[en] [en] BACKGROUND AND OBJECTIVES: Peanut allergy (PA) is an IgE-mediated food allergy with variable clinical outcomes. Mild to-severe symptoms affect various organs and, often, the gastrointestinal tract. The role of intestine-derived IgE antibodies in gastrointestinal PA symptoms is poorly understood. Objective: This study aimed to examine fecal IgE responses in PA as a novel approach to patient endotyping.
METHODS: Feces and serum samples were collected from peanut-allergic and healthy children (n=26) to identify IgE and cytokines using multiplex assays. Shotgun metagenomics DNA sequencing and allergen database comparisons made it possible to identify microbial peptides with homology to known allergens.
RESULTS: Compared to controls, fecal IgE signatures showed broad diversity and increased levels for 13 allergens, including food, venom, contact, and respiratory allergens (P<.01-.0001). Overall, fecal IgE patterns were negatively correlated compared to sera IgE patterns in PA patients, with the greatest differences recorded for peanut allergens (P<.0001). For 83% of the allergens recognized by fecal IgE, we found bacterial homologs from PA patients' gut microbiome (eg, thaumatin-like protein Acinetobacter baumannii vs Act d 2, 109/124 aa identical). Compared to controls, PA patients had higher levels of fecal IgA, IL-22, and auto-IgE binding to their own fecal proteins (P<.001). Finally, levels of fecal IgE correlated with abdominal pain scores (P<.0001), suggesting a link between local IgE production and clinical outcomes.
CONCLUSIONS: Fecal IgE release from the intestinal mucosa could be an underlying mechanism of severe abdominal pain through the association between leaky gut epithelia and anticommensal TH2 responses in PA.
Disciplines :
Food science
Author, co-author :
Czolk, R; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg ; Department of Life Science and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Codreanu-Morel, F; National Unit of Immunology and Allergology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg
de Nies, L; Department of Life Science and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg ; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
BUSI, Susheel Bhanu ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Systems Ecology > Team Paul WILMES
Halder, R; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Hunewald, O; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
Boehm, T M; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg ; Department of Life Science and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Hefeng, F Q; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
De Beaufort, C; Department of Life Science and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg ; Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg ; Diabetes and Endocrine Care Clinique Pédiatrique, Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg
WILMES, Paul ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology
Ollert, M; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg ; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, Odense University Hospital, University of Southern Denmark, Odense, Denmark
KUEHN, Annette ; University of Luxembourg ; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
External co-authors :
no
Language :
English
Title :
Fecal IgE Analyses Reveal a Role for Stratifying Peanut-Allergic Patients.
Publication date :
29 July 2025
Journal title :
Journal of Investigational Allergology and Clinical Immunology
ISSN :
1018-9068
Publisher :
ESMON Publicidad S.A., Spain
Volume :
35
Issue :
4
Pages :
276 - 287
Peer reviewed :
Peer Reviewed verified by ORBi
FnR Project :
FNR11823097 - MICROH-DTU - Microbiomes In One Health, 2017 (01/09/2018-28/02/2025) - Paul Wilmes FNR16749720 - NextImmune2 - Nextimmune2: Next Generation Immunology Research, 2022 (15/10/2022-14/04/2029) - Dirk Brenner
Funding text :
Supported by the Luxembourg National Research Fund on PRIDE program grants PRIDE17/11823097/MICROH and PRIDE21/16749720/NEXTIMMUNE2.
Czolk R, Klueber J, Sørensen M, Wilmes P, Codreanu-Morel F, Skov PS, et al. IgE-Mediated Peanut Allergy: Current and Novel Predictive Biomarkers for Clinical Phenotypes Using Multi-Omics Approaches. Front Immunol. 2021;11:594350.
Botelho Alves P, Pires Pereira H, Cardoso Lopes J, Carrapatoso I, Todo-Bom A, Regateiro FS. Peeling the Peanut. Characterizing Peanut Allergy with the new Food Allergy Severity Score. J Investig Allergol Clin Immunol. 2024;34(2):125-7.
Anvari S, Miller J, Yeh CY, Davis CM. IgE-mediated food allergy. Clin Rev Allergy Immunol. 2019;57:244-60.
Frugier C, Graham F, Samaan K, Paradis L, Des Roches A, Bégin P. Potential Efficacy of High-Dose Inhaled Salbutamol for the Treatment of Abdominal Pain During Oral Food Challenge. J Allergy Clin Immunol Pract. 2021;9(8):3130-7.
