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.

针对盲肠结扎穿刺（CLP）诱导的脓毒症相关性急性肺损伤（SALI）模型的研究显示，该模型的肠道菌群失调主要表现为产琥珀酸菌（普雷沃氏菌科, Prevotellaceae；拟杆菌科, Bacteroidaceae）丰度升高，而耗琥珀酸菌（瘤胃球菌科, Ruminococcaceae；梭菌科, Clostridiaceae）丰度降低。此类菌群失调可导致血清与肺组织内的琥珀酸水平升高。二甲双胍可通过调控肠道菌群有效降低琥珀酸水平，继而调节肺泡巨噬细胞（alveolar macrophages, AMs）的极化状态，并通过抑制琥珀酸受体1（SUCNR1）及其下游PI3K/AKT/HIF-1α信号通路发挥抗炎作用。