Obesity is more than a cosmetic concern, because it increases a person’s risk for developing high blood pressure, diabetes, and many other serious health problems. It’s well understood that consuming more calories than you expend through exercise and daily activities causes weigh gain. But with about one in every three American adults now considered obese, researchers are attempting to identify additional factors that affect a person’s tendency to gain and retain excess weight.
In the April issue of Mayo Clinic Proceedings, researchers from Mayo Clinic Arizona and the Biodesign Institute at Arizona State University examine the role that bacteria found in the human gastrointestinal tract play in regulating weight and the development of obesity.
Known as gut microbiota, the trillions of bacteria that populate the human gastrointestinal tract perform a variety of chores. These “friendly” microbes help extract calories from what we eat, help store these calories for later use, and provide energy and nutrients for the production of new bacteria to continue this work.
According to John DiBaise, M.D., a Mayo Clinic Arizona gastroenterologist and lead author of the Mayo Clinic Proceedings article, several animal studies suggest that gut microbiota are involved in regulating weight and that modifying these bacteria could one day be a treatment option for obesity. Other authors of the article include: Husen Zhang, Ph.D., Rosa Krajmalnik-Brown, Ph.D., and Bruce E. Rittmann, Ph.D., of the Biodesign Institute’s Center for Environmental Biotechnology; and Mayo Clinic Arizona researchers Michael D. Crowell, Ph.D., and G. Anton Decker, MBBCH, MRCP.
One study cited by the authors observed that young, conventionally reared mice have a significantly higher body fat content than a laboratory-bred, germ-free strain of mice that lack these bacteria, even though they consumed less food than their germ-free counterparts. When the same research group transplanted gut microbiota from normal mice into germ-free mice, the germ-free mice experienced a 60 percent increase in body fat within two weeks, without any increase in food consumption or obvious differences in energy expenditure.
The study was the result of a unique collaboration between physicians at Mayo Clinic and environmental remediation experts at the Biodesign Institute, made possible by seed funding provided by the Mayo Clinic to pursue innovative solutions to leading problems affecting human health.
“In environmental biotechnology, we manage microbial communities, usually to improve environmental quality. The idea to improve human health directly by managing the microorganisms in us is an exciting new path for us and a wonderful collaboration between medical and environmental scientists,“ said Rittmann, who directs the institute’s Center for Environmental Biotechnology and is a leading expert in microbial remediation.
Another study reviewed by the authors focused on the gene content of the gut microbiota in mice. Finding more end products of fermentation and fewer calories in the feces from obese mice led researchers to speculate that the gut microbiota in the obese mice help extract additional calories from ingested food.
“These results suggest that differences exist in the gut microbiota of obese vs. lean mice, raising the possibility that the manipulation of gut microbiota could be a useful strategy for regulating energy balance in obese people,” explains Dr. DiBaise.
Although information on the link between gut microbiota and obesity in human subjects is more limited, the authors also present some evidence supporting this connection. One study cited placed 12 obese participants in a weight-loss program for a year, randomly assigning them to either a fat-restricted or carbohydrate-restricted low-calorie diet. Researchers noted distinct differences between lean and obese participants when they monitored the type and number of bacteria found in participants’ stool samples before and after the diet changes.
Another study cited followed children from birth to age seven and analyzed stool samples for the presence of bacteria collected at ages 6 and 12 months. The children who were normal weight at age seven had distinctly different bacteria in their samples than those collected from overweight-obese children, suggesting that differences in the composition of the gut microbiota precede overweight-obesity.
The research team acknowledges that much more research is needed to clarify a number of issues related to the relationship between the gut microbiota and obesity. Future studies need to establish whether the small changes in caloric extraction seen in recent studies can produce measurable weight differences in humans. Second, researchers need to prove or disprove the possible relationship between the gut microbiota and the regulation of weight.
“In particular, it is essential to demonstrate unequivocally whether differences in gut microbiota in obese vs. lean people are the cause or the result of obesity,” says Dr. DiBaise.
Finally, the authors note that the next wave or research should explore the safety and feasibility of modifying the gut microbiota in clinical trials involving humans.
“Although clearly no substitute for proper diet and exercise, manipulation of the gut microbiota may represent a novel approach for treating obesity that has few adverse effects,” says Dr. DiBaise.
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A peer-review journal, Mayo Clinic Proceedings publishes original articles and reviews dealing with clinical and laboratory medicine, clinical research, basic science research and clinical epidemiology. Mayo Clinic Proceeding is published monthly by Mayo Foundation for Medical Education and Research as part of its commitment to the medical education of physicians. The journal has been published for more than 80 years and has a circulation of 130,000 nationally and internationally. Articles are available online at www.mayoclinicproceedings.com.
