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Young Hyo Kim, MD, PhD Associate Professor, Department of Otolaryngology, Inha University College of Medicine, Incheon, Republic of Korea Vice-Director, Inha Institute of Aerospace Medicine, Inha University College of Medicine, Incheon, Republic of Korea Email: inhaorl@inha.ac.kr Objectives: Recent studies have advocated the use of probiotics to prevent and treat allergic diseases. However, the immunomodulatory effects and mechanism of probiotics in allergic airway disease are unknown. We studied whether Bacillus clausii (BC), a probiotic derived from mudflats, had anti-allergic effects and compared the results with those of Lactobacillus paracasei (LP). We also examined whether the anti-allergic mechanisms of probiotics are associated with hypoxia signaling. Methods: Forty-two BALB/c mice were randomly assigned to six experimental groups: normal controls, ovalbumin (OVA)-induced asthmatic mice, and OVA-induced mice orally administered with LP or BC, at 1×109 or 5×109 CFU/ml each. We performed differential cell count testing on bronchoalveolar lavage fluid (BALF), lung histopathology, serum total and OVA-specific IgE and IgG1, titer of Th2 cytokines (IL-4, IL-5) in BALF and pulmonary parenchyma, quantitative PCR for heme oxygenase (HO)-1 and Hif-1α, and immunohistochemistry for these mice. Results: Compared to the OVA group mice, OVAsensitized mice treated with LP or BC showed significantly reduced numbers of eosinophils and neutrophils in the BALF (P<0.05). Both probiotics also significantly reduced pulmonary inflammation and eosinophil infiltration. Mice in the LP or BC group had a substantially lower titer of IL-4 and IL-5 in BALF, and decreased IL-4 and IL-5 expression in the lung parenchyma. Real-time PCR and immunohistochemistry showed that both LP and BC could significantly suppress HO-1 and Hif-1α expression in asthmatic mice (P<0.05). Conclusion: BC can attenuate murine allergic asthma by regulating HIF-1α signaling, and its antiallergic effect is comparable to that of LP. Bacillus clausii, a Foreshore-derived Probiotic, Attenuates Allergic Airway Inflammation through Downregulation of Hypoxia Signaling Hyelim Park 1,2, Ah-Yeoun Jung1,2, Chung-Soon Chang3 and Young Hyo Kim1,2 1Department of Otorhinolaryngology, Head and Neck Surgery, 2Inha Institute of Aerospace Medicine, 3Department of Biochemistry, Inha University College of Medicine, Incheon, Republic of Korea

Bacillus clausii, a Foreshore-Derived Probiotic, Attenuates Allergic Airway Inflammation Through Downregulation of Hypoxia Signaling