Gut microbiota-derived indole-3-propionic acid protects the airway barrier through activating AhR/IL-22 signaling in cigarette smoke-induced chronic obstructive pulmonary disease
Translational study reveals gut-derived indole-3-propionic acid protects the airway barrier in chronic obstructive pulmonary disease, highlighting a therapeutic role for the gut-lung axis.
Key Points
To determine how gut microbiota dysbiosis and specific bacterial metabolites influence airway barrier integrity via the gut-lung axis in cigarette smoke-induced chronic obstructive pulmonary disease.
Exposed mice and human bronchial epithelial (pNHBE) cells to cigarette smoke, analyzing microbial and metabolic profiles via 16S rRNA sequencing and untargeted metabolomics.
Performed fecal microbiota transplantation, indole-3-propionic acid (IPA) administration, and AAV-mediated knockdown (AAV-shAhR) or overexpression (AAV-AhR) of the aryl hydrocarbon receptor in mice.
Assessed correlations between plasma IPA concentrations, AhR expression, and lung function (FEV1% predicted) in human patients with chronic obstructive pulmonary disease.
Cigarette smoke exposure induced gut dysbiosis with reduced Allobaculum, Bifidobacterium, and Akkermansia, depleted tryptophan metabolism and IPA, and disrupted tight junction proteins ZO-1 and occludin.
IPA treatment restored ZO-1 and occludin expression, elevated IL-22, reduced inflammatory cytokines IL-6 and IL-1β, and improved lung function, whereas AhR knockdown abolished these protective effects.
In patients with COPD, reduced circulating IPA positively correlated with AhR expression (r = 0.6401, P < 0.05) and lung function measured by FEV1% predicted (r = 0.5536, P < 0.05).