Characterization of the Blood and Neutrophil-specific Microbiomes and Exploration of Potential Bacterial Biomarkers for Sepsis in Surgical Patients

Introduction: Recent studies have demonstrated the presence of a circulating microbiome in the blood of healthy subjects and chronic inflammatory patients. However, our knowledge regarding the blood microbiome and its potential roles in surgical patients remains very limited. The objective of this study was to determine the blood microbial landscape in surgical patients and to explore its potential associations with postoperative sepsis.

Materials And Methods: 2825 patients who underwent surgical treatments were screened for enrollment and 204 cases were recruited in this study. The patients were sub-grouped into noninfected, infected, sepsis, and septic shock according to postoperative clinical manifestations. A total of 222 blood samples were obtained for neutrophil isolation, DNA extraction and high-throughput sequencing, quantitative proteomics analysis, and flow cytometric analyses.

Results: Blood and neutrophils in surgical patients and healthy controls contained highly diverse microbiomes, mainly comprising Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. The majority (80.7%-91.5%) of the microbiomes were composed of gut-associated bacteria. The microbiomes in septic patients were significantly distinct from those of healthy controls, and marked differences in microbiome composition were observed between sepsis and septic shock groups. Several specific bacterial genera, including Flavobacterium, Agrococcus, Polynucleobacter, and Acidovorax, could distinguish patients with septic shock from those with sepsis, with higher area under curve values. Moreover, Agrococcus, Polynucleobacter, and Acidovorax were positively associated with the sequential (sepsis-related) organ failure assessment scores and/or acute physiology and chronic health examination scores in septic shock patients. The proteins involved in bactericidal activities of neutrophils were downregulated in septic patients.

Conclusions: We present evidence identifying significant changes of blood and neutrophil-specific microbiomes across various stages of sepsis, which might be associated with the progression of sepsis after surgical treatments. Several certain bacterial genera in blood microbiome could have potential as microbial markers for early detection of sepsis.