Luteolin ameliorates cigarette smoke-induced chronic obstructive pulmonary disease by modulating gut and lung microbiota and amino acid metabolism in C57Bl/6 mice

Exposure to cigarette smoke (CS) is a potent and major risk factor for chronic obstructive pulmonary disease (COPD). Luteolin (Lut), a flavonoid found in many edible plants, has displayed therapeutic effects on COPD; however, the underlying mechanisms are not well comprehended. In this study, C57Bl/6 J mice were exposed to CS combined with lipopolysaccharide (LPS) to induce COPD. Examination of the levels of inflammatory markers, including TNF-α, IL-1β, IL-6, IL-18, NO, and LPS, revealed that CS exposure caused significant lung injury and inflammatory reactions, while treatment with Lut (50 and 100 mg/kg/day) significantly reversed these trends. 16S rRNA sequencing showed that mice exposed to CS not only decreased the richness and composition of the lung microbiota, but also affected the gut microbiota. Lut treatment increased the richness and modulated the composition. Lut treatment altered the abundance of Pseudomonas, Streptococcus, and Actinomyces in the lung microbiota, as well as Actinobacteria, Helicobacter, and Coprococcus in the gut microbiota. Moreover, targeted metabolomics of amino acids showed seven amino acids, which were significantly altered by Lut, including serine (Ser), threonine (Thr), asparagine (Asn), glutamine (Gln), glutamic acid (Glu), histidine (His), and tyrosine (Tyr). Our study suggests that the protection effect of Lut on CS-induced COPD probably relies on the modulation of gut and lung microbiota and amino acid metabolism.