OBJECTIVES: Previous studies found that children with siblings, farm residence, and other proxies of greater microbial contacts had lower rates of hyper-responsive immune disorders. Yet, scientific debate persists regarding whether the human immune system is educated in early life primarily as a function of pathogenic or benign microbial exposures, or both. Furthermore, pregnancy relies on women's intrinsic immunosuppressive function, yet it remained unknown how immunoregulation in pregnant women relates to early-life microbial exposures. Here, we conduct a preliminary examination of whether childhood microbial exposures prime women's pregnancy-related immunoregulatory capacity. METHODS: We administered retrospective questionnaires to estimate 55 pregnant women's early-life exposure to pathogenic (e.g., illness) and benign (e.g., pets
rural residence) microbes. Tolerogenic regulatory T-cells (Tregs) and Treg subtypes were measured by flow cytometry from peripheral blood. RESULTS: Results show that proxies for both pathogenic and benign exposures were positively associated with Treg concentrations. CONCLUSIONS: These findings offer insights that may help elucidate the relative contributions of early-life pathogenic ("hygiene hypothesis") and benign ("old friends hypothesis") microbial exposures toward the expansion of the Treg compartment. Human evolutionary history is characterized by changing microbial exposures as human residency patterns, living environments, and subsistence strategies changed. In this context, our findings suggest the possibility of less gestational pathology in human evolutionary past conditions typified by richer diversity of microbial exposure.