Sleeve gastrectomy promotes colitis-associated colorectal cancer in a murine model via a modified gut microbiome

Abstract

Colorectal cancer (CRC) remains the third leading cause of cancer death in the United States with an alarming rise among young (<50-years-old) patients.1 Epidemiologically, obesity appears to be a risk factor for CRC.1 Although bariatric surgery has been shown to be associated with decreased risk for most cancers, studies to date on bariatric surgery and CRC continue to yield conflicting results.2 One possible explanation for this seeming irreconcilability is the inherent heterogeneity of CRC with its varied mechanisms. This is likely compounded by the differing bariatric operations currently employed. Here, we sharpen our focus and investigate how the most performed bariatric operation, sleeve gastrectomy (SG), affects colitis-associated CRC. Using a murine model, we found that SG significantly exacerbates both colitis and colitis-associated CRC. Using a germ-free (GF) microbiota transplant model, we found that the post-SG microbiota, when transplanted into GF mice, is capable of independently recapitulating the tumor-promoting phenotype of SG. Our results suggest that the postsurgical microbiome plays a key causal role in the increased risk for CRC after SG. This finding represents the first step in our understanding of this complex relationship that is at the intersection of two rising public health threats.