Altered intestinal microbiome and metabolome correspond to the
clinical outcome of sepsis
by Silei Sun,
Daosheng Wang, Danfeng Dong, Lili Xu, Mengqi Xie, Yihui Wang, Tongtian Ni,
Weisong Jiang, Xiaojuan Zhu, Ning Ning, Qian Sun, Shuyuan Zhao, Mengjiao Li,
Peili Chen, Meiling Yu, Jian Li.
Critical Care volume 27,
Article number: 127 (2023) Published: 28
March 2023
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.
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