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

Abstract

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. Effects of fibers depend on type, dose and disease context. Here, we investigated the preventative effects of four doses of fructo-oligosaccharides (FOS) in a murine model for house dust mite (HDM)-induced allergic asthma. BALB/c mice received a diet with 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 caecum content were collected at the endpoint. Faecal microbiome composition was analyzed, and levels of short-chain fatty acids (SCFA) were measured in caecum content, serum and lung samples. 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 the same declining tendency (p=0.092). The 10% FOS diet did not protect from allergic sensitization or eosinophilic airway inflammation, however it did reduce the proportions of Th2 cells and the Th2/Th1 ratio in the lungs, the concentrations of CCL22 and 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 lung. High doses of FOS increased the abundance of faecal Prevotellaceae, while reducing faecal Oscillospiraceae and Lactobacillaceae. These microbial shifts were correlated with protective effects against type 2 inflammation. In HDM allergic mice, faecal Prevotellaceae abundance correlated positively with serum acetate concentrations, which were correlated with type 2 protective effects. In allergic mice, the 2.5% and 5% FOS dose were associated with increased abundance of faecal Muribaculaceae and Bacteroidaceae respectively along with elevated cecal SCFA concentrations. In addition, the 5% FOS dose increased the relative abundance of faecal Lachnospiraceae, which correlated negatively with serum acetate levels and type 2 prevention. Dietary FOS modulated the gut microbiome and ameliorated pulmonary type 2 immune responses in a dose-dependent manner. This underscores the critical role of fiber dosing in paving the way for precision nutrition in allergy management.