Optimizing bacteriotherapy to prevent or treat food allergy

Abstract

Abstract Depletion of protective gut microbes strongly correlates with the increasing prevalence of non-communicable diseases, including food allergies. In previous work we transferred feces from healthy or cow’s milk allergic (CMA) infants to germ free mice and showed that healthy infants harbor intestinal bacteria that are causally protective against food allergy in this model. Monocolonization with a single bacterial species, Anaerostipes caccae, was sufficient to mimic the protective effect of the healthy microbiota. These studies have provided the conceptual basis for the use of bacteriotherapy to prevent food allergy. We are taking a synbiotic approach in which we co-deliver a new sub-strain (A. caccae_lahuc), isolated from the feces of infants in our study, with prebiotic substrates that enhance the ability of A. caccae_lahuc to grow in mice with a replete microbiota and produce butyrate, a short-chain fatty acid with immunoregulatory properties. In vitro studies of A. caccae_lahuc cultured with fecal bacteria from a CMA infant identified potato starch or the combination of lactate and acetate, the intermediate products of fiber breakdown, as prebiotics which maximize butyrate output. We are optimizing delivery of these prebiotics with A. caccae_lahuc to determine whether they stimulate butyrate production in vivo. We found that A. caccae_lahuc bacteriotherapy without prebiotics leads to its stable colonization in mice already colonized with the CMA microbiota without measurable increases in fecal or cecal butyrate. By decoupling growth from butyrate release, we are obtaining mechanistic insights into the components necessary to optimize a synbiotic formulation efficacious for the prevention or treatment of food allergy.