Klueber J, Czolk R, Codreanu-Morel F, Montamat G, Revets D, Konstantinou M, et al. High dimensional immune profiles correlate with phenotypes of peanut allergy during food-allergic reactions. Allergy. 2023;78(4):1020-35.
Hoh RA, Joshi SA, Lee J-Y, Martin BA, Varma S, Kwok S, et al. Origins and clonal convergence of gastrointestinal IgE(+) B cells in human peanut allergy. Sci Immunol. 2020;5(45):eaay4209.
Kolmannskog S, Haneberg B. Immunoglobulin E in feces from children with allergy. Evidence of local production of IgE in the gut. Int Arch Allergy Appl Immunol. 1985;76(2):133-215.
Li H, Nowak-Wegrzyn A, Charlop-Powers Z, Shreffler W, Chehade M, Thomas S, et al. Transcytosis of IgE-antigen complexes by CD23a in human intestinal epithelial cells and its role in food allergy. Gastroenterology. 2006;131(1):47-58.
Sasai K, Furukawa S, Sugawara T, Kaneko K, Baba M, Yabuta K. IgE levels in faecal extracts of patients with food allergy. Allergy. 1992;47(6):594-8.
Abdel-Gadir A, Stephen-Victor E, Gerber GK, Noval Rivas M, Wang S, Harb H, et al. Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy. Nat Med. 2019;25(7):1164-74.
Wilmes P, Martin-Gallausiaux C, Ostaszewski M, Aho VTE, Novikova PV, Laczny CC, et al. The gut microbiome molecular complex in human health and disease. Cell Host Microbe. 2022;30(9):1201-6.
Parrish A, Boudaud M, Kuehn A, Ollert M, Desai MS. Intestinal mucus barrier: a missing piece of the puzzle in food allergy. Trends Mol Med. 2022;28(1):36-50.
Zubeldia-Varela E, Barker-Tejeda TC, Obeso D, Villaseñor A, Barber D, Pérez-Gordo M. Microbiome and Allergy: New Insights and Perspectives. J Investig Allergol Clin Immunol. 2022;32(5):327-44.
Izquierdo E, Rodriguez-Coira J, Delgado-Dolset MI, Gomez-Casado C, Barber D, Escribese MM. Epithelial Barrier: Protector and Trigger of Allergic Disorders. J Investig Allergol Clin Immunol. 2022;32(2):81-96.
Bernard H, Turner PJ, Ah-Leung S, Ruiz-Garcia M, Clare Mills EN, Adel-Patient K. Circulating Ara h 6 as a marker of peanut protein absorption in tolerant and allergic humans following ingestion of peanut-containing foods. Clin Exp Allergy. 2020;50(9):1093-102.
Steinbach EC, Smeekens JM, Roy S, Toyonaga T, Cornaby C, Perini LB, et al. Intestinal epithelial cell barrier dysfunction and elevated Angiopoietin-like 4 identified in orally susceptible peanut allergy model.Clin Exp Allergy. 2023;53(2):210-5.
Drønen EK, Namork E, Dirven H, Nygaard UC. Suspected gut barrier disruptors and development of food allergy: Adjuvant effects and early immune responses. Front Allergy. 2022;3:1029125.
Wang R, Cao S, Bashir MEH, Hesser LA, Su Y, Hong SMC, et al. Treatment of peanut allergy and colitis in mice via the intestinal release of butyrate from polymeric micelles. Nat Biomed Eng. 2023 7(1):38-55. Epub 20221222.
Carrasco Pro S, Lindestam Arlehamn CS, Dhanda SK, Carpenter C, Lindvall M, Faruqi AA, et al. Microbiota epitope similarity either dampens or enhances the immunogenicity of disease-associated antigenic epitopes. PLoS One. 2018;13(5):e0196551.
Wampach L, Heintz-Buschart A, Fritz JV, Ramiro-Garcia J, Habier J, Herold M, et al. Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential. Nat Commun. 2018;9(1):5091.
Hefeng F, Pogorelov D, Bode S, He X, Ramiro-Garcia J, Hedin F, et al. Multiomics approaches disclose very-early molecular and cellular switches during insect-venom allergen-specific immunotherapy. Research Square. Preprint. 2024. https://doi. org/10.21203/rs.3.rs-3917969/v1.
Hickl O, Heintz-Buschart A, Trautwein-Schult A, Hercog R, Bork P, Wilmes P, et al. Sample Preservation and Storage Significantly Impact Taxonomic and Functional Profiles in Metaproteomics Studies of the Human Gut Microbiome. Microorganisms. 2019;7(9):367.
