Dietary 3'-sialyllactose reduces sensitization and type 2 inflammation in a house dust mite induced acute allergic asthma model

Marit Zuurveld^1*Janna De Kleer¹Ingrid Van Ark¹Thea Leusink-Muis¹Atanaska Kostadinova²Johan Garssen^1,2Gert Folkerts¹Belinda van't Land^2,3Linette Willemsen¹

• ¹Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht University, Utrecht, Netherlands, Netherlands
• ²Danone Research & Innovation, Utrecht, Netherlands
• ³Center for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands, Netherlands

Allergic asthma affects over 300 million people globally, characterized by a type 2 immune response to allergens like house dust mite (HDM). This includes eosinophilia, IgE production, and symptoms such as bronchial hyperresponsiveness. Human milk oligosaccharides (HMOS), ingested by breastfed infants, have immunomodulatory effects and may help prevent allergic diseases, like asthma. This study investigates the effects of two sialylated HMOS, 3'-sialyllactose (3'SL) and 6'-sialyllactose (6'SL), in a murine model of HDM-induced allergic asthma. Male BALB/c mice (6-7 weeks old) were fed an AIN93G diet with or without 0.1% or 0.5% 3'SL or 6'SL from 2 weeks before HDM sensitization until sacrifice. Airway hyperresponsiveness was measured after the final HDM challenge, and broncho-alveolar lavage fluid (BALF) and lung tissue were collected for analysis. Dietary 0.5% 3'SL, 0.1% 6'SL, or 0.5% 6'SL prevented methacholine-induced airway hyperresponsiveness in HDM-challenged mice compared to control diet. Mice fed the 0.5% 3'SL diet had elevated SCFA levels in cecum content. Both 3'SL and 6'SL groups showed reduced HDM-induced macrophage influx in BALF. Mice on 3'SL diets had lower total inflammatory cell influx, while those on 0.5% 6'SL had increased eosinophils in BALF, associated with higher IL33, TNFα, CCL5, IFNγ levels, and reduced regulatory T cells. The 3'SL diets also prevented increases in HDM-specific IgE and mMCP1 in serum. Dietary 3'SL and 6'SL showed dose-dependent, differential clinical and immunological outcomes in HDM-sensitized mice. Both 0.5% 3'SL, 0.1% 6'SL, and 0.5% 6'SL reduced airway hyperresponsiveness. However, 0.5% 6'SL increased eosinophilic inflammation, while 3'SL protected against HDM-induced sensitization and asthma development.