Bariatric Surgery: Microbiome & Diabetes

This study is a prospective cohort study, following 80 morbidly obese patients undergoing bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB). The investigators are measuring intestinal microbiota (IM) and oral microbiota (OM) at the beginning before any treatment, at the time of surgery, which is after a very low calorie standard diet, and 1 and 6 months after surgery. The investigators assess whether changes in IM are related to changes in insulin resistance (IR), other features of the metabolic syndrome (MetS) and OM.

Morbid obesity is associated with not only type 2 diabetes (T2D) of morbidly obese patients), but also cardiovascular complications, all of which remarkably improved and even resolved with bariatric surgery, of which the RYGB surgery has become the gold standard. Many studies have shown that within a few weeks post-RYGB there is dramatic improvement in IR and/or T2D independent of weight loss that ensues. These results led us to hypothesize that changes in intestinal microbiome (IM) composition and metagenome may be independently associated with improvement in metabolic parameters in humans undergoing RYGB. Another aspect of RYGB that has not been studied is the potential changes in oral microbiome (OM) and salivary proteome (SP) and their relationship with weight loss and metabolic improvement. Understanding the OM and SP in morbidly obese patients before and after RYGB is important because shifts in the OM and SP may explain the susceptibility of these patients for oral infections like periodontal disease, which is more prevalent and severe in this population, particularly if T2D is present To our knowledge there are no longitudinal studies the relation between oral and intestinal microbiome before and after bariatric surgery. Furthermore, there are no studies looking at the effect of weight-reduction with the very low calorie diet (VLCD) Optifast regimen on IM, which the investigators plan to do. As IM may contribute to obesity and IR/T2D, the latter being the most dominant feature of the MetS. However, whether specific IM compositions are associated with improvement of obesity, IR/T2D and other features of the MetS is not clear; and the effects of RYGB on IM for treatment of these disorders in morbid obesity have not been well studied. The investigators will conduct a prospective observational study of morbidly obese patients undergoing RYGB, in which the investigators will measure the intestinal microbiome before and after surgery along with insulin resistance and metabolic syndrome. Baseline measurements will be done before the pre-operative run-in with the very low calorie Optifast regimen (800 kcal/d) given before the laparoscopic RYGB (1 week/100 lbs body weight) to reduce the liver size for surgical access. Preoperatively, Optifast likely leads to changes in IM (never assessed) in addition to weight loss and improvement in MetS parameters. Aim: To track the changes in IM structure and function (metagenome) of morbidly obese patients undergoing laparoscopic RYGB through 3 stages - a) before vs. after pre-op Optifast weight reduction treatment 24; and post-op RYGB at b) 1 month; and at c) 6 months. The investigators will correlate the specific changes in IM through these stages, to improvement in IR and other features of the MetS. At the same time points the investigators will also measure the OM, salivary flow rate and SP, as well as oral inflammatory load.