The Microbiome and Food Allergies

The Microbiome and Food Allergies Presented by Wayne Shreffler, MD PhD June 2020 Today’s Presenter Wayne Shreffler, MD PhD Chief, Pediatric Allergy & Immunology Director, Food Allergy Center Principal Investigator, Center for Immunology & Inflammatory Diseases Massachusetts General Hospital 2 Disclosures § Aimmune Therapeutics – Scientific Advisory Board § FARE – Medical Advisory Board § Bulmann Laboratories AG – Consulting § Sanofi USA – Consulting § Vedanta Biosciences – Research support § NIAID – Research support § Food Allergy Science Initiative / Broad Institute – Research support § Massachusetts General Hospital -- Employer Disclosures Overview § Food allergy 101 • Epidemiology, hygiene and tolerance § Cohort studies indirectly suggesting a role for the microbiome § Building the case for the importance of the microbiome • Association, Functional, Intervention (in progress) § Why it matters and what the future may bring • ‘Sutton’s Law’, Prevention, Secondary Prevention and Treatment § Questions 5 H.A. Sampson / Allergology International 65 (2016) 363e369 365 Food allergy 101:Fig. 1. The percentage Epidemiology of children 0e17 years of age in the United States with a reported allergic condition in the past 12 months; 1997e2011. From Jackson KD et al. National Child Health Services Data Brief #121; May 2013. H.A. Sampson / Allergology International 65 (2016) 363e369 365 Fig. 1. The percentage of children 0e17 years of age in the United States with a reported allergic condition in the past 12Fig. months; 2. Food-induced 1997e2011. From hospital Jackson anaphylaxis KD et al. admissionsNational Child in Australia by age group from 1994 to 2005. From WK Liew et al. J Allergy Clin Immunol 2009; 123:434e42. Health Services Data Brief #121;Jackson May 2013. KD et al. National Child Health Services Data Brief #121; May 2013 Liew WK et al. J Allergy Clin Immunol 2009; 123:434e42 IgE in the serum and the likelihood that a patient would react to a food challenges, whereas today oral food challenges are the specific food.28,29 Since then, numerous studies in different patient accepted “gold standard”27,39 and efforts have been made to stan- populations have been undertaken in an attempt to refine the dardize the procedure worldwide.15 diagnostic accuracy of quantitative serum food-specific IgE mea- For decades allergists and clinicians have been aware that many surements.30,31 More recently, the advent of quantitative IgE mea- young infants “outgrow” their food allergies, especially to foods Sampson HA. Allergol Int. 2016 Oct;65(4):363–9. surements to major allergenic proteins within certain foods, e.g. Ara such as milk, egg, soy and wheat, whereas allergies to other foods, h 2 in peanut32,33 and Cor a 9 and 14 in hazelnut,34,35 has further e.g. peanuts, tree nuts and seafood, are more likely to persist improved the diagnostic accuracy of in vitro testing. In the mid- throughout life. However, it was not until6 the late 1990's when 1970's, May and Bock reported that prick skin test wheal diameters investigators began mapping allergenic (IgE-binding) epitopes on less than 3 mm greater than the negative control were unlikely to food proteins that an immunologic mechanism underlying this indicate symptomatic IgE-mediated food allergy and that OFCs phenomenon became more apparent. These studies showed that were necessary in patients with larger wheal diameters in order to children who outgrew their egg or milk allergy, i.e. about 80% of this establish symptomatic food allergy.14,36 However, in 2000, Sporik population, produced IgE antibodies primarily to conformational and colleagues reported that analogous to results with food- (3-dimensional) epitopes whereas those with persistent (lifelong) specific IgE values, the larger the prick skin test wheal diameter, allergy also generated significant quantities of IgE antibodies to the greater the likelihood that a patient would experience allergic sequential (linear) epitopes,40,41 suggesting different phenotypes of symptoms to a food and suggested wheal diameter cut-off values IgE-mediated food allergy in children. In contrast, most children that were highly predictive of positive OFCs.37 However, given the with peanut allergy, who typically do not outgrow their peanut variability in skin test extracts, methods and interpretation, and the allergy, i.e. 80%e85%, make large quantities of IgE antibodies to selected high-risk populations used in Sporik's and subsequent sequential epitopes. In addition it was shown more recently that Fig. 2. Food-induced hospital anaphylaxis admissions in Australia by age group from 1994 to 2005. From WKstudies, Liew et the al. J generalizability Allergy Clin Immunol of 2009; these 123:434 valuese42. have to be interpreted the greater a patient's IgE-binding diversity