Mixed species live biotherapeutic product improves immunological tolerance in food allergy

Abstract

Abstract The human gut microbiota is central to early-life immune system education, including the establishment of immune tolerance, and thus represents an important target for the development of preventative interventions against food allergy (FA). The composition of the gut microbiota, and specific bacterial members within the microbiota, have been shown to impact allergic disease development in animal models by limiting basophil hematopoiesis, influencing macrophage polarization, and enhancing regulatory T cell activity. With a growing body of evidence showing the gut microbiota is an important environmental factor contributing to FA development comes an opportunity to translate this knowledge into novel approaches for treating and preventing FA. Using a proprietary human gut microbiota consortium, we have developed a mixed species live biotherapeutic product (LBP) to alleviate FA development and severity. We show that this LBP can directly interact with human immune cell populations modulating immune signaling pathways including TGF-beta, FFARs, chemotaxis, and NFkB inhibition. We also demonstrate that supplementation with this LBP can reduce OVA induced oral anaphylactic severity in mice with humanized gut microbiota. This protective effect may be attributed to increased fecal antigen-specific IgA levels and enhanced intestinal TGFb levels. These data describe immunological mechanism of a mixed species LBP that is protective in mouse FA model.