The gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies have shown that the gut flora was significantly altered in critically ill patients. This study aimed to observe what kind of GM dysbiosis is in the early stage of sepsis and whether the application of fecal microbiota transplantation (FMT) can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. The study investigated the effect of FMT on gut microbiota, mucosal barrier function, inflammatory response, and survival in a murine model of sepsis established by cecal ligation and puncture (CLP). It is found that FMT can not only reduce morbidity and mortality and restore the abundance and diversity of the gut flora in septic mice, but can also improve the intestinal barrier function by reducing epithelial cell apoptosis, improving the composition of the mucus layer, upregulating the expression of tight junction proteins, and reducing intestinal permeability and the inflammatory response. After FMT, Lachnospiraceae contributed the most to intestinal protection through enhancement of the L-lysine fermentation pathway. FMT offers a microbe-mediated survival advantage in a murine model of sepsis. Therefore, an improved understanding of the connection between microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis.
Background and purpose To date, sepsis remains the main cause of mortality in intensive care units (ICU). This study aimed analyze the risk factors of the prognosis in sepsis patients. Methods In this case-control study, patients with sepsis admitted to the intensive care unit of a Chinese hospital between January and November 2020 were analyzed. Ultrasound and clinical data were analyzed and compared between non-survivors and survivors. The ROC curve analysis was also performed to determine the best indicator for predicting mortality. Results A total of 72 patients with sepsis in ICU were included for analysis. The basic characteristics between the survivals and non-survivals were similar, except for acute physiology and chronic health evaluation (APACHE) Ⅱ score, sepsis-related organ failure assessment (SOFA) score, lactate level, ultrasound parameters from superior mesenteric artery (SMA) such as peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI). Univariate analysis revealed that the APACHE Ⅱ score, SOFA score, lactate, low PSV, EDV, and RI were potential risk factors for mortality in sepsis, while multivariate analysis suggested that low PSV was an independent risk factor for mortality, and the adjusted odds ratio was 0.295 (95% CI: 0.094–0.925). The ROC analysis showed that the PSV (AUC = 0.99; sensitivity and specificity were 0.99 and 0.96, respectively) had good predictive value for mortality in sepsis. Conclusion Low PSV as found to be an independent risk factor and good predictor for mortality in patients with sepsis. This study shows the promise of ultrasound in predicting mortality in patients with sepsis; however, further studies are needed to validate these results.
Background This study aimed to confirm the existence of gut microbiota (GM) imbalance in the early stage of sepsis, observe the effect of fecal microbiota transplantation (FMT) on sepsis, and explore whether FMT can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. Methods The study included acute experiments and 7-day mortality observation experiments with clean-grade C57BL/6, and they were randomly divided randomly into three groups, namely, the sham group, the sepsis model group and the fecal microbiota transplantation group. Fresh feces from 10 mice were kept every day to make fecal liquid. The Sham group and the CLP group were given intragastric administration once a day with phosphate-buffered saline, and the FMT group mice were given fecal microbiota transplantation once a day. The animals were euthanized at 12, 24, and 48 h after modeling, and blood, colon, and stool from each mouse were collected at the same time.Results Colonic pathological scores, pro-inflammatory cytokines, TLR4/MyD88/NF-κB protein levels, and gene expression levels, were lower in the FMT group, while anti-inflammatory factors, mucus layer thickness, MUC2, occludin, and ZO-1 proteins were higher in the FMT group than the CLP group. Bacterial flora analysis showed gut flora was reconstructed after FMT. The species composition of the differential pathways revealed that the Lachnospiraceae group contributed the most by the L-lysine pathway of fermentation to acetate and butanoate.Conclusion GM imbalance exists early in sepsis. FMT can improve morbidity and effectively reduce mortality in septic mice. After the fecal bacteria were transplanted, the abundance and diversity of the gut flora were restored, and the microbial characteristics of the donors changed. FMT can effectively reduce epithelial cell apoptosis, improve the composition of the mucus layer, upregulate the expression of tight junction proteins, and reduce intestinal permeability and the inflammatory response, thus protecting the intestinal barrier function. After FMT, Lachnospiraceae contributes the most to intestinal protection through enhancement of the L-lysine fermentation pathway, resulting in the production of acetate and butanoate, and may be the key bacteria for short-chain fatty acid metabolism and FMT success.
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