Unraveling the immunological landscape and gut microbiome in sepsis: a comprehensive approach to diagnosis and prognosis
Yali Luo, Jian Gao, Xinliang Su, Helian Li, Yingcen Li, Wenhao Qi, Xuling Han, Jingxuan Han, Yiran Zhao, Alin Zhang, Yan Zheng, Feng Qian, Hongyu He
Abstract
BACKGROUND: Comprehensive and in-depth research on the immunophenotype of septic patients remains limited, and effective biomarkers for the diagnosis and treatment of sepsis are urgently needed in clinical practice. METHODS: Blood samples from 31 septic patients in the Intensive Care Unit (ICU), 25 non-septic ICU patients, and 18 healthy controls were analyzed using flow cytometry for deep immunophenotyping. Metagenomic sequencing was performed in 41 fecal samples, including 13 septic patients, 10 non-septic ICU patients, and 18 healthy controls. Immunophenotype shifts were evaluated using differential expression sliding window analysis, and random forest models were developed for sepsis diagnosis or prognosis prediction. FINDINGS: leukocytes achieved robust outcome prediction (AUC = 0.906, 95% CI: 0.732-1.000), with further accuracy improvement when combined with clinical scores (AUC = 0.938, 95% CI: 0.796-1.000). INTERPRETATION: NK cell subsets within innate immunity exhibit significant diagnostic value for sepsis, particularly when combined with B. salyersiae and CRP. In addition, T cell phenotypes within adaptive immunity are correlated with sepsis severity and may serve as reliable prognostic markers. FUNDING: This project was supported by the National Key R&D Program of China (2023YFC2307600, 2021YFA1301000), Shanghai Municipal Science and Technology Major Project (2023SHZDZX02, 2017SHZDZX01), Shanghai Municipal Technology Standards Project (23DZ2202600).