Bariatric surgery alters the gut microbiota and blood glucose in mice

Abstract

The prevalence of obesity is increasing globally. Obesity is characterized by increased fat mass and is a risk factor for type 2 diabetes (T2D). Obesity is associated with hyperglycaemia, hyperinsulinemia, insulin resistance and chronic inflammation. Currently, the most effective and durable treatment for obesity and its comorbidities is bariatric surgery. Bariatric surgery changes food intake, energy balance and the composition of gut microbiota. Bariatric surgery can lower blood glucose and put T2D into remission. It was unknown if bariatric surgery-induced changes in the gut microbiota was an independent yet sufficient factor to lower blood glucose. Fecal microbiota transplantation (FMT) was performed on conventional (specific-pathogen-free, SPF) and germ-free (GF) mice using fecal material obtained from patients before surgery and 12 months after bariatric surgery. We tested FMT into mice from the same patients before and after vertical sleeve gastrectomy (VSL) and biliopancreatic diversion with duodenal switch (BPD/DS). FMT did not alter body weight, fat mass, glucose tolerance or glucose transporter mRNA expression in all intestine segments in SPF mice. FMT lowered blood glucose during an oral glucose load in GF mice receiving bacteria after VSL and BPD/DS bariatric surgery. Post-BPD/DS surgery FMT decreased Glut1 transcript level in the ileum and increased Glut1 transcript level in the TA muscle of GF mice, but did not change GLUT1 protein levels. Post-BPD/DS surgery FMT also decreased goblet cell count, villus height and crypt depth in the ileum of GF mice. We conclude that changes in the gut microbiota caused by bariatric surgery is a standalone factor that can lower blood glucose and alter gut morphology.