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HMOS 2'FL and 3FL prevent house dust mite induced proinflammatory cytokine release in vitro and decrease specific IgE

Marit Zuurveld¹, Janna W M de Kleer¹, Alinda J Berends¹

¹Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Science, Utrecht University, Utrecht, Netherlands.

Frontiers in Nutrition

|March 6, 2025

Summary

Human milk oligosaccharides (HMOS), specifically 2'-fucosyllactose (2'FL) and 3-fucosyllactose (3FL), show potential in preventing allergic asthma. These compounds modulated immune responses in vitro and reduced specific IgE in a mouse model, though airway inflammation was not prevented.

Area of Science:

Immunology
Allergy Research
Microbiome and Immune Development

Background:

Allergic asthma is a significant health concern, often triggered by allergens like house dust mite (HDM).
Human milk oligosaccharides (HMOS) are known to influence immune system development and may play a role in allergy prevention.

Purpose of the Study:

To establish a human in vitro model for studying HDM-induced allergic asthma.
To investigate the immunomodulatory effects of HMOS, specifically 2 -fucosyllactose (2 'FL) and 3-fucosyllactose (3FL), on allergic responses.
To evaluate the efficacy of HMOS in a murine model of HDM-induced allergic asthma.

Main Methods:

Developed a human in vitro model involving bronchial epithelial cells (BECs), monocyte-derived dendritic cells (moDCs), and T cells exposed to HDM.
Investigated the effects of 2 'FL and 3FL on this in vitro model.
Administered 2 'FL and 3FL to mice in a HDM-induced allergic asthma model.

Main Results:

HDM exposure in the in vitro model increased TSLP and IL4, indicative of a type 2 immune response, while reducing TGFβ.
Preincubation with 2 'FL or 3FL inhibited HDM-induced TSLP and IL8 release from BEC-DC co-cultures.
Mice fed diets supplemented with 2 'FL or 3FL exhibited lower serum levels of HDM-specific IgE compared to controls.
Despite reduced IgE, HMOS supplementation did not protect against airway inflammation in the murine model.

Conclusions:

Successfully established a human in vitro model for HDM sensitization, reducing the need for animal testing.
HMOS (2 'FL and 3FL) demonstrated an ability to shift immune responses away from a type 2 signature both in vitro and in vivo.
Fucosylated HMOS warrant further investigation for their potential in preventing HDM-allergic asthma.

Keywords:

advanced in vitro models allergic asthma allergy prevention human milk oligosaccharides mucosal inflammation

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