Antibiotic administration aggravates asthma by disrupting gut microbiota and the intestinal mucosal barrier in an asthma mouse model.

In humans, gut microbiota can determine the health status. The regulatory mechanisms of the gut microbiota in asthma must be elucidated. Although antibiotics (ABXs) can clear infections, they markedly alter the composition and abundance of gut microbiota. The present study used ABX-treated mice to examine the time-dependent effects of ABX administration on the gut microbiota and intestinal mucosal barrier. The mouse asthma model was established using ovalbumin (OVA) and gavaged with an ABX cocktail for different durations (1 or 2 weeks) and stacked sequences. The pathology of the model, model 2, OVA-ABX, OVA-ABX 2, ABX-OVA and ABX-OVA was severe when compared with the control group as evidenced by the following results: i) significantly increased pulmonary and colonic inflammatory cell infiltration; ii) enhanced pause values and iii) OVA-induced immunoglobulin E (IgE) and TGF-β expression levels, and significantly downregulated Tight Junction Protein 1 (TJP1), claudin 1 and Occludin expression levels. Furthermore, the intestinal bacterial load in the OVA-ABX and OVA-ABX 2 groups was significantly lower than that in the ABX-OVA and ABX-OVA 2 groups, respectively. The predominant taxa were as follows: phyla, Firmicutes and Proteobacteria , genera, Escherichia - Shigella , Lactobacillus and Lachnospira . The abundances of Lachnospira and Escherichia - Shigella were correlated with the expression of OVA-induced IgE and TJPs. These findings indicated that ABX administration, which modifies microbiome diversity and bacterial abundance, can disrupt colonic integrity, downregulate TJ proteins, damage the intestinal barrier, enhance enterocyte permeability, and promote the release of inflammatory factors, adversely affecting asthma alleviation and long-term repair.