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The Role of the Microbiota in Food-induced Allergic Disorders

Applicant Noti Mario
Number 154777
Funding scheme Ambizione
Research institution Institut für Pathologie Medizinische Fakultät Universität Bern
Institution of higher education University of Berne - BE
Main discipline Immunology, Immunopathology
Start/End 01.11.2014 - 31.10.2017
Approved amount 599'156.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Experimental Microbiology

Keywords (4)

Diet; Gnotobiotic mouse models; Microbiota; Food allergy

Lay Summary (German)

Lead
Nahrungsmittelallergien, verursacht durch eine unkontrollierte Immunantwort gegenüber normalerweise harmlosen Bestandteilen der Nahrung, stellen ein stetig wachsendes globales Gesundheitsproblem dar. Eine Anzahl von Studien hat gezeigt, dass ein westlicher Lebensstil, assoziiert mit einem erhöhten Allergierisiko, einen kritischen Effekt auf die Komposition unserer Darmflora (Mikrobiota) ausübt, welche ihrerseits wichtig für die optimale Entwicklung unseres Immunsystems ist. Das Projekt untersucht die Rolle der Mikrobiota im Kontext experimentell induzierter Nahrungsmittelallergien.
Lay summary

Ziele des Forschungsprojekts bei Forschungsbeginn und die Resultate nach Abschluss des Projekts:

In dieser Studie wollen wir untersuchen, welchen Einfluss die Darmflora auf die Entwicklung einer Nahrungsmittelallergie ausübt. Des Weiteren werden wir untersuchen ob eine Veränderung in der Komposition der Darmflora nach Induktion einer Nahrungsmittelallergie eine reine Konsequenz darstellt oder die Ursache einer allergischen Reaktion ist. Wir sind überzeugt, dass unsere Resultate einen wichtigen Beitrag zum Verständnis der Rolle der Mikrobiota in der Entstehung von Allergien leisten.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts: In den letzten 20 Jahren hat sich die Diagnose von Allergien verdoppelt. Die genauen Ursachen für dieses erhöhte Allergierisiko sind weitgehend unbekannt. Bestehende Therapien bekämpfen nur die Symptomatik einer allergischen Reaktion, nicht aber die Ursache. Deshalb ist es wichtig, neue therapeutische Ansätze zu entwickeln, welche die Entstehung einer allergischen Reaktion bereits im Keim ersticken. Ziel unserer Arbeit ist es daher neue Konzepte zur Ursachenbekämpfung allergischer Reaktionen zu erforschen.

 

 

 

Direct link to Lay Summary Last update: 27.08.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
High dietary fat intake induces a microbiota signature that promotes food allergy
Hussain Maryam, Bonilla-Rosso Germán, Kwong Chung Cheong K.C., Bäriswyl Lukas, Rodriguez Maria Pena, Kim Brian S., Engel Philipp, Noti Mario (2019), High dietary fat intake induces a microbiota signature that promotes food allergy, in Journal of Allergy and Clinical Immunology, na-na.
Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy.
Maryam Hussain, Loic Borcard, Maria Pena Rodriguez, Kevin P Walsh, Christoph Müller, Brian S Kim, Masato Kubo, David Artis, Mario Noti (2017), Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy., in Journal of Allergy and Clinical Immunology, S0091-6749.
The use of animal models to discover immunological mechanisms underpinning sensitization to food allergens
Joost J. Smit Mario Noti Liam O’Mahony (2016), The use of animal models to discover immunological mechanisms underpinning sensitization to food allergens, in Drug Discovery Today Disease Models, 17-18, 63-69.
New insights into basophil heterogeneity.
Oetjen LK Noti M Kim BS. (2016), New insights into basophil heterogeneity., in Seminars in Immunopathology, 549-561.
Current challenges facing the assessment of the allergenic capacity of food allergens in animal models.
Bøgh KL van Bilsen J Głogowski R López-Expósito I Bouchaud G Blanchard C Bodinier M Smit J P (2016), Current challenges facing the assessment of the allergenic capacity of food allergens in animal models., in Clin Transl Allergy, 13601.
CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis.
Brasseit J (2016), CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis., in Mucosal Immunology, 1-10.
Keeping bugs in check: The mucus layer as a critical component in maintaining intestinal homeostasis.
Faderl M (2016), Keeping bugs in check: The mucus layer as a critical component in maintaining intestinal homeostasis., in IUBMB Life, 275-285.
Epithelial-intrinsic IKKα expression regulates group 3 innate lymphoid cell responses and antibacterial immunity.
Giacomin PR (2015), Epithelial-intrinsic IKKα expression regulates group 3 innate lymphoid cell responses and antibacterial immunity., in Journal of Experimental Medicine, 1513-1528.
IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions.
Monticelli LA (2015), IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions., in PNAS, 10762-10767.
Dry roasting enhances peanut-induced allergic sensitization across mucosal and cutaneous routes in mice.
Moghaddam AE (2014), Dry roasting enhances peanut-induced allergic sensitization across mucosal and cutaneous routes in mice., in Journal of Allergy and Clinical Immunology, 1453-1456.

