Myeloid Bias in the Bone Marrow of Septic Patients and Its Correlation With Disease Severity and Prognosis: A Single-Center, Prospective Cohort Study

Registry record from ClinicalTrials.gov (NCT07667153). This is a study registration, not published results. Lead sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Recruitment status: NOT_YET_RECRUITING. Study type: OBSERVATIONAL. Enrollment: 45 participants (ESTIMATED). Conditions: Sepsis, Septic Shock. Interventions: PROCEDURE: Bone marrow aspirate collection. Primary outcome measures: Percentage and Absolute Count of Hematopoietic Stem Cells (HSCs) in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3); Percentage and Absolute Count of Common Myeloid Progenitors (CMPs) in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3); Percentage and Absolute Count of Granulocyte-Monocyte Progenitors (GMPs) in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3); Percentage and Absolute Count of Megakaryocyte-Erythroid Progenitors (MEPs) in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3); Percentage and Absolute Count of Common Lymphoid Progenitors (CLPs) in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3); GMP-to-CLP Ratio and Absolute Differential Count Index in Bone Marrow (Primary Composite Index) , Between 48 and 72 hours after enrollment (preferably day 3); Percentage and Absolute Count of PMN-MDSCs in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3); Percentage and Absolute Count of M-MDSCs in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3); PD-L1 Expression Level and PD-L1⁺ Absolute Count on Bone Marrow MDSCs , Between 48 and 72 hours after enrollment (preferably day 3); Percentage and Absolute Count of T Cells in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3); Percentage and Absolute Count of NK Cells in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3); Percentage and Absolute Count of Monocytes in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3); Percentage and Absolute Count of Neutrophils in Bone Marrow , Between 48 and 72 hours after enrollment (preferably day 3). Brief summary: Sepsis remains a leading cause of critical illness worldwide, yet the underlying mechanisms driving its profound and persistent immune dysfunction are incompletely understood. The bone marrow, as the birthplace of all immune cells, plays a central role in orchestrating systemic immune responses. Emerging evidence from animal models suggests that sepsis triggers emergency myeloid-biased hematopoiesis in the bone marrow, characterized by expansion of myeloid progenitors and myeloid-derived suppressor cells (MDSCs) at the expense of lymphoid and erythroid lineages. This bone marrow remodeling precedes peripheral immune alterations and may represent the initiating event of sepsis-induced immunosuppression. However, direct clinical evidence in humans is scarce. This prospective, single-center cohort study aims to systematically characterize bone marrow hematopoietic remodeling in patients with septic shock, compared to critically ill non-septic patients and healthy volunteers, and to determine whether the degree of myeloid lineage bias correlates with disease severity, immunosuppression, and adverse clinical outcomes. This study will enroll three cohorts. Bone marrow aspirates and peripheral blood samples will be collected at 48-72 hours post-enrollment for flow cytometric immunophenotyping of hematopoietic stem/progenitor cells, MDSC subsets, and PD-L1 expression, as well as cytokine profiling and exploratory single-cell transcriptomics. Rectal swabs will be collected synchronously for 16S rRNA sequencing and untargeted metabolomics to investigate the association between gut microbiota, microbial metabolites, and bone marrow myeloid skewing, testing the gut-bone marrow-immune axis hypothesis. Clinical severity (SOFA/APACHE II), secondary infections, and 90-day mortality will be assessed to evaluate prognostic value. By integrating bone marrow hematopoiesis, gut microbiome, and clinical outcomes, this study seeks to provide novel mechanistic insights into sepsis-induced immunoparalysis and identify potential biomarkers or therapeutic targets for immune restoration.