Human milk inspired oligosaccharides for allergy prevention

Differential immunomodulatory effects of fucosylated and sialylated human milk oligosaccharides in preclinical in vivo models and novel developed human mucosal in vitro models for food allergy or allergic asthma prevention

Short summary:
Utrecht University (Pharmacology) and Danone Nutricia Research B.V. (Immunology platform) collaborated to obtain novel insights in the immunomodulatory properties of several types of HMOS that have recently become available on industrial scale. Proper early life immune development is important to reduce the risk on developing allergies. In the current project, advanced in vitro human mucosal immune models of the gut and lung have been developed. In these and already established models, several fucosylated and sialylated HMOS showed strong and differential immunomodulatory properties. This was also observed in preclinical in vivo models for food allergy and allergic asthmaindicating allergy preventive properties of specific HMOS.

Societal/economic impact:
Food allergy and allergic asthma seriously affect the wellbeing of the affected infant and its caregivers and is a considerable economic problem. For cow’s milk allergy only in the USA $24.8 billion is spent annually and in The Netherlands the costs for asthma will rise to 170-180 million euros in 2025. Prevention of food allergy and allergic asthma in early life may provide lifelong benefits, since majority of asthma cases origin from childhood and early life food allergy predisposes for allergic asthma development.

Project’s approach and output:
This project yielded novel developed advanced in vitro human mucosal immune models of the gut and skin. These will be further developed and validated and to study allergy preventive effects of dietary components. This allows to reduce use of animal testing. The strong immunomodulatory properties shown for the different HMOS build body of evidence for use in novel infant formula’s mimicking more closely the composition human milk with possible added benefit of lowering early life allergy risk.    

Project deliverables:
1) Developed advanced in vitro human mucosal immune models (gut and lung).

2) Shown differential immunomodulatory properties of HMOS for allergy prevention and immune development (in vitro). 

3) Shown differential immunomodulatory and allergy preventive effects of HMOS for food allergy and asthma (in vivo).

4) Four peer reviewed scientific papers, and an additional 4 to be submitted shortly.

5) Possible patent opportunity under investigation.

6) PhD candidate will defend her thesis end this year/early next year.

7) PhD candidate has received basic qualification teaching certificate and teaching (UU).

8) Post doc contract for PhD candidate at UU financed by Danone Nutricia Research.

LSHM18037

Summary
Human milk oligosaccharides (HMOS) are important in early life immune development. In this project, differential immunomodulatory effects of several commercially available HMOS were identified in advanced human gut and lung in vitro mucosal immune models and in vivo models for food allergy and allergic asthma, indicating their allergy preventive properties.
Technology Readiness Level (TRL)
4 - 6
Time period
53 months
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