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Intestinal Microflora Altered by Vancomycin Exposure in Early Life Up-regulates Type 2 Innate Lymphocyte and Aggravates Airway Inflammation in Asthmatic Mice

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Abstract

Allergic asthma is a chronic inflammatory disease primarily mediated by Th2 immune mechanisms. Exposure to antibiotics during early life is associated with an increased risk of allergic asthma, although the exact mechanism is not fully understood. In this study, mice were randomly divided into a normal saline control group (NS group), an OVA-induced asthma group (OVA group), a vancomycin treatment control group (VAN.NS group), and a vancomycin treatment the OVA-induced asthma group (VAN.OVA group). The results showed that vancomycin altered dominant species in experimental mice. The phylum level histogram showed that Bacteroides abundance was increased, and Firmicutes abundance was decreased in the OVA group. Airway inflammation and airway hyperresponsiveness (AHR) were aggravated in the vancomycin-exposed group. Enzyme-linked immunosorbent assay (ELISA) showed that the serum levels of IL-5, IL-13, and IL-33 in the OVA group were higher than those in the NS group, especially in the VAN.OVA group. The expression of GATA binding protein-3(GATA3) and retinoid acid receptor-related orphan receptor alpha (RORa) increased in the OVA group, even more so in the VAN.OVA group. Group 2 innate lymphoid cells (ILC2s) in the lung detected by flow cytometry was increased in OVA mice more than those in control mice, with a more remarkable increase in the VAN.OVA. Our results demonstrated that vancomycin used in early life could alter the intestinal microecology of mice, which, in turn, aggravates airway inflammation and upregulate type 2 innate lymphocytes.

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Funding

This work was supported by 1. Wenzhou Municipal Science and Technology Bureau (Y20210007). 2. Zhejiang Medical and Health Major Projects of Science and Technology (WKJ-ZJ-2133).

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Authors and Affiliations

  1. Department of Pediatric Allergy and Immunology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Xueyuan West Road 109, Wenzhou, 325027, China

    Qiangwei Xiang, Hang Zheng, Like Wang, Jinyi Wan & Weixi Zhang

  2. Department of Pediatric Gastroenterology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, China

    Xiumei Yan

  3. Department of Pharmacy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, China

    Xixi Lin

  4. The Second Clinical Medical College, Wenzhou Medical University, 270 West Xueyuan Road, Zhejiang Province, Wenzhou, 325027, China

    Wei Zhao

  5. Department of Allergy and Immunology for Clinical Operation, Department of Pediatrics, Virginia Commonwealth University, Richmond, VA, 23298, USA

    Wei Zhao

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  1. Qiangwei Xiang
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Contributions

Qiangwei Xiang wrote the paper. Wei Zhao, Weixi Zhang design and edited the paper. Methodology, Like Wang, Jinyi Wan, Hang zheng. formal analysis, Xiumei Yan, data curation, Xixi lin. All authors read, revised and approved the final manuscript.

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Correspondence to Wei Zhao or Weixi Zhang.

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The study protocol was approved by Wenzhou Medical University Ethics Committee of Animal Experiments (ID Number: wydw 2020–0778).

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Xiang, Q., Yan, X., Lin, X. et al. Intestinal Microflora Altered by Vancomycin Exposure in Early Life Up-regulates Type 2 Innate Lymphocyte and Aggravates Airway Inflammation in Asthmatic Mice. Inflammation 46, 509–521 (2023). https://doi.org/10.1007/s10753-022-01748-4

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