Assessing the impact of gut microbiota and metabolic products on acute lung injury following intestinal ischemia-reperfusion injury: harmful or helpful?

Abstract

Ischemia-reperfusion injury (IRI) is a common and clinically significant form of tissue damage encountered in medical practice. This pathological process has been thoroughly investigated across a variety of clinical settings, including, but not limited to, sepsis, organ transplantation, shock, myocardial infarction, cerebral ischemia, and stroke. Intestinal IRI, in particular, is increasingly recognized as a significant clinical entity due to marked changes in the gut microbiota and their metabolic products, often described as the body's "second genome." These changes in intestinal IRI lead to profound alterations in the gut microbiota and their metabolic outputs, impacting not only the pathology of intestinal IRI itself but also influencing the function of other organs through various mechanisms. Notable among these are brain, liver, and kidney injuries, with acute lung injury being especially significant. This review seeks to explore in depth the roles and mechanisms of the gut microbiota and their metabolic products in the progression of acute lung injury initiated by intestinal IRI, aiming to provide a theoretical basis and directions for future research into the treatment of related conditions.

Keywords: acute lung injury; gut; intestinal ischemia-reperfusion injury; ischemia-reperfusion injury; microbiota.

Figure 1

Schematic representation of the pathophysiological mechanisms leading to ALI following intestinal IRI. Post-intestinal IRI, there are pronounced alterations in both the gut microbiota and their metabolic outputs, which contribute to multi-organ dysfunction. A key identified pathway involves a disruption of the equilibrium between the intestinal bacterial populations that produce and consume succinate. This disruption leads to an aberrant accumulation of succinate in the lungs, which fosters the polarization of alveolar macrophages and expedites the apoptosis of alveolar epithelial cells, thereby intensifying pulmonary injury. Moreover, investigation revealed that prophylactic administration of Bifidobacterium bifidum PRL2010 significantly attenuated pulmonary neutrophil infiltration and mitigated bacterial translocation in the context of intestinal IRI-induced ALI.