Allergic Airway Inflammation Emerges from Gut Inflammation and Leakage in Mouse Model of Asthma

Abstract

Asthma is an allergic airway inflammatory disease characterized by type 2 immune responses. Growing evidence suggests an association between allergic airways and intestinal diseases. However, the primary site of disease origin and initial mechanisms involved in the development of allergic airway inflammation (AAI) is not yet understood. Therefore, the initial contributing organs and mechanisms involved in the development of AAI are investigated using a mouse model of asthma. This study, without a local allergen challenge into the lungs, demonstrates a significant increase in intestinal inflammation with signature type‐2 mediators including IL‐4, IL‐13, STAT6, eosinophils, and Th2 cells. In addition, gut leakage and mRNA expressions of gut leakage markers significantly increase in the intestine. Moreover, reduced mRNA expressions of tight junction proteins are observed in gut and interestingly, in lung tissues. Furthermore, in lung tissues, an increased pulmonary barrier permeability and IL‐4 and IL‐13 levels associated with significant increase of lipopolysaccharide‐binding protein (LBP‐gut leakage marker) and eosinophils are observed. However, with local allergen challenges into the lungs, these mechanisms are further enhanced in both gut and lungs. In conclusion, the primary gut originated inflammatory responses translocates into the lungs to orchestrate AAI in a mouse model of asthma.

Unraveling the gut-Lung axis: Exploring complex mechanisms in disease interplay

“…Gut dysbiosis promotes gut inflammation and epithelial barrier damage, leading to gut including asthma and COPD [ 29 , 30 ]. The epithelial cells are arranged tightly with via junctional complexes including junctional proteins (tight, adherent and gap junctions) and desmosomes.…”

“…For example, breaching of the intestinal barrier leads to the release of various mediators that are usually impermeable into the systemic circulation. LPS, a predominant bacterial product, Zonulin, LBP and IFABP are gut specific leakage markers [ 30 ]. However, their specific role in inflammatory responses in distinct organs after leaking into the systemic circulation is not well understood.…”