The trillions of bacteria that live in the gut – helping digest foods, making some vitamins, making amino acids – may help determine if a person is fat or thin.
The evidence is from a novel experiment involving mice and humans that is part of a burgeoning fascination with gut bacteria and their role in health and diseases such as irritable bowel syndrome and Crohn's syndrome. In this case, the focus was on obesity.
Researchers found pairs of human twins in which one was obese and the other lean. They transferred gut bacteria from these twins into mice and watched what happened. The mice with bacteria from fat twins grew fat; those who got bacteria from lean twins stayed lean.
The study, published online Thursday by the journal Science, is "pretty striking," said Dr. Jeffrey Flier, an obesity researcher and the dean of Harvard Medical School who was not involved with the study. "It's a very powerful set of experiments."
Dr. Michael Fischbach of the University of California, San Francisco, who also was not involved in the study, called it "the clearest evidence to date that gut bacteria can help cause obesity."
"I'm very excited about this," he added, saying that the next step will be to try using gut bacteria, by transplanting feces from thin people, in an attempt to treat obesity in humans.
"I have little doubt that that will be the next thing that happens," Fischbach said.
But Flier said that it is far too soon for that.
"This is not a study that says humans will have a different body weight," if they get a fecal transplant, he said. "This is a scientific advance," he added, but many questions remain.
Dr. Jeffrey Gordon of Washington University, the senior investigator for the new study, also urged caution. He wants to figure out which bacteria are responsible for the effect so that, eventually, people could be given pure mixtures of bacteria instead of human feces. Or, even better, learn what the bacteria produce that induces thinness and give that as a treatment.
And, he added, while gut bacteria are a new hot topic in medicine, human biology is complex and obesity in particular has many contributors, including genetics and diet.
In fact, the part of the study that most surprised other experts was an experiment indicating that, given the right diet, it might be possible to really change the bacteria in a fat person's gut so that they promote leanness rather than obesity. The investigators discovered that given a chance, and in the presence of a low-fat diet, bacteria from a lean twin will take over the gut of a mouse who already had bacteria from a fat twin. The fat mouse then loses weight. But the opposite does not happen. No matter what the diet, bacteria from a fat mouse do not take over in a mouse who is thin.
Although researchers suspected gut bacteria might play a role in human obesity, it has been difficult to get convincing evidence. Although there are often differences in gut bacteria in fat and lean people, they could be a cause – or an effect – of obesity. And gut bacteria vary from individual to individual, making it very difficult to decide which, if any, affect body weight.
Those obstacles led Gordon and his colleagues to look for those rare sets of twins in which only one twin is fat. That allowed them to cancel out much of the effect of genetics and environment. They gave the twins' fecal bacteria to mice who were born and reared in a sterile environment and had no bacteria of their own as a result. The mice were genetically identical, so genetic factors played no role in determining their weights.
Five weeks after they got human gut bacteria, the mice with bacteria from the fat twins had about 15 percent to 17 percent more body fat than those who had bacteria from thin twins. They also had some of the metabolic changes associated with obesity.
Next came what Gordon calls the "Battle of the Microbiota," referring to the collection of gut microbes.
The researchers put mice with gut bacteria from lean twins in the same cage as mice with gut bacteria from obese twins. Mice housed together eat each other's droppings, so the mice in the cage naturally end up sharing gut bacteria. He also put in germ-free mice to determine which collection of gut bacteria they would get. Or would they get a mixture?
That led to the discovery that bacteria from the lean twins took over in the mice who started out with bacteria from the fat twins, resulting in weight loss and a correction of the metabolic abnormalities the mice had developed. But the mice were eating standard mouse food, which is very low in fat.
Then Gordon's colleague Vanessa Ridaura had an idea.
From a national survey of what Americans eat, she and her colleagues determined the diets of those eating the most fruits and vegetables and the least saturated fats and the diets of those at the opposite end of the spectrum. With that information, they created mouse food pellets of the same two compositions by cooking, combining and drying fruits and vegetables and fats in the right proportions. They then repeated the experiment, putting fat and lean mice together in a cage and giving them one of the two types of food.
The fat mice who got food high in fat and low in fruits and vegetables kept the gut bacteria from the fat twins and remained fat. The thin twins' gut bacteria only took over when the mice got pellets that were rich in fruits and vegetables and low in fat.
"This is all weird and wonderful," said Dr. Robert Karp, a program director for genetics and genomics at the National Institute of Diabetes and Digestive and Kidney Diseases.
And it raises questions of what comes next. Gordon's plan to isolate the bacteria or their products responsible for leanness "could take many decades," said Dr. Alexander Khoruts, a gastroenterologist at the University of Minnesota.
"I am not down on this approach," Khoruts said. But, he said, it would be a lot quicker to try fecal transplants.
They have worked in one situation – people with a terrible gut infection with the bacteria Clostridium difficile get better when given feces from healthy people.
These were people with no other treatment options, Karp noted, but, he said, perhaps obese people who have not done well after bariatric surgery might be in the same desperate situation.
"Maybe we could try it out, very, very gingerly, very, very carefully," he said, noting that that is his opinion.
But, he added, he is not sure if weight loss centers will take that cautious approach.
"It would not surprise me if someone somewhere starts doing it," Karp said.