Some relationships are short lived, but some are for life—like the mutually beneficial partnership between a person and the trillions of bacteria in their gut. But as you and your microbiome grow old together, things can get a little out of whack. Now, a new study in mice suggests aging can indeed change the microbiome—and in some cases, a poop transplant could set it right.
Fecal microbiota transplants, in which the gut microbiome from a healthy person is used to treat someone who is sick, are not a new therapy; the earliest known account dates back to fourth century China, when a doctor named Ge Hong told patients they could cure their diarrhea by consuming fresh stool from a healthy neighbor. More recently, doctors have shown in clinical trials that fecal transplants are an effective treatment for stubborn Clostridium difficile infections; they have also tried to use them for inflammatory bowel disease and constipation.
Biologist Clea Bárcena and her colleagues at the University of Oviedo in Spain knew that aging and age-related diseases often go hand-in-hand with intestinal dysbiosis, in which the balance between the many species of bacteria in the gut is disturbed. So, they decided to examine the microbiota in five children with progeria, a genetic disorder that causes premature aging and death. They also looked at the microbiota of more than a dozen mice genetically modified to exhibit progerialike symptoms.
Both the children and the mice developed increasingly severe intestinal dysbiosis as their disease progressed. But the researchers didn’t find signs of dysbiosis in a group of 17 centenarians, people considered to have “successfully” aged. Instead, the overhundreds had healthy microbiomes, many with a lot of bacteria from a particular phylum called Verrucomicrobia.
Next, the researchers wanted to see whether changing the microbiomes of mice with progeria symptoms made a difference in the progression of their disease. They took bacteria from the feces of healthy mice and put them into the guts of affected mice. Within a few weeks, the progression of symptoms in the mice with progeria began to slow down. They didn’t lose weight as quickly as their untreated counterparts, and they did not experience low blood sugar—both common symptoms of progeria. The treated mice also lived nearly 15% longer, on average, than untreated mice (160 days versus 141 days), the team reports this month in Nature Medicine.
“The possibility to … actually expand life span is really amazing,” says Bárcena, now a postdoctoral researcher at the Wellcome Sanger Institute in Hinxton, U. K.
On the other hand, when healthy mice received a fecal transplant from mice with progeria, their health suffered. They didn’t display typical symptoms of the disease such as accelerated aging, but they gained weight and had slower metabolisms than control mice.
One type of bacterium from the Verrucomicrobia phylum, Akkermansia muciniphila, seemed to play a role in a healthy aging process, the researchers say, possibly by increasing the amounts of secondary bile acids in the gut. The species was more common in centenarians, and low in mice with progeria. When the researchers gave doses of only this species to mice with progeria, their life spans increased as well.
This finding, Bárcena says, could one day help researchers design targeted probiotic treatments for age-related conditions. The next step, she adds, will be to identify additional beneficial bacterial species—and figure out how they work in animal models and humans.
“This is a nice, interesting study,” says Heidi Zapata, a physician at Yale University who has written about the microbiome in aging and age-related diseases. But she cautions that it will be tricky to translate the findings from mice to humans. “I don’t think we’re close to having a pill that we can swallow yet,” she says. “But given the importance of the microbiome, this does portend future possibilities.”