Developing synbiotic bacterial therapeutics to treat food allergy

Abstract

Abstract The recent generational rise in the incidence of food allergies has been correlated to adverse changes in the commensal microbiome, particularly depletion of potentially protective bacteria. By correlating the abundance of fecal bacteria with functional data sets between healthy and food allergic human cohorts, we have identified candidate bacteria for live biotherapeutics. Ruminococcus bromii is more abundant in healthy adult twins than their allergic counterparts and is a keystone species for the initial stages of resistant starch consumption. Anaerostipes caccae is comparatively abundant in healthy infants and uses the intermediate products of starch or fiber digestion to produce butyrate. We have observed cross-feeding between R. bromii and A. caccae in vitro and are now investigating their therapeutic potential. Monocolonization of germ free mice with A. caccae mimics the protective effects of the replete healthy microbiome in a model of food allergy. Our hypothesis is that A. caccae will not provide the same protection to a microbially replete host without the aid of additional factors (e.g. R. bromii). In mice colonized with the dysbiotic fecal bacteria of a cow’s milk allergic (CMA) infant, A. caccae colonizes but does not produce measurable butyrate, even when supplemented with potato starch. We predict that treating CMA-colonized mice with the combination therapy of potato starch, R. bromii, and A. caccae will increase luminal butyrate and influence the local gut immune environment. Our synbiotic strategy of combining protective bacteria with their preferred substrate(s) will address the current limitations of live biotherapeutics and provide insight into the microbiome/immune interactions relevant to food allergy.