Gastric dilation following vertical sleeve gastrectomy reflects adaptive stem cell-driven regeneration without association with weight regain or increased cancer risk

Aims: Bariatric surgery is the most effective intervention for sustained weight loss and the improvement of obesity-related comorbidities. Among these procedures, vertical sleeve gastrectomy (VSG) is the most commonly performed worldwide. Yet, post-VSG gastric dilation has been hypothesized to contribute to failure in weight loss or even weight regain by increasing the secretion of ghrelin, an orexigenic hormone primarily produced in the stomach. However, the relationship between gastric dilation, its underlying mechanism, and its clinical implications remain unclear. Materials and methods: To investigate this, we utilized both a mouse model of VSG and corpus epithelial samples from patients who had undergone VSG. Key findings: Using a diet-induced obese mouse model, we found that VSG leads to significant gastric remodeling, yet neither stomach expansion nor increased ghrelin secretion correlated with weight regain. Single-cell RNA sequencing of corpus epithelial cells from VSG patients further revealed an associated with epithelial regeneration, marked by gastric stem cell expansion and upregulation of repair-associated genes. RNA sequencing also showed enhanced stem cell activity alongside upregulation of tumor suppressor genes and long non-coding RNAs, suggesting a potential protective mechanism against gastric cancer despite rapid cellular proliferation. Significance: These findings challenge the assumption that gastric dilation is a predictor of poor surgical outcomes and instead suggest that it is an adaptive response to VSG, offering new insights into post-VSG gastric remodeling.