Multi-Omics Analysis Identifies Gut-Associated Metabolic Signatures Associated with Metformin-Mediated Protection Against LPS-Induced Lung Injury

Background/Objectives: Lipopolysaccharide (LPS)-induced lung injury involves pulmonary inflammation, metabolic disturbance, and intestinal dysregulation. This study investigated whether metformin attenuates LPS-induced lung and colonic injury and characterized associated gut microbiota-metabolite changes.

Methods

Male C57BL/6J mice were assigned to control (CON), LPS, metformin 200 mg/kg (MET 200 mg/kg), and metformin 400 mg/kg (MET 400 mg/kg) groups. Metformin was administered by gavage for 7 days before intranasal LPS challenge. Lung and colon injury were assessed by histology, immunostaining, ELISA, and RT-qPCR. Untargeted serum metabolomics, colonic-content metabolomics, and colonic-content shotgun metagenomics were performed in the CON, LPS, and MET 400 mg/kg groups. Differential-feature, pathway-enrichment, and exploratory Spearman correlation analyses were conducted.