The gut microbiome – a “garden” of bacterial, viral and fungal genes – may play a substantial role in development of obesity and diabetes in humans, say scientists.
The findings, published in the journal Mucosal Immunology, highlights the potential to prevent obesity and diabetes by manipulating levels and ratios of gut bacteria, and modifying the chemical and biological pathways for metabolism-activating genes.
“This study adds to our understanding of how bacteria may cause obesity, and we found particular types of bacteria in mice that were strongly linked to metabolic syndrome,” said David Hackam, surgeon-in-chief at Johns Hopkins Children’s Center in the US.
“With this new knowledge we can look for ways to control the responsible bacteria or related genes and hopefully prevent obesity in children and adults,” said Hackam.
Metabolic syndrome, a cluster of conditions including obesity around the waist, high blood sugar and increased blood pressure, is a risk factor for heart disease, stroke and diabetes. While no precise cause for metabolic syndrome is known, previous studies of Toll-like receptor 4 (TLR4), a protein that receives chemical signals to activate inflammation, have suggested that TLR4 may be responsible in part for its development.
How and why TLR4 may be responsible for metabolic syndrome, however, has been unclear, said Hackam.
The researchers fed both groups of mice “standard chow,” or food with 22 % fat calories, for 21 weeks.
Compared to normal mice, those lacking TLR4 showed a series of symptoms consistent with metabolic syndrome, such as significant weight gain, increased body and liver fat, and insulin resistance.
The researchers then fed both groups of mice a high-fat diet composed of 60 % fat calories for 21 weeks to find out whether diet would affect the development of metabolic syndrome. The genetically modified mice gained significantly more in weight and had greater body and liver fat than the normal mice.
To confirm the role of TLR4 expression in the intestinal epithelium, the researchers genetically modified three more groups of mice: one group expressed TLR4 only in the intestinal epithelium, another group lacked TLR4 in all body cells and the third group lacked TLR4 only in white blood cells.
Compared with normal mice, belly and small intestine fat was higher in mice lacking TLR4 only in the intestinal epithelium. This provides further evidence that deleting TLR4 specifically from the intestinal epithelium is required for developing metabolic syndrome.
To investigate the role the bacterial makeup of the gut had on the mice, researchers administered antibiotics to the normal and TLR4 intestinal epithelium-deficient mice. Antibiotics significantly reduced the amount of bacteria in the intestinal tract and prevented all symptoms of metabolic syndrome in the mice that lacked TLR4 in their intestinal epitheliums.
This demonstrates that bacterial levels can be manipulated to prevent the development of metabolic syndrome, researchers said.