Scientists make human microbiome from scratch
Our bodies are home to hundreds or thousands of species of microbes — nobody is sure quite how many. That’s just one of many mysteries about the so-called human microbiome.
Our inner ecosystem fends off pathogens, helps digest food and may even influence behavior. But scientists have yet to figure out exactly which microbes do what or how. Many studies suggest that many species have to work together to do each of the microbiome’s jobs.
To better understand how microbes affect our health, scientists have for the first time created a synthetic human microbiome, combining 119 species of bacteria naturally found in the human body. When the researchers gave the concoction to mice that did not have a microbiome of their own, the bacterial strains established themselves and remained stable — even when the scientists introduced other microbes.
The new synthetic microbiome can even withstand aggressive pathogens and cause mice to develop a healthy immune system, as a full microbiome does. The findings were published last month in the journal Cell.
A better understanding of the microbiome could potentially lead to a powerful way to treat a host of diseases. Already, doctors can use the microbiome to treat life-threatening gut infections of the bacteria Clostridium difficile. They just have to transplant stool from a healthy donor, and the infection usually goes away.
“It works shockingly well,” said Dr. Alice Cheng, a gastroenterologist at Stanford University who led the new study.
Cheng and her colleagues can now use the new synthetic microbiome to learn about the role of each individual microbe, knowledge that could help doctors tackle other disorders. For example, the scientists could mix a cocktail of 118 of the 119 species in the lab and then see how the modified microbiome affects the health of mice.
Before the 21st century, most of what was known about the human microbiome came from the few species that researchers managed to grow in a petri dish. In the early-2000s, scientists made a major advance by fishing DNA from samples of human spit, stool and skin. With those genetic sequences in hand, they created a catalog of species that live in our bodies.
The list was startlingly long, and many species were new to microbiologists. Making matters more confusing, most species live in some people but not others. There is no one human microbiome.
A number of researchers turned to mice to get better acquainted with some of these unfamiliar organisms. They reared germfree animals in sterile cages and then put a broth made from human feces into the animals’ intestines. The microbes in that fecal transplant then started replicating in the animals.
Some researchers have taken on this challenge by giving germ-free mice a single species of microbe and observing its effect. But those experiments have their own limits, since many microbes don’t work properly without ecological partners to help them.
Scientists have tried giving germ-free mice combinations of microbes. But so far, even the best efforts have left mice transplanted with fewer than 20 species — not the hundreds that live in humans. These miniature microbiomes leave the mice with poorly developed immune systems and metabolisms. “You get a mouse that doesn’t work,” said Lora Hooper, an immunologist at the University of Texas Southwestern Medical Center who was not involved in the new study.