Metformin in SALI

The gut microbiota imbalance is primarily characterized by an increase in the abundance of succinate-producing bacteria (Prevotellaceae and Bacteroidaceae) and a decrease in succinate-consuming bacteria (Ruminococcaceae and Clostridiaceae) after CLP-induced SALI. This dysbiosis leads to elevated succinate levels in both serum and lung tissue. However, metformin effectively reduces succinate levels by modulating the gut microbiota, which subsequently regulates the polarization of alveolar macrophages (AMs) and exerts anti-inflammatory effects by inhibiting succinate receptor 1 (SUCNR1) and the downstream PI3K/AKT/HIF-1α signaling pathway.