Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-kB signaling pathway

Abstract

Acute lung injury (ALI) is a common acute respiratory disease treated in the clinic. Intestinal microflora disorder affect lung diseases through the gut-lung axis. In this study, we explored the regulatory mechanism of the gut flora in the host defense against lipopolysaccharide (LPS)-induced ALI through the TLR4/NF-kB pathway by constructing a gut microflora dysbiosis-model with antibiotic administration and reconstruction of the intestinal microecology. Then, high-throughput sequencing was performed, and the levels of secreted IgA (sIgA), β-defensins, and Muc2 were measured to assess the gut flora and mucosal barrier. The expression of TLR4, NF-kB, TNF-α, IL-1β, oxidative stress and the lung wet/dry (W/D) ratio were evaluated to assess lung damage. Hematoxylin and eosin (HE) staining was performed to evaluate the damage to the gut and lung tissues. Accordingly, gut microbiota imbalance may regulate the TLR4/NF-kB signaling pathway in the lung immune system, activating oxidative stress in the lung and mediating lung injury through the regulation of the gut barrier. However, fecal microbiota transplantation (FMT) impairs the activity of the TLR4/NF-kB signaling pathway in the lung and decreases oxidative stress in animals with ALI by restoring the gut microecology. CONCLUSIONS: Our results indicated the protective effect of gut flora in regulating immunity of LPS-induced ALI by modulating the TLR4/NF-kB signaling pathway which may induce inflammation and oxidative stress.

Keywords: Acute lung injury (ALI); Intestinal microbiota; Lipopolysaccharide (LPS); NF-kB; TLR4.