The microbiome requires a genetically susceptible host to induce central nervous system autoimmunity

October 29, 2020
Howard Weiner
While the risk of developing multiple sclerosis (MS) is recognized to have both genetic and environmental components, little is known about these complex interactions. The microbiome has recently been recognized as an environmental factor that contributes to MS. In Montgomery et al. (1), the authors harnessed the natural genetic diversity between B6 mice, PWD/PhJ (PWD) wild-derived mice, and a panel of 27 B6.ChrPWD consomic mice to investigate gene plus microbiome interactions. They identified chromosomes that affected disease susceptibility and also identified microbes that increased disease severity in disease-susceptible hosts. They found that while the PWD mice are resistant to experimental autoimmune encephalomyelitis (EAE), these mice surprisingly harbor a microbiota that increases central nervous system (CNS) autoimmunity when transferred into the genetically susceptible B6 mice (Fig. 1). This study advances the field by illustrating an important point: that altered microbiota alone may not be sufficient to cause MS, but rather, a perfect storm of host genetic risk plus specific microbes triggers CNS autoimmunity. Read more about recent work from the Weiner lab, published in PNAS.