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Metagenome and Bariatric Surgery - New Avenues to Treat Metabolic Disease

Final Report Summary - METABASE (Metagenome and Bariatric Surgery - New Avenues to Treat Metabolic Disease)

Bariatric surgery is the only method to produce long-lasting weight reduction in obese subjects and is also associated with improved metabolism and overall reductions in mortality. We and others have identified the microbiome residing in the human gut to be an important factor in modulating host metabolism. Furthermore, we previously observed that the microbiome was altered in patients with type 2 diabetes. In METABASE we set out to determine whether the microbiome is altered following bariatric surgery and whether the metabolic improvement required an intact microbiome. First, we addressed how Roux-en-Y gastric bypass (RYGB) surgery is affecting the gut microbiome by using metagenomic sequencing of women undergone RYGB nine years earlier. We observed that bariatric surgery produces long-lasting alteration in the gut microbiome, many of the changes similar to those produced by the anti-diabetic medication metformin. By transferring the microbiome before and after surgery into germ-free mice we could demonstrate that the RYGB-associated microbiota produced reduced fat mass gain in the mice, suggesting that the altered microbiome may contribute to the host effects. In the ongoing work we are comparing how different surgical techniques affect the microbiome and also directly addressing whether the microbiome is a prerequisite for metabolic benefits following bariatric surgery by performing sleeve gastrectomy in germ-free mice.