Gut microbiota and fecal metabolites in sustained unresponsiveness by oral immunotherapy in school-age children with cow's milk allergy.

BACKGROUND: Oral immunotherapy (OIT) can ameliorate cow's milk allergy (CMA); however, the achievement of sustained unresponsiveness (SU) is challenging. Regarding the pathogenesis of CMA, recent studies have shown the importance of gut microbiota (Mb) and fecal water-soluble metabolites (WSMs), which prompted us to determine the change in clinical and gut environmental factors important for acquiring SU after OIT for CMA. METHODS: We conducted an ancillary cohort study of a multicenter randomized, parallel-group, delayed-start design study on 32 school-age children with IgE-mediated CMA who underwent OIT for 13 months. We defined SU as the ability to consume cow's milk exceeding the target dose in a double-blind placebo-controlled food challenge after OIT followed by a 2-week-avoidance. We longitudinally collected 175 fecal specimens and clustered the microbiome and metabolome data into 29 Mb- and 12 WSM-modules. RESULTS: During OIT, immunological factors improved in all participants. However, of the 32 participants, 4 withdrew because of adverse events, and only 7 were judged SU. Gut environmental factors shifted during OIT, but only in the beginning, and returned to the baseline at the end. Of these factors, milk- and casein-specific IgE and the Bifidobacterium-dominant module were associated with SU (milk- and casein-specific IgE; OR for 10 kUA/L increments, 0.67 and 0.66; 95%CI, 0.41-0.93 and 0.42-0.90; Bifidobacterium-dominant module; OR for 0.01 increments, 1.40; 95%CI, 1.10-2.03), and these associations were observed until the end of OIT. CONCLUSIONS: In this study, we identified the clinical and gut environmental factors associated with SU acquisition in CM-OIT.

Rush specific oral tolerance induction in school-age children with severe egg allergy: one year follow up.

BACKGROUND: At present, the only treatment for food allergy is to avoid the allergy-causing food. Some trials of specific oral tolerance induction (SOTI) have been carried out, but the rate of tolerance induction was low despite long treatment periods, at least 3 months to several years. A new type of treatment is long desired. The objectives of this study are to perform our rush SOTI for school-age patients with severe egg allergy, and to evaluate the safety and efficacy of this method for one year. METHODS: Six school-age children (7-12 years of age) with severe IgE-mediated egg allergy confirmed by double-blind, placebo-controlled food challenge (DBPCFC) underwent rush SOTI, in which patients ingested increasing doses of egg several times every day. After rush SOTI, patients ingested the maintenance dose of egg at least twice a week. RESULTS: In DBPCFC, the median threshold dose of egg white inducing allergic reactions was 0.152 g (0.012-0.360 g). All subjects acquired tolerance to more than one whole egg (60 g). It took only 12 days (9-18 days). None experienced any serious reaction. We observed a decrease in IL-10 and an increase in TGF-beta1 at 6 months and a decrease in egg-specific IgE and an increase in egg white-specific IgG4 at 12 months after rush SOTI in blood. All subjects have been able to ingest more than one whole egg ever since. CONCLUSIONS: Our rush SOTI is a safe and effective treatment for severe food allergy since only a few weeks are needed to acquire tolerance. It would replace allergen avoidance as the treatment for food allergy.