mediating these effects and their consequences on myelination remain to be elucidated, the results of this study provide clues as to how the gut microbiome can modulate proinflammatory responses to affect MS.

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