<strong>Gut microbiota-derived autoinducer-2 regulates lung inflammation through the gut-lung axis</strong>

Abstract Objective: This study aimed to determine whether autoinducer-2 (AI-2), a crucial bacterial metabolite and quorum sensing molecule, is involved in lung immunity through the gut-lung axis. Methods: The level of AI-2 and the gut microbiome composition were analysed in the stools from pneumonic patients and the mouse model of acute lung injury. The effect of AI-2 on lung inflammation was further investigated in the mouse model. Results: The diversity of the faecal microbiota was reduced in pneumonic patients treated with antibiotics compared with healthy volunteers. The AI-2 level in the stool was positively correlated with inflammatory molecules in the serum of pneumonic patients. Intraperitoneal injection of AI-2 reinforced lung inflammation in the acute lung injury mouse model, characterized by increased secretion of inflammatory molecules, including IL-6, IL-1β, C-C chemokines, and CXCL chemokines, which were alleviated by the AI-2 inhibitor D-ribose. Conclusions: Our results suggested that gut microbiota-derived AI-2 could modulate lung inflammation through the gut-lung axis. Keywords: lung immunity; gut microbiota; autoinducer-2; gut-lung axis; quorum sensing.