Abstract
BackgroundWe hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) may ameliorate sepsis-induced acute lung injury (ALI) and change microorganism populations in the gut microbiota, such as that of Firmicutes and Bacteroidetes.MethodsA 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 h after the SC or CLP procedures. To study the role of ADMSCs during ALI caused by sepsis and examine the impact of ADMSCs on the gut microbiome composition, 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.ResultsThe 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 Escherichia–Shigella (P = 0.01) related to lipopolysaccharide production increased, and the proportion of Akkermansia (P = 0.02) related to the regulation of intestinal mucosal thickness and the maintenance of intestinal barrier function decreased. These changes in the gut microbiota break the energy balance, aggravate inflammatory reactions, reduce intestinal barrier functions, and promote the translocation of intestinal bacteria. Intervention with ADMSCs increased the proportion of beneficial bacteria, reduced the proportion of harmful bacteria, and normalized the gut microbiota.ConclusionsTherapeutically administered ADMSCs ameliorate CLP-induced ALI and improves gut microbiota, which provides a potential therapeutic mechanism for ADMSCs in the treatment of sepsis.
Highlights
Sepsis is a public health problem characterized by lifethreatening organ dysfunction due to maladjustment of the host response to infection [1, 2]
adipose-derived mesenchymal stem cells (ADMSCs) can improve the 24-h survival rate of rats, reduce lung injury, and reduce tumor necrosis factor (TNF)-α and IL-6 serum levels The cecum of cecal ligation and puncture (CLP)-induced sepsis rats was congested and necrotic, while the cecum of rats from the CLPADMSCs group was significantly improved (Fig. S1, macroscopic view of the rat model)
The results showed that the serum levels of IL-6 (P < 0.001) and TNF-α (P < 0.01) were significantly increased, and treatment with ADMSCs significantly reduced the levels of IL-6 (P < 0.01) and TNFα (P < 0.05), as shown in Fig. 1a, b
Summary
Sepsis is a public health problem characterized by lifethreatening organ dysfunction due to maladjustment of the host response to infection [1, 2]. Sepsis involves the damage of various important organ functions, including brain, kidney, and heart functions [5,6,7,8]. ALI can occur in the early stage of sepsis due to the involvement of the lungs in suppurative inflammation [9]. There are many potential pathogens that can cause sepsis [10]. There is no drug or treatment that can effectively cure sepsis [11]. It is necessary for us to develop new therapeutic methods for ALI treatment. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) may ameliorate sepsisinduced acute lung injury (ALI) and change microorganism populations in the gut microbiota, such as that of Firmicutes and Bacteroidetes
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