Early Changes in Immune Cell Count, Metabolism, and Function Following Sleeve Gastrectomy: A Prospective Human Study.

OBJECTIVE:To characterize longitudinal changes in blood biomarkers, leukocyte composition, and gene expression following laparoscopic sleeve gastrectomy (LSG). BACKGROUND:LSG is an effective treatment for obesity, leading to sustainable weight loss and improvements in obesity-related comorbidities and inflammatory profiles. However, the effects of LSG on immune function and metabolism remain uncertain. METHODS:Prospective data were collected from 23 enrolled human subjects from a single institution. Parameters of weight, comorbidities, and trends in blood biomarkers and leukocyte subsets were observed from preoperative baseline to 1 year postsurgery in 3-month follow-up intervals. RNA sequencing was performed on pairs of whole blood samples from the first 6 subjects of the study (baseline and 3 months postsurgery) to identify genome-wide gene expression changes associated with undergoing LSG. RESULTS:LSG led to a significant decrease in mean total body weight loss (18.1%) at 3 months and among diabetic subjects a reduction in hemoglobin A1c. Improvements in clinical inflammatory and hormonal biomarkers were demonstrated as early as 3 months after LSG. A reduction in neutrophil-lymphocyte ratio was observed, driven by a reduction in absolute neutrophil counts. Gene set enrichment analyses of differential whole blood gene expression demonstrated that after 3 months LSG induced transcriptomic changes not only in inflammatory cytokine pathways but also in several key metabolic pathways related to energy metabolism. CONCLUSIONS:LSG induces significant changes in the composition and metabolism of immune cells as early as 3 months postoperatively. Further evaluation is required of bariatric surgery's effects on immunometabolism and the consequences for host defense and metabolic disease.