Microbiota–Gut–Lung Axis Involvement With Lung Protection of <i>Houttuynia cordata</i> Thunb. Essential Oil In Vivo, Confirmed by 16S rRNA Sequencing Combined With UPLC‐Q‐TOF/MS‐Based Serum Metabolomics

The lung and gut were a pair of related organ systems, and the study aimed to investigate the lung protection of Houttuynia cordata Thunb. essential oil (HEO) on gut-lung crosstalk in lipopolysaccharide-induced acute lung injury (ALI) rats. Animal results showed that HEO performed lung protection by alleviating lung histopathological changes. Moreover, gut-lung interaction was shown during HEO-exerted lung protection, evidenced by overlap between lung and gut on correcting inflammatory profile through suppressing serum IL-1β and TLR4/NF-κB p65 signaling, suggesting that the intestine could behave as a "social" capacity to protect distal lung via gut-lung interaction. Furthermore, HEO was demonstrated to strengthen the intestinal barrier by elevating Zonula occludens-1 and inhibiting NLRP3 inflammasome through interfering with mitochondria-endoplasmic reticulum contacts through decreasing mitofusin 2, and its intestinal protection was also confirmed in cell experiments. Subsequently, 16S rRNA sequencing revealed that HEO significantly restored gut microbiota dysbiosis and increased short-chain fatty acids, which was in parallel with attenuation of metabolic abnormalities via UPLC-Q-TOF/MS-based serum metabolomics. Metabolomic analysis suggested that tryptophan metabolism was identified to be one of the critical pathways in gut-lung communication, which could be traced to Bacteroides and Lactobacillus in ALI rats exposed to HEO, concluding that lung protection of HEO could be driven by microbiota-gut-lung axis.