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. / Thesis / Master of Science (MSc) / Type 2 diabetes is a chronic disease that involves high blood sugar (i.e. glucose), which can damage many parts of the body leading to serious complications. Diabetes is a growing global problem and is the seventh leading cause of death. Obesity is one of the largest factors leading to type 2 diabetes. Bariatric surgery reduces obesity and is to date the most effective method to lower blood glucose and reverse type 2 diabetes. Bariatric surgery alters gut anatomy and the types of bacteria that inhabit the gut. Gut bacteria can change obesity and blood glucose levels, but it was not known if the bacterial community present after bariatric surgery was a factor that is sufficient to lower blood glucose. We found that transferring gut bacteria from humans after bariatric surgery into mice lowers the blood glucose and alters the gut barrier structure where food is absorbed. It is not yet clear how this happens, but these findings show that a change in gut microbes is a standalone factor that can alter host blood glucose. Finding the glucose lowering factor in bacteria may be a new treatment to combat type 2 diabetes.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/25945 |
| Date | January 2020 |
| Creators | Chen, Yuk Kwan Cassandra |
| Contributors | Schertzer, Jonathan D., Biochemistry |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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