Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models

The gut microbiota regulates T cell functions throughout the body. We
hypothesized that intestinal bacteria impact the pathogenesis of multiple
sclerosis (MS), an autoimmune disorder of the central nervous system, and
thus analyzed the microbiomes of 71 MS patients not undergoing treatment
and 71 healthy controls. Although no major shifts in microbial community
structure were found, we identified specific bacterial taxa that were
significantly associated with MS. Akkermansia muciniphila and
Acinetobacter calcoaceticus, both increased in MS patients, induced
pro-inflammatory responses in human PBMCs and in mono-colonized mice. In
contrast, Parabacteroides distasonis, which was reduced in MS patients,
stimulated anti-inflammatory interleukin-10 (IL-10)-expressing human
CD4+CD25+ T cells, and IL-10+FoxP3+ regulatory T cells (Tregs) in mice.
Finally, microbiota transplants from MS patients into germ-free mice
resulted in more severe symptoms of experimental autoimmune
encephalomyelitis (EAE) and reduced proportions of IL-10+ Tregs compared
to mice “humanized” with microbiota from healthy controls. This study
identifies specific human gut bacteria that regulate adaptive autoimmune
responses, suggesting therapeutic targeting of the microbiota as a novel
treatment for MS.