Oklahoma researchers use germ-free mice to study human gut bacteria
Oklahoma City — Mice have a reputation as filthy disease carriers, but the little red-eyed residents of the Oklahoma Medical Research Foundation's new lab are cleaner than any human could hope to be.
The rodents were bred to be germ-free so researchers could use them to study how certain types of bacteria affect their risk of disease. And while treatments that work in mice don't always translate well to humans, studying them is a first step toward learning how bacteria shape our health.
The average person carries trillions of bacteria, and research on humans has found links between carrying certain mixes of bacteria and diseases such as diabetes, depression, obesity and malnutrition, said Sai Tummala, executive vice president of comparative medicine at OMRF.
The issue doesn't seem to be that one type of bacteria in your colon makes you sick in the way that infection with the germ that causes cholera, for example, will send you straight to a hospital. Instead, it appears that when the normal bugs in your digestive system get out of balance — maybe due to antibiotic use or your diet choices — the imbalance has effects that go beyond your intestines.
Finding that people who have a disease also tend to have more of a certain type of bacteria in their guts doesn't prove that the bacteria caused the problem, however — some other factor could drive both. The goal with the mice is to be able to manipulate the bacteria in their bodies and observe whether their health changes, so researchers can determine whether the imbalance is causing disease, Tummala said.
“It's the next frontier in research,” he said.
In the bubble
To get to the new lab, visitors have to wear sterile suits over their clothes, cover their hair and shoes and stand in a booth that uses pressurized air to blow off any contaminants they may be carrying. Anything that comes into the plastic “bubble” where the mice live, including their food and bedding, also must be sterilized, said Heather Splawn, veterinary training and health coordinator.
- Related to this story
- Video: Studying microflora with germ-free mice (2017-11-10)
“We can't even use regular trash bags (to remove their bedding) because there's no way to clean them,” she said.
The germ-free mice behave normally and are about as healthy as normal lab mice, though obviously they can't get infections in a sterile environment, Splawn said. Another difference is that their urine and feces don't have a smell, because bacteria aren't breaking them down.
The lab was designed to be a shared resource for scientists from multiple institutions, Tummala said. The first project, testing the effect of different bacteria on inflammation in the colon, is scheduled to start later this month, he said. The lab currently has two bubble habitats, and could eventually have as many as 200.
The facility got an accidental view of the potential power of bacteria when a researcher modeling autoimmune disease in mice was recruited, Tummala said. That was before OMRF started working on the lab about six months ago.
The researcher came from Virginia with mice that had been genetically modified to have symptoms like Sjogren's syndrome, a disease where the immune system attacks the tear ducts and salivary glands. But shortly after the mice arrived in Oklahoma, they stopped showing symptoms, despite efforts to change their environment as little as possible. Fecal samples showed they were carrying different bacteria in Oklahoma than in Virginia, Tummala said.
“That was kind of an ‘a-ha' moment for us,” he said.
Scientists are moving toward a consensus that the mix of bacteria in people's intestines is important, and that doctors might prescribe certain types of bacteria or diets to influence them in the future, Tummala said. Companies that make dietary supplements have picked up the probiotic label with enthusiasm, but at this point, it's impossible to say what types of bacteria might benefit any particular person, he said.
“There's a lot of information we don't know,” he said. “We're just scratching the surface.”