This post was written by Felix Moser, a Postdoctoral Associate in the Voigt Lab.
It is clear that the human gastrointestinal microbiome plays an intricate, even essential role in our health. Recent research has found that it may also play an important role in the adiposity, or fat content, of our bodies.
These findings have emerged from studying the gut microbiomes of people who have undergone gastric bypass surgery. Gastric bypass surgery is among the most successful, if radical, treatments for obesity in modern medicine’s arsenal. During Roux-en-Y gastric bypass surgery, the stomach and part of the small intestine are severed from the digestive tract. The upper end of the stomach is then stapled shut and the removed part of the small intestine is sutured to the wall of the intestine farther down, forming a “Y” shape with the rest of the tract. The new, upper opening of the intestine is then sutured to the esophageal opening. Thus, the esophagus empties directly into the intestine, and the stomach and part of the intestine are “bypassed”. No food passes through the stomach, but stomach and bile acids are still secreted.
Following gastric bypass surgery, patients typically lose >50% of their previous weight and experience dramatic improvements in comorbidities such as Type II diabetes, liver and heart disease. Previously, it was thought that this weight loss resulted from the physical constraints imposed on the newly configured digestive tract. Patients physically could not eat as much and felt full after eating less and therefore lost weight. Makes sense, right?
However, the more closely researchers looked at what was happening to people following surgery, the less the physical explanations made sense. Simply reducing the consumption of food did not lead to the weight loss or changes in satiety experienced by gastric bypass patients. The pattern of secreted bile acids, important signal molecules produced by the liver, is left markedly altered following the surgery. Additionally, the composition of the patients’ microbiomes changed.
In a landmark study published in Science Translational Medicine in 2013, a group led by Dr. Lee Kaplan of the Massachusetts General Hospital (MGH) studied the microbiome composition of obese mice following either gastric bypass or sham surgery. They observed a strong shift in the microbiome composition of mice receiving the gastric bypass surgery favoring Gammaproteobacteria, which usually make up a relatively small portion of most people’s microbiome. Dramatically, they showed that transferring a sample of the gut microbiota from mice that had received gastric bypass surgery was sufficient to reduce the weight in obese germ-free mice by 5% over obese germ-free mice that had received similar samples from mice that had sham surgery. Though this drop in weight was not comparable to getting the surgery itself, it showed that an important role was being played by the microbiome.
These results are supported by more recent studies. Tremaroli, et al. sampled the microbiomes of 14 women nine years after gastric bypass surgery. They observed similar enrichments of Gammaproteobacteria compared to the microbiomes of untreated obese patients. They were also able to show that germ-free mice colonized for two weeks with fecal samples from gastric bypass patients gained 43% less body fat than germ-free mice colonized with fecal samples from untreated obese patients.
So, what’s going on? What is happening to the microbiome to spur the shifts in the ecosystem following surgery, and what is it about the new ecosystem that impacts the patient’s weight? Dr. Kaplan, who spoke to the MIT Microbiome Club at an invited seminar in November, believes that patient’s “adiposity set point” is changed as a result of the surgery via a complex mechanism partially mediated by the microbiome. Though it is unclear to what degree each variable plays a role, changes in nutrient availability and absorption, microbial production of short-chain fatty acids, corresponding changes in secreted bile acids, and changes in activity of the key receptors (e.g. FXR) all seem to play a role, perhaps synergistically. While we don’t yet understand the complex network of interactions that is causing the physiological changes induced by gastric bypass surgery, “we’re beginning to see the edge of the universe” said Dr. Kaplan.
So, could the right microbiome completely cure someone of their obesity? It seems unlikely. Nonetheless, researchers are poised to find out. Ars Technica recently reported that another group at MGH led by Dr. Elaine W. Yu is leading a clinical study in which fecal transplants from lean, healthy individuals will be given to obese patients. Regardless of the outcome of such studies, the data will surely help shed further light on the complex role that the human microbiome plays in health. Maybe someday, with the right combination of microbiota, bile acids, and yes, diet and exercise, the problem of obesity will become more manageable.
Felix Moser is a Postdoctoral Associate in the Voigt Lab. When not engineering new species of bacteria, he likes to run marathons and ride bicycles.