Swiss Multicenter Randomized Controlled Trial on different Limb Lengths in Gastric Bypass Surgery (SLIM)

Background: Obesity and diabetes are reaching epidemic proportions. In patients with morbid obesity, only bariatric operations lead to sustained weight loss and relief of co-morbidities in the majority of patients. Laparoscopic Roux-Y-gastric bypass (RYGB) is one of the most frequently performed bariatric operations, but it is still unknown why some patients respond much better than others. Therefore, a number of variations of this operation have been introduced. The total small bowel length differs by many meters between individuals, and the proportions of the three bowel segments involved in RYGB (Fig. 1) are likely to influence the success. Increasing the length of small bowel being bypassed has the potential to improve the effectiveness of the operation, but carries the risk of nutrient deficiencies. The exact mechanisms of surgically induced remission of metabolic syndrome are not yet fully understood.Overall Objectives: A longer bypassed, biliopancreatic limb (BPL) has the potential to be more effective compared to the standard RYGB. By measuring the total bowel length, the best length of the bypassed BPL in relation to the other two bowel segments (AL: alimentary limb; CL: common limb) will be determined in each individual patient for an optimal result in terms of metabolic outcomes with minimal side effects. To better understand the clinical outcomes, we also will address the mechanistic underpinnings of weight loss surgeries focusing on the crosstalk between enteroendocrine cells – intestinal immune cells – gut microbiota/ metabolites.Specific Aims/Methods: In this double-blinded, randomized controlled trial at 16 Swiss, one high volume Brazilian, and one Finnish bariatric reference centers, we hypothesize that a longer BPL leads to better weight loss (and remission of co-morbidities, superiority) without increasing the rate of nutrient deficiency (non-inferiority). We compare two groups (a long BPL of 180cm / AL of 80cm with a short BPL of 80cm / AL of 180cm). The total bowel length measurement will additionally allow us to study the effect of the CL on the metabolic outcome. A mechanistic substudy will assess the crosstalk of enteroendocrine cells – intestinal immune cells – gut microbiota/ metabolites, and how their interaction translates into systemic metabolic effects (i.e. glucose homeostasis and metabolomic signatures).Expected Results: The outcome of RYGB can be improved with a longer BPL: either with a BPL-length of 180cm in all patients or with the length tailored according to the total bowel length of each individual patient. On a mechanistic level, we expect that the metabolic outcome is mediated by changes in intestinal homeostasis that may involve enteroendocrine cells – intestinal immune cells – gut microbiota/ metabolites and/or their interaction.Impact: Improving the results of RYGB will have a major impact on the multimodal treatment options of morbid obesity and diabetes as chronic diseases. A better understanding of bariatric surgery mechanisms will help find potential targets for pharmacological treatment strategies of the pandemic of obesity and diabetes.