Causal effects of the microbiota on immune-mediated diseases

The mammalian immune system has evolved in the presence of a complex community of indigenous microorganisms that constitutively colonize all barrier surfaces. This intimate relationship has resulted in the development of a vast array of reciprocal interactions between the microbiota and the host immune system, particularly in the intestine, where the density and diversity of indigenous microbes are greatest. Alterations in the gut microbiota have been correlated with almost every known immunological disease, but in most cases, it remains unclear whether these changes are a cause or effect of the disease or merely a reflection of epidemiological differences between groups. Here, we review recent efforts to demonstrate a causal role for the microbiota in health and disease, outline experimental advances that have made these studies possible, and highlight how changes in microbial composition may influence immune system function.