Dietary fructo-oligosaccharides dose-dependently modulate the microbiome and suppress type 2 lung inflammation in a murine model of house dust mite-induced allergic asthma

Introduction A balanced microbiome is crucial for local and systemic immune regulation. Dietary fibers can support the intestinal microbiome, protecting the host from allergic diseases, including asthma. The effects of fibers depend on their type, dose, and disease context. Here, we investigated the preventative effects of four doses of fructooligosaccharides (FOS) in a murine model for house dust mite (HDM)-induced allergic asthma. Methods BALB/c mice received a diet containing 1%, 2.5%, 5%, or 10% FOS (w/w) both prior to and during sensitization and challenges with HDM. Bronchoalveolar lavage fluid (BALF), lung tissue, serum, and cecum content were collected at the endpoint. Fecal microbiome composition was analyzed, and levels of short-chain fatty acids (SCFAs) were measured in cecum content, serum, and lung samples. Results HDM-allergic mice showed eosinophilic airway inflammation and increased pulmonary type 2 inflammation, while cecal SCFA levels were lower compared to sham mice. Serum acetate concentrations showed a similar decline ( p = 0.092). The 10% FOS diet did not prevent allergic sensitization or eosinophilic airway inflammation; however, it significantly reduced the proportions of T helper 2 (Th2) cells and the Th2/Th1 ratio in the lungs, decreased concentrations of chemokine (C-C motif) ligand 2 (CCL22) and interleukin (IL-13) in the BALF, and inhibited IL-13 production upon ex vivo HDM restimulation of lung cells. The 2.5% and 5% FOS diets also decreased Th2 cell frequency in the lungs. High doses of FOS increased the abundance of fecal Prevotellaceae , while reducing fecal Oscillospiraceae and Lactobacillaceae . These microbial shifts were correlated with protective effects against type 2 inflammation. In HDM-allergic mice, fecal Prevotellaceae abundance correlated positively with serum acetate concentrations, which were correlated with type protective effects. In allergic mice, the 2.5% and 5% FOS doses were associated with increased abundance of fecal Muribaculaceae and Bacteroidaceae , respectively, along with elevated cecal SCFA concentrations. In addition, the 5% FOS dose increased the relative abundance of fecal Lachnospiraceae , which correlated negatively with serum acetate levels and type prevention. Discussion Dietary FOS modulated the gut microbiome and attenuated pulmonary type 2 immune responses in a dose-dependent manner. These findings underscore the importance of fiber dosing for precision nutrition strategies in allergy management.