A Specific Ratio of Dietary Short-Chain and Long-Chain Fructo-Oligosaccharides Shifts the Immune Response Away from Type 2 in a Murine Model for House Dust Mite-Induced Asthma

<b>Background/Objectives</b>: The gut microbiome has an important role in immune regulation, and dietary interventions that support a balanced microbiota may help to prevent the development of allergic asthma. Dietary fibers can beneficially affect the intestinal microbiome, but due to the diversity of fiber types, the effects differ. In this study, we investigate the preventive effects of two mixes of short-chain and long-chain (1:1 and 9:1 ratio) fructo-oligosaccharides (FOS) in a mouse model of house dust mite (HDM)-induced allergic asthma. <b>Methods</b>: BALB/c mice received FOS-supplemented (1% <i>w</i>/<i>w</i>) diets before and during intranasal exposures to HDM. Endpoint airway hyperreactivity measurements were performed, followed by the collection of bronchoalveolar lavage fluid (BALF), lung, serum and cecum content. Fecal microbiome composition was determined by DNA sequencing and short-chain fatty acid (SCFA) levels were determined in the cecum, serum and lung. <b>Results</b>: Fecal microbiome analyses revealed an increased abundance of <i>Prevotellaceae</i> after FOS1:1 supplementation in HDM-allergic mice. Additionally, FOS1:1 protected against an HDM-induced increase in basal airway resistance. Both FOS1:1 and FOS9:1 restored the systemic acetate levels in HDM-allergic mice. The two FOS supplementations did not affect HDM-induced inflammatory cell influx in the BALF. However, FOS1:1 increased the frequency of Th1-cells and prevented an HDM-induced increase in the Th2/Th1 balance. Upon ex vivo restimulation with HDM, lung cell suspensions of FOS1:1-fed mice produced less type 2-related cytokines compared to control-supplemented mice, and FOS9:1 followed a similar pattern. <b>Conclusions</b>: Specific short-chain and long-chain FOS ratios differentially affect the microbiome and immune system in a mouse model with HDM-induced allergic airway inflammation. Dietary supplementation with FOS1:1 shifts the immune response away from type 2, suggesting that dietary fibers like FOS1:1 may contribute as a part of a broader strategy to modulate HDM-induced allergic asthma.