Methods in Bariatric Surgery & Microbiome in Cancer Outcomes

Arvind Vignesh Ramesh¹Sydney Clarice Joseph¹Margaret Sue Bohm¹Boston William Simmons¹Brianne Marie Hibl²Oluwatosin Tolulope Asunloye¹Ki-Suk Kim¹Teri D. Stevenson³David H. Wasserman³Joseph Francis Pierre⁴Liza Makowski^1*Laura Marie Sipe^5*

• ¹University of Tennessee Health Science Center (UTHSC), Memphis, United States
• ²The University of Utah, Salt Lake City, Utah, United States
• ³Vanderbilt Mouse Metabolic Phenotyping Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States
• ⁴University of Wisconsin-Madison, Madison, Wisconsin, United States
• ⁵University of Mary Washington, Fredericksburg, Virginia, United States

Obesity is a global epidemic that has affected the lives of over 14% of adults worldwide and over a third of Americans. Obesity is associated with the increased risk of thirteen obesity-associated cancers and poor cancer outcomes. Bariatric surgery is the most effective method of sustained weight loss and has been steadily increasing in clinical use over the past 4 decades. Importantly, bariatric surgery is established to decrease cancer risk. Vertical sleeve gastrectomy (VSG) is currently the most common bariatric surgery procedure. To evaluate underlying mechanisms of bariatric associated cancer protection, we developed a robust pre-clinical model of bariatric surgery-induced weight loss in mice. Using multiple strains, we established detailed procedures, defined best practices, and noted specific controls to include to examine mediators critical to cancer onset. This VSG protocol includes stringent pre-and post-operational measures to reduce stress-associated weight loss in obese mice to achieve rigorous and reproducible bariatric surgeryassociated weight loss. In addition, we describe collection of fecal and intestinal samples as well as Peyer's patches as important mediators of bariatric surgery's impact on cancer risk. In conclusion, as obesity and weight loss approaches including bariatric surgery are increasingly examined in cancer risk and outcomes including immunotherapy, the establishment of robust pre-clinical interventions will allow the field to address critical underlying mechanisms mediating the benefits of weight loss and cancer.New and Noteworthy: Obesity increases cancer risk and leads to poor outcomes and survival. Bariatric surgery is an effective method of sustained weight loss. To best model obesity, weight loss, and impacts on cancer risk or outcomes, we developed a robust pre-clinical model of bariatric surgery in mice. Because bariatric surgery leads to sustained impacts on the gut microbiome, which can inform anti-tumor immunity, this protocol provides rigorous methods for the collection of intestinal microbiota and Peyer's patches.