Adipose-Derived Mesenchymal Stem Cells Attenuate Acute Lung Injury Through Regulation of the Gut Microbiota in Septic Rats

Abstract

Background We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) may ameliorate sepsis-induced acute lung injury (ALI) by increasing or decreasing microorganism populations in the gut microbiota, such as that of Firmicutes and Bacteroidetes. Methods A total of 60 male adult Sprague-Dawley (SD) rats were separated into three groups: the sham control (SC) group, the sepsis induced by cecal ligation and puncture (CLP) group, and the ADMSC treatment (CLP-ADMSCs) group, in which rats underwent the CLP procedure and then received 1 × 106 ADMSCs. Rats were sacrificed 24 hours after the SC or CLP procedures. To investigate the relationship between sepsis-induced ALI and the gut microbiota, rat lungs were histologically evaluated using hematoxylin and eosin (H&E) staining, serum levels of pro-inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA), and fecal samples were collected and analyzed using 16S rDNA sequencing. Results The serum levels of inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6, were significantly increased in rats after the CLP procedure, but were significantly decreased in rats treated with ADMSCs. Histological evaluation of the rat lungs yielded results consistent with the changes in IL-6 levels among all groups. Treatment with ADMSCs significantly increased the diversity of the gut microbiota in rats with sepsis. The principal coordinates analysis (PCoA) results showed that there was a significant difference between the gut microbiota of the CLP-ADMSCs group and that of the CLP group. In rats with sepsis, the proportion of Bacteroides related to energy consumption and Escherichia–Shigella related to lipopolysaccharide production increased, and the proportion of Akkermansia related to the regulation of intestinal mucosal thickness and the maintenance of intestinal barrier function decreased. Furthermore, the proportion of Firmicutes related to energy storage, such as Verrucomicrobia, decreased. Intervention with ADMSCs increased the proportion of beneficial bacteria, reduced the proportion of harmful bacteria, and normalized the gut microbiota, thus, improving the sepsis-induced ALI. Conclusions Therapeutically administered ADMSCs may improve CLP-induced ALI by regulating the gut microbiota, providing a potential mechanism by which mesenchymal stem cells treat sepsis.