Kuehn A, Scheuermann T, Hilger C, Hentges F. Important variations in parvalbumin content in common fish species: a factor possibly contributing to variable allergenicity. Int Arch Allergy Immunol. 2010;153(4):359-66.
An P, Barron-Casella EA, Strunk RC, Hamilton RG, Casella JF, DeBaun MR. Elevation of IgE in children with sickle cell disease is associated with doctor diagnosis of asthma and increased morbidity. J Allergy Clin Immunol. 2011 Jun;127(6):1440-6
Kuehn A, Codreanu-Morel F, Lehners-Weber C, Doyen V, Gomez-André SA, et al. Cross-reactivity to fish and chicken meat-a new clinical syndrome. Allergy 2016;71(12):1772-81.
Sørensen M, Kuehn A, Mills ENC, Costello CA, Ollert M, Småbrekke L, et al. Cross-reactivity in fish allergy: A double-blind, placebo-controlled food-challenge trial. J Allergy Clin Immunol. 2017;140(4):1170-2.
Velasco Rodríguez-Belvís M, Viada Bris JF, Plata Fernández C, García-Salido A, Asensio Antón J, Domínguez Ortega G, et al. Normal fecal calprotectin levels in healthy children are higher than in adults and decrease with age. Paediatr Child Health. 2020;25(5):286-92.
Roca M, Rodriguez Varela A, Carvajal E, Donat E, Cano F, Armisen A, et al. Fecal calprotectin in healthy children aged 4-16 years. Sci Rep. 2020;10(1):20565.
Heffler E, Puggioni F, Peveri S, Montagni M, Canonica GW, Melioli G. Extended IgE profile based on an allergen macroarray: a novel tool for precision medicine in allergy diagnosis. World Allergy Organ J. 2018;11(1):7.
Czolk R, Ruiz‐ Castell M, Hunewald O, Wanniang N, Le Coroller G, Hilger C, et al. Novel, computational IgE‐ clustering in a population‐ based cross‐ sectional study: Mapping the allergy burden. Clin Transl Allergy. 2023;13(9):e12292.
Narayanasamy S, Jarosz Y, Muller EE, Heintz-Buschart A, Herold M, Kaysen A, et al. IMP: a pipeline for reproducible reference-independent integrated metagenomic and metatranscriptomic analyses. Genome Biol. 2016;17(1):260.
Oksanen J SG, Blanchet F, Kindt R, Legendre P, Minchin P, O'Hara R, et al. Vegan: Community Ecology Package 2022.
Love M, Anders S, Huber W. Differential analysis of count data– the DESeq2 package. Genome Biol. 2014;15(550):10-1186.
Mallick H, Rahnavard A, McIver LJ, Ma S, Zhang Y, Nguyen LH, et al. Multivariable association discovery in population-scale meta-omics studies. PLoS Comput Biol. 2021;17(11):e1009442.
Hughes JB, Hellmann JJ, Ricketts TH, Bohannan BJ. Counting the uncountable: statistical approaches to estimating microbial diversity. Appl Environ Microbiol. 2001;67(10):4399-406.
Dang HX, Lawrence CB. Allerdictor: fast allergen prediction using text classification techniques. Bioinformatics. 2014;30(8):1120-8.
Fiers MW, Kleter GA, Nijland H, Peijnenburg AA, Nap JP, van Ham RC. Allermatch, a webtool for the prediction of potential allergenicity according to current FAO/WHO Codex alimentarius guidelines. BMC Bioinformatics. 2004;5:133.
https://www.iedb.org/. Immune Epitope database and analysis resource [cited 22.06.2021].
Li W, Cowley A, Uludag M, Gur T, McWilliam H, Squizzato S, et al. The EMBL-EBI bioinformatics web and programmatic tools framework. Nucleic Acids Res. 2015;43(W1):W580-4.
https://www.R-project.org/. Team RC. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria 2021.
Dramburg S, Hilger C, Santos AF, de Las Vecillas L, Aalberse RC, Acevedo N, et al. EAACI Molecular Allergology User's Guide 2.0. Pediatr Allergy Immunol. 2023;34 Suppl 28:e13854.
Wade-Vallance AK, Allen CDC. Intrinsic and extrinsic regulation of IgE B cell responses. Curr Opin Immunol. 2021;72:221-9.
Iweala OI, Burks AW. IgE producers in the gut expand the gut's role in food allergy. Nat Rev Gastroenterol Hepatol. 2020;17(7):384-6.
