Oral Multi-Enzymatic Manganese–Carbon Dots Alleviate Sepsis-Associated Lung Injury via the Gut–Lung Axis

, concomitant with elevated indole-3-propionic acid (IPA) production. Subsequent in vitro studies demonstrate that IPA likely binds primarily to the aryl hydrocarbon receptor (AHR), promoting both efferocytosis and anti-inflammatory polarization in macrophages, thereby mitigating septic lung injury. Notably, the fecal microbiota transplantation (FMT) from Mn-CDs-treated mice not only alleviated systemic symptoms but also effectively promoted efferocytic polarization of pulmonary macrophages in septic mice. Depletion of the gut microbiota resulted in a significant loss of the protective efficacy of Mn-CDs in a murine model of septic lung injury. Collectively, the gut-lung axis mediated by microbiota-derived IPA and macrophage efferocytosis contributes to the remediation of septic lung injury, highlighting the potential of Mn-CDs in microbiome-directed critical care.