Untargeted metabolomics study of urine in patients with acute lung injury due to abdominal sepsis
XUE Hai-ling,ZHANG Ai-min,GE Li-xiu
Abstract:
Objective To identify specific metabolic markers and pathways for sepsis with acute lung injury (ALI) using untargeted metabolomics, providing new insights for clinical diagnosis and treatment. Methods A total of 33 sepsis patients admitted to our hospital from July 2022 to October 2023 were enrolled and divided into sepsis with ALI group (22 cases) and sepsis without ALI group (11 cases). Fifteen healthy adults were selected as the control group. Urine samples from all three groups were analyzed by ultra-high performance liquid chromatography-mass spectrometry for metabolomic profiling, and differential metabolites and metabolic pathways were statistically analyzed. Results A total of 456 metabolites were identified in 48 participants. Among them, 312 metabolites could distinguish sepsis patients from healthy controls, and 109 metabolites could distinguish the sepsis with ALI group from the sepsis without ALI group. Compared with the sepsis without ALI group, the metabolites increased in the sepsis with ALI group were mainly involved in energy metabolism, inflammation and immune activation, lipid metabolism disorders and cell membrane damage, oxidative stress and detoxification responses, and organ dysfunction with reduced clearance. The metabolites decreased in the sepsis with ALI group were mainly associated with the antioxidant defense system, impaired energy metabolism and mitochondrial function, reduced hepatic synthesis and detoxification, consumption or reduced synthesis of protective/signaling lipid mediators, and amino acid metabolism. A total of 22 metabolic pathways were significantly altered, mainly including disturbances in the citrate cycle (TCA cycle), β-alanine metabolism, and phenylalanine metabolism. Conclusion Using untargeted metabolomics, we identified significantly altered metabolites in the urine of sepsis patients with ALI. These patients exhibited disturbances in metabolic pathways such as the citrate cycle, β-alanine metabolism, and phenylalanine metabolism. These metabolites and pathways may serve as specific diagnostic markers for sepsis with ALI.
