Gut-Lung Crosstalk in Sepsis-Induced Acute Lung Injury

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common acute and severe cases of the respiratory system with complicated pathogenesis and high mortality. Sepsis is the leading indirect cause of ALI/ARDS in the intensive care unit (ICU). The pathogenesis of septic ALI/ARDS is complex and multifactorial. In the development of sepsis, the disruption of the intestinal barrier function, the alteration of gut microbiota, and the translocation of the intestinal microbiome can lead to systemic and local inflammatory responses, which further alter the immune homeostasis in the systemic environment. Disruption of homeostasis may promote and propagate septic ALI/ARDS. In turn, when ALI occurs, elevated levels of inflammatory cytokines and the shift of the lung microbiome may lead to the dysregulation of the intestinal microbiome and the disruption of the intestinal mucosal barrier. Thus, the interaction between the lung and the gut can initiate and potentiate sepsis-induced ALI/ARDS. The gut-lung crosstalk may be a promising potential target for intervention. This article reviews the underlying mechanism of gut-lung crosstalk in septic ALI/ARDS.

Keywords: acute lung injury; gut microbiome; gut-lung crosstalk; inflammation; sepsis.

FIGURE 1

Effect of increased inflammatory cytokines and lung microbiome alteration on the gut in septic ALI/ARDS.

FIGURE 2

Intestinal barrier disruption by increased cytokines during sepsis. Tight junctions between cells play a critical role in gut barrier function. In sepsis, tight junctions are destructed by inflammatory cytokines production.

FIGURE 3

Effect of sepsis-related intestinal failure on the lung. Bacterial dysbiosis can activate local intestinal inflammatory responses, producing DAMPs, which enter the systemic circulation through mesenteric lymphatic vessels. Immune cells recognize DAMPs and secreting pro-inflammatory factors that promote lung injury. DAMPs: danger-associated molecular patterns.