As opposed to IgE mediated food allergy (IFA) which can cause fatal outcomes, non-IgE mediated FA (NFA)
was initially thought to be a benign condition mediated by cellular immune responses, primarily affecting the GI mucosa.
NFA children were thought to recover well upon avoidance of offending food. Although pathogenesis of NFA is still not
well understood, recent studies indicate widely variable clinical manifestations of NFA. In parallel to our better
appreciation of clinical features of NFA, complex regulatory mechanisms of gut immune homeostasis have become
known with progress in our understanding of the gut mucosal immune system. In addition, a role of gut commensal flora
on the gut immune system has also become better understood along with the effects of dietary components. Subtle
changes in interactions between environmental factors (microbiota, dietary components, etc.) and the gut immune
responses can affect gut immune homeostasis, which can result in undesired adverse reactions to food proteins (FPs). This
review discusses recent progress in our understanding of the regulatory mechanisms of gut immune homeostasis and
recently revealed widely variable clinical presentations of NFA with respect to it pathogenesis.
Keywords: Food protein induced enterocolitis syndrome (FPIES), IgE mediated food allergy (IFA), non-IgE mediated food
allergy (NFA), gut mucosal immune system, pediatric gastroenterology, GI disorders, Cytokines, T Cell Populations, Microbiota, dietary components.
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