Longitudinal Multi-omic Phenotyping Reveals Host-microbe Responses to Bariatric Surgery, Glycaemic Control and Obesity

Abstract Resolution of type-2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB). However, the underlying mechanisms have not been fully elucidated. To address this we compared the integrated serum, urine and faecal metabolic profiles of obese participants with and without T2D (n=81, T2D=42) with participants who underwent RYGB or sleeve gastrectomy (pre and 3-months post-surgery; n=27), taking diet into account. We co-modelled these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level. Bariatric surgery reversed a number of disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlapped with both diabetes (19.3% commonality) and BMI (18.6% commonality). However, the percentage overlap between diabetes and BMI was minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota was more strongly correlated to BMI than T2D, although we identified some pathways such as amino acid metabolism that correlated with changes to the gut microbiota and which influence glycaemic control. Improved understanding of GM-host co-metabolism may lead to novel therapies for weight-loss or diabetes.