The Protective Potential of Fructo-oligosaccharides in Allergic Airway Inflammation: From Gut to Lung in Preclinical Models

Allergic asthma is a chronic lung disease that affects millions of people worldwide. It is often triggered by allergens such as house dust mite and leads to lung inflammation and breathing difficulties. This dissertation investigated whether dietary fibers, specifically fructo-oligosaccharides (FOS) found in fruits, vegetables, and grains, can help reduce asthma-like symptoms. The underlying hypothesis is that FOS can influence the gut microbiota, and that beneficial gut bacteria can ferment FOS into short-chain fatty acids (SCFAs)—acetate, propionate, and butyrate—that may suppress airway inflammation. The research program combined in vitro cell culture studies using human lung epithelial cells with a model for allergic asthma in mice. The in vitro studies demonstrated that butyrate could protect bronchial epithelial cells against barrier damage and inflammatory signals induced by house dust mite exposure. In mice, it was observed that the balance of SCFAs differs across body compartments such as the gut, blood, and lungs, with lung-specific acetate levels being particularly reduced in allergic asthma. In house dust mite-allergic mice, the effects of dietary supplementation with two ratios of short- and long-chain FOS, as well as different FOS dosages, were assessed on allergic airway inflammation. Results showed that FOS, depending on ratio and dose, could alter gut microbiota composition, modulate SCFA levels, and shift immune responses, thereby reducing type 2 allergic inflammation. However, even the highest FOS dose (10%) could not prevent allergic airway inflammation. This dissertation demonstrates that FOS can influence gut microbiota, immune responses, and lung health. Although FOS did not prevent development of house dust mite-induced asthma, it did protect against allergic type 2 immune activation. FOS supplementation therefore warrants further investigation as a potential supportive strategy in the management of allergic asthma. This work also highlights the importance of a fiber-rich diet in supporting the microbiome, immune system, and respiratory function.