The connection between gut bacteria and obesity has gained some weight, with new findings demonstrating links in mice among immune-system malfunction, bacterial imbalance and increased appetite.
Mice with altered immune systems developed metabolic disorders and were prone to overeating. When microbes from their stomachs were transplanted into other mice, they also become obese.
"This supports the notion that some of the increase in obesity may be because of changes to gut bacteria," said Andrew Gewirtz, an Emory University immunologist and co-author of the study, published March 4 in Science.
The findings are the latest in a growing body of research about the long-unappreciated role of bacteria in our bodies. Bacterial cells actually outnumber human cells in the body: From an outside perspective, people are not so much individual organisms as symbiotic human-bacteria collectives.
Disturbances to internal bacteria have been linked to asthma, cancer and many autoimmune diseases. Gut flora have also been linked to obesity. In 2006, researchers led by Washington University microbiologist Jeffrey Gordon documented bacterial changes in the stomachs of mice who became obese on high-fat diets.
When transplanted, their gut bugs turned other mice obese, suggesting that altered bacteria were not only an effect of weight gain, but a cause. The Science findings complement those, but also emphasize the immune system's role and the possibility of appetite change.
"The reason why people are eating too much may not simply be because unhealthy food is cheap and available, but that their appetites may be driven by changes in gut bacteria," said Gewirtz,
In the Science study, Gewirtz and Emery microbiologist Matam Vijay-Kumar studied a strain of mice deficient in TLR-5, a gene that's required for immune systems to recognize many types of bacteria.
They found that TLR-5–deficient mice are about 20 percent heavier than regular mice. They overeat, have high blood pressure and high cholesterol, and are insulin-resistant. In humans, that constellation of conditions is known as metabolic syndrome, and in both people and mice leads to obesity and diabetes.
Earlier research had found unusual patterns of bacteria in the guts of those mice. When the researchers transferred bacteria from the stomachs of TLR-5–deficient mice to mice without gut bacteria, the recipients started to eat more, and soon developed metabolic syndrome.
"It's a really exciting paper. It confirms and supports a lot of the findings we've had, and adds in the interaction between gut bacteria and the immune system," said Peter Turnbaugh, a systems biologist who moved from Jeffrey Gordon's lab to Harvard University. "It's been thought for a long time that maybe the immune system is an important regulator of what's in the gut."
How gut bacteria produce metabolic changes isn't known. They may process nutrients directly, or alter the activity of metabolism-regulating genes.
Mice used in the research are not considered exact models of bacteria and obesity in humans. Instead they're models of these sorts of relationships likely to exist in people. Gewirtz's team is now investigating whether people with metabolic syndrome have unusual gut bacteria.
The findings don't suggest obesity is literally contagious, said Turnbaugh. But they do raise the possibility of altering the composition of gut bacteria, either directly or — more realistically — by learning what sort of environmental and lifestyle factors produce obesity-causing bugs.
One possible culprit is the ubiquitous presence of antibiotics, both prescribed and in the environment, said Gewirtz.
"It may be that an unintended consequence of this has been the upset of bacterial populations that are promoting obesity and metabolic syndrome," he said.
Image: Left, regular and TLR-5–knockout mice. Right, a comparison of their insulin-producing islet cells./Andrew Gewirtz
See Also:
- Internal Bacterial Imbalance Leads to Asthma
- Gut Bacteria Affect Almost Everything You Do
- Gut Bacteria, Language Analysis Solve Pacific Migration Mystery ...
Citation: "Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor-5." By Matam Vijay-Kumar, Jesse D. Aitken, Frederic A. Carvalho, Tyler C. Cullender, Simon Mwangi, Shanthi Srinivasan, Shanthi V. Sitaraman, Rob Knight, Ruth E. Ley, Andrew T. Gewirtz. Science, Vol. 327, No. 5970, March 4, 2010.
Brandon Keim's Twitter stream and reportorial outtakes; Wired Science on Twitter. Brandon is currently working on a book about ecological tipping points.
