Abstract
Studies in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, have shown potential links between diet components, microbiome composition, and modulation of immune responses. In this review, we reanalyze and discuss findings in an outbred marmoset EAE model in which a yogurt-based dietary supplement decreased disease frequency and severity. We show that although diet has detectable effects on the fecal microbiome, microbiome changes are more strongly associated with the EAE development. Using an ecological framework, we further show that the dominant factors influencing the gut microbiota were marmoset sibling pair and experimental time point. These findings emphasize challenges in assigning cause-and-effect relationships in studies of diet-microbiome-host interactions and differentiating the diet effects from other environmental, stochastic, and host-related factors. We advocate for animal experiments to be designed to allow causal inferences of the microbiota's role in pathology while considering the complex ecological processes that shape microbial communities.