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Biomedicine

Transplanting Gut Microbes to Treat Disease

Scientists examine new ways to manipulate the microorganisms within us.

Earlier this summer, scientists reported the success of an unusual medical transplant; a woman with a life-threatening Clostridium difficile infection was treated, and apparently cured, with an injection of some of her healthy husband’s gut bacteria. Researchers are now exploring the effects of this type of transplant in greater detail. They hope to eventually treat a wide range of ailments–from bowel diseases to obesity, diabetes to depression–by manipulating the bacteria that live in the human gut.

The microbes that inhabit our digestive tract, skin, mouth, and other body parts–known collectively as the human microbiome–play a key role in human health, influencing metabolism, immune function, and more. (Each of us contains roughly 10 times as many microbial cells as human ones.) Scientists are exploring a number of ways to manipulate one’s microbes, including eating foods such as yogurt that contain healthy bacteria. But transplanting entire microbial populations may provide a more powerful way to overhaul our intestinal ecosystems. Eating more yogurt, for instance, hasn’t helped people with C. difficile infections, says Rob Knight, associate professor of chemistry and biochemistry at the University of Colorado at Boulder.

Knight and collaborators from Barcelona, Spain, are studying microbe transplants in rodents with the hope of more effectively applying the approach to people. In a paper published last week in the journal Genome Research, the researchers demonstrated that they could successfully transplant the entire microbial community of one healthy rat’s digestive system into another’s. After three months, the recipient’s microbiome more closely resembled the donor’s, though the two microbiomes were not identical.

They also reported that antibiotics, which they had hoped would make the colonization easier, actually impeded growth. Animals treated with the drugs prior to the transplant ended up with a less diverse microbiome, which also had less resemblance to the donor’s. Though the finding needs to be confirmed in people, it suggests that antibiotics might be counterproductive in the transplantation process, says Knight.

Unlike with traditional transplants of organs or tissue, the rats showed no evidence of rejection. “We didn’t notice anything. They were not sick–not even diarrhea,” says Chaysavanh Manichanh, a researcher in the Digestive System Research Unit at the University Hospital Vall d’Hebron Research Institute in Barcelona and the paper’s first author.

Jo Handelsman, a professor in Yale University’s department of molecular, cell, and developmental biology, says the idea of transplanting an entire microbiome is very provocative, because we don’t yet understand which microbes are important and which aren’t.

“Sometimes when we try to define every gene and every organism that needs to be there, we miss things. That’s the attraction of taking a real community and transferring the whole thing,” she says. Eventually, we will have a better handle on which microbes are most important, and on what we can eat–or avoid eating–to foster the growth and stability of “good” microbe communities, she says.

The researchers initially hypothesized that transplantation would be helped by first clearing out the recipient’s gut microbes with antibiotics, according to Manichanh. But they discovered that the antibiotics were so powerful that they interfered with the establishment of the new microbial colonies. The rats that didn’t get antibiotics showed more changes in their flora than the ones that did.

George M. Weinstock, a professor of genetics at Washington University in St. Louis and associate director of the school’s Genome Center, says it’s too soon to tell whether similar transplantation will work in people, and if so, for which diseases. While anecdotal experiments have shown that changing someone’s microbiome can be a treatment for disease, definitive experiments are lacking, he says.

David A. Relman, a professor of medicine and of microbiology and immunology at Stanford University, says it also remains to be seen whether the transplantation can be standardized to produce reliable and reproducible results. Getting someone else’s gut microbes could conceivably have a positive effect on disorders that involve bacterial overgrowth, but could also have potentially dangerous effects. This new study followed the rats for three months and found that the new colonies of microbes were stable. But future studies will have to follow the transplant recipients over a longer term, Relman says.

The next step in their research, Manichanh says, is to see if a microbiome transplant can affect the course of a sick animal’s disease. She and her team first plan to look at irritable bowel syndrome. They are already working to catalog the microbiotic diversity of people with the disorder, and hope to associate specific strains of bacteria with the disease.

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