Abstract
BACKGROUND: The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application. METHOD: In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out. Finally, the above results were validated by the microbiome and transcriptomics analysis in an animal model of sepsis. RESULTS: Patients with sepsis showed destruction of symbiotic flora and elevated abundance of Enterococcus, which were validated in animal experiments. Additionally, patients with a high burden of Bacteroides, especially B. vulgatus, had higher Acute Physiology and Chronic Health Evaluation II scores and longer stays in the intensive care unit. The intestinal transcriptome in CLP rats illustrated that Enterococcus and Bacteroides had divergent profiles of correlation with differentially expressed genes, indicating distinctly different roles for these bacteria in sepsis. Furthermore, patients with sepsis exhibited disturbances in gut amino acid metabolism compared with healthy controls; namely, tryptophan metabolism was tightly related to an altered microbiota and the severity of sepsis. CONCLUSION: Alterations in microbial and metabolic features in the gut corresponded with the progression of sepsis. Our findings may help to predict the clinical outcome of patients in the early stage of sepsis and provide a translational basis for exploring new therapies.