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Hornef, Mathias; Pabst, Oliver; Annesi-Maesano, Isabella; Fleddermann, Manja; Mutius, Erika von; Schaubeck, Monika and Fiocchi, Alessandro (2021): Allergic diseases in infancy II-oral tolerance and its failure. In: World Allergy Organization Journal, Vol. 14, No. 11, 100586

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Objective: The early window of opportunity describes the timeframe after birth in which essential interactions of the immune system and the newly developing microbiota take place. The infant's immune system has to be reactive to invading pathogens and at the same time tolerant to dietary antigens. If the mechanisms of defense and tolerance induction are disturbed, the risk of infections or allergies is increased. Method: This is a narrative review of the recently published information on the topic of neonatal intestinal development and mechanisms of oral tolerance and summarizes the discussions and conclusions from the 8th Human Milk Workshop. Results: The early postnatal period sets the stage for life-long host-microbiome interaction. In this early phase, specific developmental mechanisms ensure physiologic interaction with the developing microbiota. Innate and adaptive immune cells interact in a concerted way to induce and uphold oral tolerance. Factors in human milk can support this induction of tolerance and simultaneously protect against infection and allergy development. Conclusion: Understanding the developmental mechanisms in this early phase of immune system development is the first step to develop strategies of pathology prevention. As human milk protects the infant from infections, and aids to develop a tolerogenic immune response, further knowledge on the protective factors in human milk and their effect on the immune system is required.

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