Infection and alterations in the intestinal microbiota are often associated with multiple sclerosis (MS). In the Proceedings of the National Academy of Sciences USA, Ito and colleagues generate a humanized mouse with transgenic expression of a TCR from a patient with MS to assess the influence of age and the gut microbiota on experimental autoimmune encephalitis (EAE), the mouse counterpart of MS. A subset of these transgenic mice spontaneously develop EAE in an age-dependent way, with young adult mice being the most vulnerable, whereas disease fails to manifest in mice over 18 weeks of age. The microbiota is also relevant, as mice treated with antibiotics are protected and alterations in the frequency of particular gut bacteria species (dysbiosis) leads to a greater abundance of complement C3 in the periphery and precedes disease onset. The concentration of feces-associated immunoglobulin M (a proxy of gut inflammation) is also a useful predictor of EAE development.

Proc. Natl. Acad. Sci. USA (16 October 2017) 10.1073/pnas.1615715114