The microbiota of the intestine shapes both local and systemic immune compartments. In Cell Host and Microbe, McCoy and colleagues reveal that bacterial colonization of the neonatal intestine also influences long-term production of immunoglobulin E (IgE). Germ-free mice develop progressively increasing serum IgE titers, whereas other immunoglobulin isotypes are unaffected. That increase in IgE is dependent on the presence of both CD4+ T cells and interleukin 4 (IL-4) but cannot be normalized by adoptive transfer of regulatory T cells (Treg cells) or treatment with IL-10. Furthermore, germ-free mice fed an antigen-free diet also develop 'hyper-IgE', which rules out the possibility of the presence of an oral allergen. Instead, the dysregulated IgE production seems to result from diminished diversity of intestinal microbes. Accordingly, exposure of germ-free mice to a diversified microbiota during a short neonatal window is sufficient to forestall switching to IgE. Therefore, diversity of the intestinal microbiota early in life also seems to set the propensity to spontaneously develop IgE and, potentially, systemic allergy.

Cell Host Microbe 14, 559–570 (2013)