Azithromycin pretreatment exacerbates atopic dermatitis in trimellitic anhydride-induced model mice accompanied by correlated changes in the gut microbiota and serum cytokines.

Huawei Zhao, Jia Zhou, Haimei Lu, Anran Xi, Mengxian Luo, Keer Wang, Hongjie Lv, Huijuan Wang, Ping Wang, Jing Miao, Zhenghao Xu

International immunopharmacology 2022 Jan

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Atopic dermatitis (AD) is a common inflammatory skin disease. This study aims to investigate the effect of azithromycin (AZI) pretreatment, a common macrolide-type antibiotic, on the trimellitic anhydride (TMA) induced AD-like symptoms in mice. AZI (25 mg/kg, once daily, 5 days) was administered intragastrically before the 10-day TMA challenge. AD-like symptoms were assessed by ear thickening, scratching behavior, and pathological or immunofluorescence staining; Cytokines in the skin tissue and serum were measured by cytometric bead array; and the compositions of gut microbiota were assessed by 16S rRNA gene sequencing. AZI pretreatment accelerated the development of ear thickening and enhanced the severity of developed AD-like symptoms. AZI pretreatment promoted the infiltrations of neutrophil-like cells, T cells, and mast cells in ear skin. AZI pretreatment elevated the levels of IL-4, IL-6, and IL-17A in the ear skin of AD model mice, but it increased serum TNF-α and IL-6. AZI-pretreatment increased four gut bacterial genera (Bacteroides, Candidatus_Saccharibacteria_unclassified, Acetatifactor, Firmicutes_unclassified) but depleted three short-chain fatty acids producing gut bacterial genera (Alistipes, Clostridiales_unclassified, Butyricicoccus). AD-associated symptoms were positively associated with skin IL-4 and IL-17A, serum TNF-α, and IL-6, and Acetatifactor, but they negatively correlated to the three decreased gut bacterial genera (Alistipes, Clostridiales_unclassified, Butyricicoccus). Thus, our results demonstrate that AZI exposure deteriorates TMA-induced AD-like symptoms in mice, which is related to the imbalances of gut microbiota and skin/serum cytokines. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Huawei Zhao, Jia Zhou, Haimei Lu, Anran Xi, Mengxian Luo, Keer Wang, Hongjie Lv, Huijuan Wang, Ping Wang, Jing Miao, Zhenghao Xu. Azithromycin pretreatment exacerbates atopic dermatitis in trimellitic anhydride-induced model mice accompanied by correlated changes in the gut microbiota and serum cytokines. International immunopharmacology. 2022 Jan;102:108388