to allergenic epitopes with caution.38 Three decades ago few allergists performed oral on peanut proteins, i.e. the more different allergenic epitopes IgE in the serum and the likelihood that a patient would react to a food challenges, whereas today oral food challenges are the specific food.28,29 Since then, numerous studies in different patient accepted “gold standard”27,39 and efforts have been made to stan- populations have been undertaken in an attempt to refine the dardize the procedure worldwide.15 diagnostic accuracy of quantitative serum food-specific IgE mea- For decades allergists and clinicians have been aware that many surements.30,31 More recently, the advent of quantitative IgE mea- young infants “outgrow” their food allergies, especially to foods surements to major allergenic proteins within certain foods, e.g. Ara such as milk, egg, soy and wheat, whereas allergies to other foods, h 2 in peanut32,33 and Cor a 9 and 14 in hazelnut,34,35 has further e.g. peanuts, tree nuts and seafood, are more likely to persist improved the diagnostic accuracy of in vitro testing. In the mid- throughout life. However, it was not until the late 1990's when 1970's, May and Bock reported that prick skin test wheal diameters investigators began mapping allergenic (IgE-binding) epitopes on less than 3 mm greater than the negative control were unlikely to food proteins that an immunologic mechanism underlying this indicate symptomatic IgE-mediated food allergy and that OFCs phenomenon became more apparent. These studies showed that were necessary in patients with larger wheal diameters in order to children who outgrew their egg or milk allergy, i.e. about 80% of this establish symptomatic food allergy.14,36 However, in 2000, Sporik population, produced IgE antibodies primarily to conformational and colleagues reported that analogous to results with food- (3-dimensional) epitopes whereas those with persistent (lifelong) specific IgE values, the larger the prick skin test wheal diameter, allergy also generated significant quantities of IgE antibodies to the greater the likelihood that a patient would experience allergic sequential (linear) epitopes,40,41 suggesting different phenotypes of symptoms to a food and suggested wheal diameter cut-off values IgE-mediated food allergy in children. In contrast, most children that were highly predictive of positive OFCs.37 However, given the with peanut allergy, who typically do not outgrow their peanut variability in skin test extracts, methods and interpretation, and the allergy, i.e. 80%e85%, make large quantities of IgE antibodies to selected high-risk populations used in Sporik's and subsequent sequential epitopes. In addition it was shown more recently that studies, the generalizability of these values have to be interpreted the greater a patient's IgE-binding diversity to allergenic epitopes with caution.38 Three decades ago few allergists performed oral on peanut proteins, i.e. the more different allergenic epitopes Food allergy 101: Epidemiology FIGURE 3 Comparing rates of parent-reported versus convincing versus physician-confirmed FAs. Lieberman J, et al.Ann Asthma All Immunol; 2018121(5):S13. Gupta RS, et al. Pediatrics. 2018 Dec;142(6):e20181235. ’ cohort,20 and higher than Sicherer for FA diagnosis, such methods issue resulting in relatively high 7 et al s national estimate of 1.4% were not employed in the current rates of severe allergic reactions and in 2008. Although our data suggest study because of their expense, ED use. Previous findings of racial that the burden of childhood peanut impracticality, and concerns about differences in FA prevalence were allergy has increased over the past nonparticipation20 bias. As in past also supported here with elevated decade, the authors of a recent study work to strengthen the rigor of rates identified among non-Hispanic demonstrated that introducing our parent-reported questionnaire, African American children. Overall, peanut-containing foods alongside stringent criteria were established these findings provide critical typical complementary foods between in collaboration with an expert panel epidemiologic information that 4 and 11 months can achieve relative to exclude FAs where corresponding improves understanding of the public – reductions13 in peanut allergy risk of symptom report was not consistent health impact of childhood FA. up to 80% among high-risk infants. with immunoglobulin E mediated ACKNOWLEDGMENTS – Consequently, the National Institute FA. Nevertheless, by relying “ of Allergy and Infectious Diseases exclusively on parent-report and sponsored 2017 Addendum not directly observing symptoms ” We thank Michael Dennis, PhD, and Guidelines for the Prevention of immediately after allergenic food Nada Ganesh,

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