Intestinal Bacteria May Contribute to Developing Obesity and Diabetes
Scientists recently discovered that intestinal bacteria may have an important role in the development of metabolic syndrome, diabetes and obesity. Metabolic syndrome is a constellation of disorders that increases the risk of developing diabetes and cardiovascular disease. Hallmarks include elevated blood sugar, insulin resistance, abnormal blood cholesterol, high blood pressure, fatty liver disease, and obesity – particularly excess abdominal fat. Bacteria that inhabit the digestive tract appear to influence metabolism by affecting the ability to extract energy from food. Furthermore, certain types of intestinal bacteria may play a role in developing obesity, type 2 diabetes, and other aspects of metabolic syndrome. The types of bacteria populating the gut may be determined in part by a protein called Toll-like receptor (TLR) 5. This protein is produced in abundance by cells in the intestinal lining, is important for recognizing microbes, and is part of the innate immune system that can respond to infectious bacteria. Mice lacking TLR5 develop intestinal infections and gain weight, leading scientists to believe that the protein may also influence metabolism, potentially by altering normal gut bacteria.
To further explore the role of intestinal bacteria and TLR5 in developing metabolic syndrome, scientists generated mice that do not produce TLR5 protein. These animals weighed about 20 percent more than normal mice by 20 weeks of age, consumed about 10 percent more food, and produced more body fat compared to their normal counterparts. The TLR5-deficient mice also developed elevated cholesterol levels, increased blood pressure, and insulin resistance. When fed a high-fat diet for eight weeks, both normal and TLR5-deficient mice gained weight but, unlike normal mice, TLR5-deficient animals developed type 2 diabetes and fatty livers. One possible explanation was that TLR5-deficient mice ate a greater quantity of high-fat food. When scientists restricted the amount of high-fat food so that TLR5-deficient mice and normal mice at the same quantity, the TLR5-deficient animals did not become obese, but were insulin-resistant. The investigators thought that the metabolic differences observed between the two strains of mice were due to changes in intestinal bacterial populations resulting from the loss of TLR5. Thus, the researchers compared the gut bacteria between the normal and TLR5-deficient mice and uncovered differences in levels of over 100 types of bacteria. To assess whether the changes in bacteria might be causing the metabolic symptoms, the scientists collected intestinal bacteria from TLR5-deficient mice and transplanted these into “germ-free” mice raised in a bacteria-free environment. Similar to TLR5-deficient mice, the mice who received the transplanted bacteria increased their food consumption, developed insulin resistance, and became obese.
This study demonstrates that bacteria in the gut may contribute to changes in appetite and metabolism. Excess calorie consumption along with the resulting obesity and development of type 2 diabetes could possibly be driven, at least in part, by alterations in intestinal bacteria populations due to compromised bacterial via alterations in biological pathways involving TLR5. Understanding how gut bacteria interact with the intestine could provide a means of modulating eating behavior as well as preventing metabolic syndrome development.
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Vijay-Kumar, M, Aitken JD, Carvalho FA, et al. Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5. Science 328: 228-231, 2010.