Santos AF, Du Toit G, O'Rourke C, Becares N, Couto-Francisco N, Radulovic S, et al. Biomarkers of severity and threshold of allergic reactions during oral peanut challenges. J Allergy Clin Immunol. 2020;146(2):344-55.
Aguilera-Lizarraga J, Florens MV, Viola MF, Jain P, Decraecker L, Appeltans I, et al. Local immune response to food antigens drives meal-induced abdominal pain. Nature. 2021;590(7844):151-6.
Pracht K, Wittner J, Kagerer F, Jäck HM, Schuh W. The intestine: A highly dynamic microenvironment for IgA plasma cells. Front Immunol. 2023;14:1114348.
Chen L, Ruan G, Cheng Y, Yi A, Chen D, Wei Y. The role of Th17 cells in inflammatory bowel disease and the research progress. Front Immunol. 2023;13:1055914.
Hua X, Goedert JJ, Pu A, Yu G, Shi J. Allergy associations with the adult fecal microbiota: Analysis of the American Gut Project. EBioMedicine. 2015;3:172-9.
Aitoro R, Paparo L, Amoroso A, Di Costanzo M, Cosenza L, Granata V, et al. Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy. Nutrients. 2017;9(7):672.
Feehley T, Plunkett CH, Bao R, Choi Hong SM, Culleen E, Belda-Ferre P, et al. Healthy infants harbor intestinal bacteria that protect against food allergy. Nat Med. 2019;25(3):448-53.
Kourosh A, Luna RA, Balderas M, Nance C, Anagnostou A, Devaraj S, et al. Fecal microbiome signatures are different in food-allergic children compared to siblings and healthy children. Pediatr Allergy Immunol. 2018;29(5):545-54.
Suprun M, Kearney P, Hayward C, Butler H, Getts R, Sicherer SH, et al. Predicting probability of tolerating discrete amounts of peanut protein in allergic children using epitope-specific IgE antibody profiling. Allergy. 2022;77(10):3061-9.
Reier-Nilsen T, Michelsen MM, Lødrup Carlsen KC, Carlsen KH, Mowinckel P, Nygaard UC, et al. Predicting reactivity threshold in children with anaphylaxis to peanut Clin Exp Allergy. 2018;48(4):415-23.
Santos AF, Kulis MD, Sampson HA. Bringing the Next Generation of Food Allergy Diagnostics Into the Clinic. J Allergy Clin Immunol Pract. 2022;10(1):1-9.
Chiu C-Y, Chan Y-L, Tsai M-H, Wang C-J, Chiang M-H, Chiu C-C, et al. Cross-talk between airway and gut microbiome links to IgE responses to house dust mites in childhood airway allergies. Sci Rep. 2020;10(1):13449.
Kolmannskog S, Haneberg B. Immunoglobulin E in feces from children with allergy. Evidence of local production of IgE in the gut. Int Arch Allergy Appl Immunol. 1985;76(2):133-7.
Aranda CJ, Curotto de Lafaille MA. The Secret Life of IgE-Producing Cells. Immunity. 2019;50(2):285-7.
Pier J, Liu EG, Eisenbarth S, Järvinen KM. The role of immunoglobulin A in oral tolerance and food allergy. Ann Allergy Asthma Immunol. 2021;126(5):467-8.
Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021;21(11):739-51.
Jin S, Wetzel D, Schirmer M. Deciphering mechanisms and implications of bacterial translocation in human health and disease. Curr Opin Microbiol. 2022;67:102147.
Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, et al. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science. 2018;359(6380):1156-61.
Yazici D, Cagan E, Tan G, Li M, Do E, Kucukkase OC, et al. Disrupted epithelial permeability as a predictor of severe COVID-19 development. Allergy. 2023;78(10):2644-58.
Parsons ES, Liu F, Kaushik A, Lee A, Schuetz J, Dunham D, et al. Detection of gut and mucosal peptides through TOMAHAQ in healthy individuals. Allergy. 2023;78(7):2052-5.
Sereme Y, Moïse M, Mezouar S, Oumar Guindo C, Kaba L, Grine G, et al. Multiplex Specific IgE Profiling in Neonatal Stool of Preterms Predicts IgE-Mediated Disease. Allergies. 2023;3(1):58-71.
Bourgonje AR, Andreu-Sánchez S, Vogl T, Hu S, 260 Vich Vila A, Gacesa R, et al. Phage display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures. Immunity. 2023;56(6):1393-409.e6.
Krempski JW, Dant C, Nadeau KC. The origins of allergy from a systems approach. Ann Allergy Asthma Immunol. 2020;125(5):507-16.