In Gut Research’s Latest Advance, Bacteria From Thin Humans Can Slim Mice Down
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 growing fascination with gut bacteria and their role in health and diseases like irritable bowel syndrome and Crohn’s disease. 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 that got bacteria from lean twins stayed lean.
The study, published online Thursday by the journal Science, is “pretty striking,” said Dr. Jeffrey S. Flier, an obesity researcher and the dean of the Harvard Medical School, who was not involved with the study. “It’s a very powerful set of experiments.”
Michael Fischbach of the University of California, San Francisco, who also was not involved with 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 the next step will be to try using gut bacteria to treat obesity by transplanting feces from thin people.
“I have little doubt that that will be the next thing that happens,” Dr. Fischbach said.
But Dr. Flier said it was 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 I. Gordon of Washington University in St. Louis, the senior investigator for the study, also urged caution. He wants to figure out which bacteria are responsible for the effect so that, eventually, people can be given pure mixtures of bacteria instead of feces. Or, even better, learn what the bacteria produce that induces thinness and give that as a treatment.
While gut bacteria are a new hot topic in medicine, he added that human biology is complex and that 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, with the right diet, it might be possible to 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 that 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 that is thin.
Although researchers suspected that gut bacteria might play a role in human obesity, it has been difficult to get convincing evidence. While 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 Dr. 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 that 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 their weights.
Five weeks after they got human gut bacteria, the mice with bacteria from the fat twins had about 15 to 17 percent more body fat than those that had bacteria from thin twins. They also had some of the metabolic changes associated with obesity.
Next came what Dr. 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 one another’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 that 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 Dr. Gordon’s colleague Vanessa K. Ridaura had an idea. From a national survey about 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 and drying fruits and vegetables and combining them with 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 that 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 took over only when the mice got pellets that were rich in fruits and vegetables and low in fat.
“This is all weird and wonderful,” said Robert W. 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.
Dr. 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,” Dr. Khoruts said, but added that 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.
Those were people with no other treatment options, Dr. 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,” Dr. Karp said, noting that that was his personal opinion.
But he added that he was not sure weight loss centers would take that cautious approach.
“It would not surprise me if someone somewhere starts doing it,” Dr. Karp said.