Abstract

Asthma is a chronic respiratory disease highly prevalent worldwide. Recent studies have suggested a role for microbiome-associated gut–lung axis in asthma development. In the current study, we investigated if Resveratrol (RES), a plant-based polyphenol, can attenuate ovalbumin (OVA)-induced murine allergic asthma, and if so, the role of microbiome in the gut–lung axis in this process. We found that RES attenuated allergic asthma with significant improvements in pulmonary functions in OVA-exposed mice when tested using plethysmography for frequency (F), mean volume (MV), specific airway resistance (sRaw), and delay time(dT). RES treatment also suppressed inflammatory cytokines in the lungs. RES modulated lung microbiota and caused an abundance of Akkermansia muciniphila accompanied by a reduction of LPS biosynthesis in OVA-treated mice. Furthermore, RES also altered gut microbiota and induced enrichment of Bacteroides acidifaciens significantly in the colon accompanied by an increase in butyric acid concentration in the colonic contents from OVA-treated mice. Additionally, RES caused significant increases in tight junction proteins and decreased mucin (Muc5ac) in the pulmonary epithelium of OVA-treated mice. Our results demonstrated that RES may attenuate asthma by inducing beneficial microbiota in the gut-lung axis and through the promotion of normal barrier functions of the lung.

Highlights

  • We found that RES attenuated allergic asthma with significant improvements in pulmonary functions in OVA-exposed mice when tested using plethysmography for frequency (F), mean volume (MV), specific airway resistance, and delay time(dT)

  • The data showed that after Mch exposure, the Ova-veh group showed an increase in to exhale (Te) but not in other parameters when compared to the naïve group, Ova-res group showed increases in sGaw, peak of expiratory flow (PEF), and a decrease in to inhale (Ti) and Te when compared to the Ova-veh group (Figure S1C)

  • These data together suggested that the lung functions as measured by specific airway conductance, airway resistance, and time to inhale and exhale, significantly improved following treatment of mice exhibiting Ova-induced asthma, with resveratrol

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Summary

Introduction

It is one of the most common chronic respiratory diseases seen globally. It affects over 300 million people globally and its incidence continues to grow [2]. Asthma is considered to be a heterogeneous disease with multiple immunological pathways involved. The well-characterized pathway includes the activation of excessive T-helper type 2 (Th2) cells along the bronchial airways and massive production of pro-inflammatory Th2 cytokines such as IL-4, IL-5 and IL-13 [4]. The release of Th2 cytokines during an asthma attack initiates a cascade of inflammatory responses along the barrier sites of the pulmonary system [4, 5]

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