Effects of butyrylated high amylose maize starch (HAMSB) as an adjuvant for oral immunotherapy

BackgroundOral immunotherapy (OIT) is an important treatment option for food allergy but achieving sustained unresponsiveness (SU) via OIT is challenging. Improving SU for OIT with adjuvants is of great interest but little progress has been made so far. Gut microbiota-derived metabolites like short-chain fatty acids (SCFAs) protect against food allergy in mouse models via promoting regulatory T cells (Treg) generation. We thus aim to investigate the impacts from metabolite-based dietary supplement as an adjuvant in food allergic children receiving peanut OIT. MethodsBased on a prior phase 2 single centre open label interventional randomized controlled trial Oral Peanut Immunotherapy with Short Chain Fatty Acid Adjuvant (OPIA, ACTRN12617000914369), gut microbiota and immune profiles from food allergic children receiving peanut OIT supplemented with butyrylated high-amylose maize starch (HAMSB) or with low amylose maize starch (LAMS) were comprehensively profiled. ResultsHAMSB conferred minimal effects on gut microbiota, except transiently increasing their SCFA production like propionate and butyrate. HAMSB skewed CD4+FOXP3+ Treg towards a tolerogenic phenotype and strikingly increased anti-inflammatory CD4-FOXP3+ Treg, even after cessation of OIT and HAMSB. ConclusionsWe present the first report of the potent immune modulatory effects of dietary butyrate supplementation via HAMSB over an extended period of 1 year in food allergic children. Our findings highlight the tolerance inducing effects of HAMSB and its potential as immunotherapy adjuvant for food allergy and/or autoimmune diseases.