British Journal of Nutrition

Workshop Report

Early nutrition and immunity – progress and perspectives

Philip C. Caldera1 c1 c2, Susanne Krauss-Etschmanna2a3 c2, Esther C. de Jonga4, Christophe Duponta5, Julia-Stefanie Fricka6, Hanne Frokiaera7, Joachim Heinricha8, Holger Garna9, Sibylle Koletzkoa10, Gideon Lacka11, Gianluca Mattelioa12, Harald Renza9, Per T. Sangilda13, Jürgen Schrezenmeira14, Thomas M. Stulniga15, Thomas Thymanna13, Agnes E. Wolda16 and Berthold Koletzkoa17

a1 Institute of Human Nutrition, School of Medicine, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK

a2 Clinical Cooperation Group ‘Pediatric Immune Regulation’, Dr von Hauner Children's Hospital, University of Munich, Linderwurmstrasse, D-80337 Munich, Germany

a3 GSF-National Research Center for Environment and Health, Ingolstadter Lanstrasse, D-85758 Neuherberg, Germany

a4 Departments of Cell Biology & Histology and Academic Medical Centre, University of Amsterdam, Meiberjdreef, 1105AZ Amsterdam, The Netherlands

a5 Department of Pediatric Gastroenterology and Nutrition Unit, Cochin-Saint Vincent de Paul Hospital, University Paris V – René Descartes, Av. Denfirt-Rochereau, 75014 Paris, France

a6 Department of Medical Microbiology and Hygiene, University of Tübingen, Elfriede-Aulhornstrasse, D-72076 Tübingen, Germany

a7 BioCentrum-DTU, Biochemistry and Nutrition, Technical University of Denmark, Kgs. Lyngby, DK-2800, Denmark

a8 Institute of Epidemiology, GSF-National Research Centre for Environment and Health, Ingolstadter Lanstrasse, D-85758 Neuherberg, Germany

a9 Department of Clinical Chemistry and Molecular Diagnostics – Central Laboratory, Philipps-University of Marburg, Nans-Meerwinstrase, D-35043 Marburg, Germany

a10 Division of Gastroenterology, Dr von Hauner Children's Hospital, University of Munich, Linderwurmstrasse, D-80337 Munich, Germany

a11 Pediatric Allergy and Clinical Immunology, Imperial College School of Medicine at St Mary's Hospital, Praed Street London W2 1NY, UK

a12 Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti, 20141 Milan, Italy

a13 Department of Human Nutrition, The Royal Veterinary and Agricultural University, Rolighedsvej, DK-1958 Frederiksberg, Denmark

a14 Institute for Physiology and Biochemistry of Nutrition, Federal Research Centre for Nutrition and Food, Hermann-Weigmannstrasse, D-24103 Kiel, Germany

a15 Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Wahringer Gurtel, 1090 Vienna, Austria

a16 Department of Clinical Bacteriology, The Sahlgrenska Academy at Göteborg University, Guldhegsgaten, S-41346 Göteborg, Sweden

a17 Division of Metabolic Diseases and Nutritional Medicine, Dr von Hauner Children's Hospital, University of Munich, Linderwurmstrasse, D-80337 Munich, Germany

Abstract

The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to ‘self’, to food and other environmental components, and to commensal bacteria. A breakdown in the tolerogenic pathways can also lead to inflammatory diseases. The prevalence of inflammatory diseases, including atopic disorders, has increased over the last 60 years. The development of tolerance is the result of active immune mechanisms and both development and maintenance of tolerance are lifelong processes which start very early in life, even prenatally. Profound immunologic changes occur during pregnancy, involving a polarization of T helper (Th) cells towards a dominance of Th2 and regulatory T cell effector responses in both mother and fetus. This situation is important to maintain pregnancy through avoidance of the rejection of the immunologically incompatible fetus. During the third trimester of human pregnancy, fetal T cells are able to mount antigen-specific responses to environmental and food-derived antigens and antigen-specific T cells are detectable in cord blood in virtually all newborns indicating in utero sensitization. If the neonatal immune system is not able to down-regulate the pre-existing Th2 dominance effectively then an allergic phenotype may develop. Changes occur at, and soon after, birth in order that the immune system of the neonate becomes competent and functional and that the gut becomes colonized with bacteria. Exposure to bacteria during birth and from the mother's skin and the provision of immunologic factors in breast milk are amongst the key events that promote maturation of the infant's gut and gut-associated and systemic immune systems. The introduction of formula and of solid foods exposes the infant to novel food antigens and also affects the gut flora. Nutrition may be the source of antigens to which the immune system must become tolerant, provide factors, including nutrients, that themselves might modulate immune maturation and responses, and provide factors that influence intestinal flora, which in turn will affect antigen exposure, immune maturation and immune responses. Through these mechanisms it is possible that nutrition early in life might affect later immune competence, the ability to mount an appropriate immune response upon infection, the ability to develop a tolerogenic response to ‘self’ and to benign environmental antigens, and the development of immunologic disorders. A Workshop held in February 2006 considered recent findings in the areas of oral tolerance, routes of sensitization to allergens and factors affecting the development of atopic disease; factors influencing the maturation of dendritic cells and the development of regulatory T cells; the influence of gut microflora on immunity, allergic sensitization and infectious disease; the role of nutrition in preventing necrotizing enterocolitis in an animal model of preterm birth; and the role of PUFA of different classes in influencing immune responses and in shaping the development of atopic disease. This report summarizes the content of the lectures and the subsequent discussions.

(Received June 23 2006)

(Accepted June 23 2006)

Correspondence:

c1 *Corresponding author: Dr Philip C. Calder, fax +44 (0)2380 594379, email pcc@soton.ac.uk

c2 Authors made an equal contribution to the writing of this report.

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