Exacerbation of Asthma Airway Inflammation by HOCl Exposure: Insights from Fecal Microbiota and Metabolomics

Abstract

Environmental pollutant exposure has been demonstrated to be associated with the onset and progression of asthma. Hypochlorous acid (HOCl), as an environmental exposure-relevant chlorine-based disinfectant, its role in asthmatic airway inflammation remains unclear. Through administering HOCl in drinking water during early life and the perinatal period, we discovered that early-life HOCl drinking water exposure not only aggravated airway inflammation in asthmatic mice but also that perinatal HOCl drinking water exposure could promote airway inflammation in the offspring of asthmatic mice. By gut microbiota sequencing, it was found that HOCl drinking water exposure could reduce the gut microbiota diversity in asthmatic mice, with the abundances of Lactobacillus, Faecalibaculum, Muribaculum, and [Eubacterium]_ventriosum_group being decreased, while increasing the abundances of Dubosiella and Parabacteroides. Further fecal metabolomics analysis revealed that HOCl drinking water exposure significantly enhanced the arachidonic acid metabolism pathway. And there was a certain correlation between the abundances of the significantly altered bacterial genera and the levels of arachidonic acid metabolites. Finally, treatment with taurine, a HOCl neutralizer, showed that taurine could significantly alleviate the asthma airway inflammation aggravated by HOCl exposure. In summary, these results provide evidence for the exacerbation of asthma airway inflammation by HOCl exposure and confirm that taurine supplementation can serve as a potential therapeutic approach.