The link between gut microbial composition and obesity is one of the most fascinating gut links currently being studied. Jeffrey Gordon’s lab at Washington University in St. Louis has consistently produced cutting-edge research that is taking our understanding of the integral role of gut balance—and its interaction with diet—on the development of obesity to fascinating places.
In yet another ground-breaking study led by Vanessa Ridaura, a graduate student in Gordon’s lab, the team found that, “transmissible and modifiable interactions between diet and microbiota influence host biology.”1 They began by transplanting stool from four pairs of female human twins—one twin was lean and one obese in each pair—into germ-free mice (mice bred to have an absence of their own gut bacteria). The mice were fed a standard mouse chow diet low in fat and high in fiber. The mice who received stool—and thus, gut microbes—from the obese women accumulated more fat than did the mice who received microbes from the lean women, even though they were eating the exact same low-fat, high-fiber diet.
The mice receiving the obese microbiome also exhibited higher expression of microbial genes involved in detoxification and stress response (likely because their bodies were under stress and needed more detoxification) and increases in essential amino acids (which the researchers later found was associated with mild glucose intolerance, perhaps the early stages of insulin resistance development, they suggested). The mice receiving the lean microbiome exhibited higher expression of genes involved in digestion of fibers and fermentation to the short-chain fatty acids butyrate and propionate (due to an increase in the ability of these microbes to break down dietary fibers, a function that has been found previously to be linked with a decrease in body weight and fat accumulation).2
The researchers then repeated these studies using a culture collection, rather than the intact stool sample, from the donor human twins. This was done to test the ability of only the culturable microbes found in stool to exhibit the same effects as the entire microbiome. As a matter of practicality, direct fecal transplantation in humans is much more complicated than transplant of a culturable sample that could be replicated and stored in a lab. This would eliminate the need for a human donor for each transplant, a practice that greatly inhibits the progress not only of studies, but also the ability for this research to make its way into the real world for use by patients in need of a treatment for obesity. Like the mice receiving intact stool transplants, the mice receiving the cultured collections from obese humans accumulated more fat than those mice receiving culture collections from lean humans.
Next, the researchers placed mice who had received a culture collection from an obese woman with mice who had received a culture collection from a lean woman. Mice are coprophagic, which is a fancy way of saying that they eat one another’s feces. What is important about this is that when the “obese” mice were placed with the “lean” mice and fed the same low-fat, high-fiber chow, the obese mice began to inherit the microbes from the lean mice and lost the fat they had accumulated, becoming more like the “lean” mice. Very interestingly, the “lean” mice did not inherit the gut microbes of the “obese” mice, nor did they gain any fat. The microbes they had inherited from the lean human protected them against invasion of microbes from the “obese” mice, which protected them against accumulating fat.
The “lean” mice were found to have higher levels of Bacteroidetes, the bacteria found in previous studies to be associated with protection against obesity in both animal and human studies. The researchers tracked the invasion of certain members of Bacteroidetes from the “lean” to the “obese” mice while they were cohoused, suggesting that these bacteria may be responsible for the protection. The researchers hypothesized that Bacteroides (a subgroup of Bacteroidetes) were efficient invaders of “obese” microbiotas because they were able to occupy unoccupied niches in the intestines of the “obese” mice, which did not have as rich a microbial diversity as the “lean” mice.
Next the researchers replicated the cohousing studies and fed the mice a diet made with foods that replicate a low-fat, high fruit and vegetable intake, characteristic of a “healthy” diet. The mice who received culture collections from the obese women had increased body mass and fat accumulation when compared to those mice who received culture collections from lean women, just as they did when eating the mouse chow. Also similarly, when cohoused, the lean mice were protected against obesity and the obese mice inherited Bacteroides species and reverted to a lean profile.
Finally, the researchers again repeated the study, only this time they fed the mice a diet high in saturated fat and low in fruits in vegetables—more reminiscent of the Standard American Diet. The mice receiving culture collections from obese humans still gained more fat and body mass than those receiving culture collections from lean humans. When they were cohoused, however, something different happened. The “obese” mice were no longer able to receive the bacteria from the “lean” mice, and did not revert back to being lean. The SAD diet completely relinquished the ability of the “obese” mice to receive beneficial bacteria from the “lean” mice, and revert back to being lean.
Unfortunately, the researchers did not take a few dietary factors into account. They administered a high–saturated fat diet, but did not take into account other kinds of fats. What if, instead of a low-fat diet, they used a diet high in omega-3 fats? They also did not address diets high in sugar. For example, what was the sugar content of the diet high in fruits and vegetables? And what if they gave a diet high in refined sugar? Would they have found similar results?
In all, the results of these studies highlight the crucial interplay between gut microbes and diet on obesity. This only confirms the message Brenda and I have spread from the beginning—diet is a key component to overall health, primarily because it supports a healthy balance of gut microbes. A diet high in non-starchy vegetables and fruits, healthy fats, lean proteins, nuts, and seeds will feed the beneficial bacteria in your gut that protect you against disease, including obesity. Adding probiotics and prebiotic fibers to this diet will help ensure you house the right microbes in your gut.
- Ridaura VK, Faith JJ, Rey FF, et al., “Gut microbiota from twins discordant for obesity modulate metabolism in mice.” Science. 2013 Sept 6; 341(6150): ePub ahead of print.
- Keenan MJ, Zhou J, McCutcheon KL, et al., “Effects of resistant starch, a non-digestible fermentable fiber, on reducing body fat.” Obesity (Silver Spring). 2006 Sep;14(9):1523-34.