Effects of inter-alpha-trypsin inhibitor heavy chain 4 on microbiome in OVA-induced asthma mouse

<bold>Backgrounds:</bold> Asthma is a chronic inflammatory disease of the airway. The objective of the study is to investigate the role of ITIH4 on gut and lung microbiome in OVA-induced asthma mice. <bold>Methods:</bold> An asthma model was established by intraperitoneal administration of 50μg/kg OVA to six-week-old BALB/c mice weekly for 4 weeks. Control mice received PBS under the same conditions. After 4 weeks, the OVA mice received intranasal administration of 0 (PBS), 1.25, or 2.5 μg/mL ITIH4 for 7 days. Mice were then challenged intranasally with 100 μg/kg OVA for 3 days. We collected bronchoalveolar lavage fluid and lung samples to analyze inflammatory responses. Lung and intestinal tissues were collected for 16S rRNA sequence analysis. Additionally, we measured body weight, exercise oxygenation, lung function, and serum IgE levels. <bold>Results:</bold> ITIH4 administration reduced airway resistance, inflammation, and IgE in the OVA-induced asthma mice. The Principal Co-ordinates Analysis (PCoA) results showed differences between lung and gut microbiota community structures. The phylum of microbiota in both the lung and gut is dominated by bacteroidota and firmicutes. We discovered that the ITIH4-treated group has higher Firmicutes abundance in the lung, but lower in the gut, compared to the OVA group. <bold>Conclusion:</bold> The results suggest that ITIH4 is related to the phylum firmicutes in OVA-induced asthma mice, resulting in decreased airway inflammation.