Early Life Exposure to Human Milk Oligosaccharides Reduces Allergic Response in a Murine Asthma Model

BACKGROUND: Studies suggest that early-life gut microbiota composition and intestinal short-chain fatty acids (SCFAs) are linked to future asthma susceptibility. Furthermore, infancy offers a critical time window to modulate the microbiota and associated metabolites through diet-microbe interactions to promote infant health. Human milk oligosaccharides (HMOs), nondigestible carbohydrates abundant in breast milk, are prebiotics selectively metabolized by gut microbiota that consequently modify microbiome composition and SCFA production. METHODS: Using a house dust mite mouse model of allergy, we investigated the impacts of early oral treatment of pups with biologically relevant doses of 2′-fucosyllactose (2′-FL) and 6′-sialyllactose (6′-SL), two of the most abundant HMOs in human milk, in amelioration of allergic airway disease severity. RESULTS: We found that administration of 2′-FL and 6′-SL during early life reduced lung histopathology scores, circulating IgE, cytokine levels, and inflammatory cell infiltration, all hallmark symptoms of allergic asthma. HMO supplementation also increased the relative abundance of intestinal Bacteroidetes and Clostridia, known SCFA producers within the gut. Indeed, we detected increased SCFA concentrations in both the intestine and blood of adult mice who received HMOs prior to weaning. CONCLUSION: We propose a model in which orally administered HMOs delivered during early life shift the microbiota toward increased production of SCFAs, which dampens the allergic immune responses behind allergy and asthma. Overall, these data suggest the potential for HMO supplementation to protect infants against asthma development later in life, with possible benefits against additional atopic diseases such as eczema and food allergies.