Butyrate and Propionate Restore the Cytokine and House Dust Mite Compromised Barrier Function of Human Bronchial Airway Epithelial Cells

Abstract

Barrier dysfunction of airway epithelium contributes to the development of allergies, airway hyper-responsiveness and immunological respiratory diseases. Short-chain fatty acids (SCFA) enhance and restore the barrier function of the intestinal epithelium. This study investigated whether acetate, propionate and butyrate enhance the integrity of bronchial epithelial cells. Differentiating human bronchial epithelial cells (16HBE) grown on transwells were exposed to butyrate, propionate and acetate while trans-epithelial electrical resistance was monitored over time. Restorative effects of SCFA were investigated by subsequent incubation of cells with IL-4, IL-13 or house dust mite extract and SCFA. SCFA effects on IL-4-induced cytokine production and the expression of zonula occludens-1 (ZO-1) and Mitogen-activated protein kinases (MAPK) signalling pathways were investigated by ELISA and Western blot assays. Propionate and butyrate enhanced the barrier function of differentiating 16HBE cells and induced complete recovery of the barrier function after exposure to the above-mentioned stimuli. Butyrate decreased IL-4-induced IL-6 production. IL-4 decreased ZO-1 protein expression and induced phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in 16HBE cells, both of which could be restored by SCFA. SCFA showed prophylactic and restorative effects on airway epithelial barrier function, which might be induced by increased ZO-1 expression.

Leaky Gut: Effect of Dietary Fiber and Fats on Microbiome and Intestinal Barrier

“…Butyrate suppresses cytokine-induced barrier dysfunction by modifying claudin-2 levels in vitro [ 65 ]. Animal studies have also shown similar protective effects on not only the intestinal barrier [ 66 , 67 ] but also the airway epithelial barrier [ 68 ]. Fecal calprotectin, a marker of intestinal inflammation, is diminished by administration of butyrate to UC patients [ 69 ].…”

Anti-Inflammatory Function of Fatty Acids and Involvement of Their Metabolites in the Resolution of Inflammation in Chronic Obstructive Pulmonary Disease

“…Interestingly, both butyrate and propionate restored and even improved the barrier function of the damaged airway epithelium, which may be mediated by increased expression of zonula occludens-1 (ZO-1) tight junction proteins [ 235 ]. Airway epithelial barrier dysfunction and dense contact disruption have been reported in asthma and in smoking and COPD [ 236 , 237 ].…”

“…Airway epithelial barrier dysfunction and dense contact disruption have been reported in asthma and in smoking and COPD [ 236 , 237 ]. In this regard, restoration of barrier function under the influence of SCFAs may have some clinical significance [ 235 ].…”

Investigation of Pharmacological Mechanisms of Schisandrin a for the Treatment of Asthma Determined by Network Pharmacology and Experimental Validation

“…On the other hand, the phosphorylation of NF-κB can increase the expression of iNOS and COX-2 [8,9]. Most of the current clinical treatments for asthma use western medicine treatments, such as corticosteroids and β2 receptor agonists, but not all patients respond and larger doses of corticosteroids cause many side effects [10,11]. In recent years, traditional Chinese medicine (TCM) has been increasingly selected to treat asthma.…”