Impact of fecal microbiota transplantation on TGF-ß1/Smads/ERK signaling pathway of endotoxic acute lung injury in rats.

ABSTRACT

Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Studies have shown that intestinal microbiota affect the pathology and immune function of respiratory diseases through the "gut-lung axis". The authors investigated the therapeutic effect of fecal microbiota transplantation (FMT) in rats with ALI induced by lipopolysaccharide (LPS). Rats were treated with FMT, and then measured lung wet/dry ratio, PaO2 in artery, proinflammatory marker, and TGF-ß1, Smad3, Smad7, and phosphorylated ERK (p-ERK) protein levels, as well as a histopathologic analysis and high-throughput sequencing of intestinal microbiota. FMT significantly reduced lung wet/dry ratio and TNF-α, IL-1ß, and IL-6 levels, but increased the levels of PaO2 in artery. In addition, FMT significantly decreased the expression of TGF-ß1, Smad3, and p-ERK, while increased the levels of Smad7. Lung histopathological analyses showed that FMT reduced the inflammatory cell infiltration and interstitial lung exudates. High-throughput sequencing of intestinal microbiota analyses showed that FMT reconstructed the structure of intestinal microbiota, and increased the gene abundance of the bacterial community. Therefore, FMT may act on the TGF-ß1/Smads/ERK pathway by regulating intestinal microbiota, inhibiting immune inflammation, reducing the production of inflammatory markers in the body and release, and reducing alveolar epithelial damage and repair, thereby improving the endotoxic ALI in rats induced by LPS.