Collaboration

Group / person Country
Types of collaboration
Prof. Andrew Macpherson, Mucosal Immunology, DKF Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
PD Dr. Carsten Riether, DKF Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Prof. Jonathan Spergel, Childrens Hospital of Philadelphia United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr. Alexander Eggel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Johan Auwerx Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Thomas Brunner Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Prof. Brian S. Kim, Washington University United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
SGAI Annua Meeting Poster High dietary fat intake promotes food allergy 30.08.2018 Interlaken, Switzerland Hussain Maryam; Noti Mario;
EAACI Annual Congress Poster Basophil-derived IL-4 promotes epicutaneous allergen sensitization concomitant with the development of food allergy 17.06.2017 Helsinki, Finland Hussain Maryam; Noti Mario;
SGAI Annual Meeting Individual talk Basophil-derived IL-4 promotes epicutaneous allergen sensitization concomitant with the development of food allergy 01.06.2017 St.Gallen, Switzerland Hussain Maryam; Noti Mario;
Vertiefungskurs Individual talk Type-2 innate immune cells in allergic inflammation and beyond 12.05.2017 Konstanz, Germany Noti Mario;
Cost Action Imparas Individual talk Animal models of anaphylaxis 07.04.2017 Vienna, Austria Noti Mario;
World Immune Regulation Meeting (WIRM) Talk given at a conference Basophil-derived IL-4 promotes epicutaneous allergen sensitization concomitant with the development of food allergy 15.03.2017 Davos, Switzerland Noti Mario;
Invited Seminar: Institute of Physiology, University of Zurich Individual talk Type-2 Innate immune cells in allergic inflammation and beyond 08.02.2017 Zurich, Switzerland Noti Mario;


Self-organised

Title Date Place
2nd Type-2 Immunity Meeting Bern 15.12.2017 Bern, Switzerland
1st Type-2 Immunity Meeting Bern 16.12.2015 Bern, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Do Modern Lifestyles Cause Food Allergies? Scientia International 2017

Awards

Title Year
Best Poster Allergology: Annual Congress of the Swiss Society for Allergology and Immunology (SGAI), March 12-13, 2015, Basel 2015

Abstract

The Role of the Microbiota in Food-induced Allergic DisordersBackground: Food-induced allergic disorders (FIAD) have reached pandemic proportions, with an estimated 3-8% of children and adults in Westernized countries living with the daily concern that exposure to certain foods may trigger a life-threatening allergic reaction (1, 2) Currently, there is no cure for food allergies and available medications only treat symptoms after the allergic reaction occurs (3-5). As the public health and economic impact of FIAD continues to grow, there is an urgent need to develop new intervention strategies to prevent and treat these debilitating conditions. While the effector functions mediating food allergies are well described, little is known about the early immunological events that initiate these responses (6-8). Epidemiological studies have demonstrated that cutaneous inflammation associated with atopic dermatitis (AD) is a risk factor for the development of FIAD (9, 10). However, the immunological mechanisms through which antigen sensitization in the skin can predispose to allergic inflammation in the gastrointestinal tract are incompletely understood. Employing a new model of FIAD, my recent studies demonstrated that epicutaneous sensitization to food antigens on an AD-like skin lesion is associated with the infiltration of thymic stromal lymphopoietin (TSLP)-elicited basophils that promote the development of eosinophilic esophagitis (EoE)-like disease and IgE-mediated intestinal food allergy in response to oral antigen exposure (11). Importantly, TSLP-elicited basophil responses were necessary and sufficient for the development of FIAD. Applying a translational approach, we demonstrated that the TSLP-basophil axis is active in patients suffering from EoE, a food-allergy related disease characterized by dense infiltration of eosinophils into inflamed tissue. Further, we found that EoE patients with a polymorphism in the gene encoding for TSLP demonstrated with increased numbers of circulating basophils that positively correlated with the number of eosinophils in the esophageal biopsy. Together, my studies revealed that the TSLP-basophil axis mediates FIAD in a murine model system and is active in patients with EoE. Targeting the TSLP-basophil axis may offer a new therapeutic approach to treat FIAD. Although genetic predisposition is a significant risk factor for developing allergic inflammation, the skyrocketing increase in FIAD over the last three decades suggests that genetic predisposition alone cannot account for the observed phenomenon (12). Recent studies have highlighted that the trillions of bacteria hosting our body are not just hitchhikers, but actively communicate and contribute to the maturation of the host’s immune system (13-15). Alterations in dietary habits, vaccination, antibiotic usage, improved sanitary installations and limited exposure to infections associated with a Western lifestyle may significantly impact the composition of the host’s microbiota (16). There is good evidence from human and animal studies that the risk of allergy relates to a compromised commensal diversity (17, 18). Perturbations in this sophisticated immune-host-microbiota axis may cause dysregulated immune responses fostering the development of food-induced allergic inflammation (19). Understanding the mechanisms by which the microbiota shapes type-2 immune responses may lead to new treatment protocols to limit the development and progression of FIAD. Significance The prevalence of allergic reactions towards foods is continuously rising in developed countries and represents a significant economic burden. Recent work in the field of mucosal immunology demonstrates that alterations in the composition of the microbiota can favor the development of type-2 allergic inflammation. Applying a new-established model of FIAD and state-of-the-art methodologies, the proposed studies will shed light into the relationship and crosstalk between the microbiota and the host’s immune system including its susceptibility to allergic inflammation. Understanding the mechanisms by which microbial communities or microbial-derived metabolites shape type-2 immune responses will help in developing new therapeutic approaches to modulate allergic inflammation.
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