Over the last decade, we've discovered that the microbes that live in your guts can affect your body weight. Researchers can even make mice fatter or thinner by implanting them with gut microbes from obese or lean humans. Could this lead to microbe-based therapies for obesity?
With the trillions of bacteria and other microbes living in your body, you're never really alone. People can certainly survive without these microorganisms, known collectively as the microbiome, but they'll be unhealthy. Your microbiome does a lot of good for your body, helping you break down food as well as cleansing toxins from your organs (of course, not all microbes are so nice).
Recent research has shown that the demographics of our tiny overlords remain largely stable over time, but certain factors, such as our long-term diets, do affect the microbial composition of our guts. And this is important because obese and non-obese people appear to have different proportions of certain gut microbes.
A few years ago, microbiome researchers with the Washington University in St. Louis showed that microbial communities from human fecal samples could successfully colonize the guts of germ-free mice after implantation. And by switching the mice from a diet low in fat and high in plant-based carbohydrates to a "Western" diet that's rich in fat and sugar, they could rapidly change the microbial composition of the mice, while also making them fatter.
But this raised a number of questions. For example, could microbial communities from obese people transmit obese traits to mice? If so, could changing the diet counter that affect? What does this all mean for fecal transplants in humans?
Implanting Mice with Human Gut Microbes
To answer some of these lingering questions, the WU scientists and their colleagues conducted a few experiments. To start, they recruited four pairs of human female twins — in each pair, one sibling was obese and the other was not. They then transplanted the intestinal microbiota in fecal samples from the humans into the guts of germ-free mice.
They found that the mice that received microbes from an obese twin (obese mice) gained more fat than the mice that received microbes from a lean twin (lean mice), despite being on the same diet and eating the same amount of food. The researchers saw the same thing happen when they inoculated germ-free mice with bacteria cultures derived from the twins. This difference in fat accumulation, they found, was due to metabolic differences brought on by the different microbial communities.
The team then wondered what would happen if the mice mixed-and-matched their gut microbes. To find out, they placed pairs of the different mice in the same cages — since mice readily eat feces, they quickly exchanged microbes. After 10 days, the obese mice slimmed down and adopted the metabolic profile of their leaner friends; the lean mice, on the other hand, appeared unaffected by the microbes and metabolism of the obese mice.
After analyzing the bacterial communities, the researchers found that certain members of the Bacteroidetes phylum that were in the lean mice colonized unoccupied niches in the obese mice — this triggered metabolic changes that reduced the obese mice's fat accumulation. Interestingly, the researchers didn't see these changes when they cohoused obese mice with lean mice harboring only a selected set of Bacteroides species (including many that they linked to reducing fat). This odd find suggests that the bacteria — including non-Bacteroides species — interact in complicated ways to change metabolism and reduce body mass.
A final experiment showed that diet plays a heavy role in the matter. When the cohabitating mice consumed food high in fiber and low in saturated fat, the microbes from the lean mice were able to supplant themselves in the guts of the obese mice, just as before. But when the mice had a diet low in fiber and high in saturated fats, the Bacteroidetes from the lean mice could not colonize the guts of the obese mice.
Perhaps the most intriguing finding of Ridaura et al. is that microbial protection from increased adiposity is only possible against the backdrop of a suitable host diet. It may be that future microbiota-based therapies for an obese individual will require an alteration in diet to aid colonization by beneficial microbes. This offers a potentially synergistic approach, whereby reduced caloric intake and increased fiber consumption not only have a positive impact on energy balance but might also promote transplanted microbial communities that are associated with leanness.
Doctors have recently used fecal transplants to alter patient's gut microbiota, helping to rid them of certain ailments, such as recurrent Clostridium difficile infections. The new study suggests that the procedure, or other microbiome-altering treatments, may be able to help obese people slim down. But such therapies, like many other weight-loss treatments, will only be effective if used in conjunction with a healthy diet.