Mice have a jungle of bacteria, viruses and fungi in their stomachs—and so do we. These microorganisms help both mice and us break down dinner. As we are finding, these bugs also help to regulate the immune system. But we are just starting to learn how these tiny organisms influence us and how changing their composition changes us.
In an attempt to find out, postdoctoral researcher Hachung Chung and her colleagues at Dennis Kasper's Lab at Harvard Medical School tried raising mice with exclusively human gut microbiota.
The human microbes did pretty well in the mice guts (the researchers could tell by culturing fecal pellets from these mice). Interestingly, though, the mice with these microbes did not: their immune systems remained underdeveloped. Even when researchers gave rat microbiota to mice, the mice's immune systems failed to mature. The results were published in the June 22 issue of Cell.
The findings are "perhaps the most definitive that I've seen," says Eugene Chang, a professor of medicine at the University of Chicago, who was not involved in the new study. They show "the critical and specific relationship between host and gut microbes, which is needed for proper development of the host immune response," he says.
The results support the thinking that we humans have coevolved with our microbes—and we're probably not the same without them. "The selection of partners is not by chance," Chang says. And that might explain why as we alter our microbiomes—with antibiotics and superclean upbringings—our immune systems have been changing as well, ushering in increasing rates of autoimmune conditions such as allergies and diabetes. "The consequence is that the balance between us and our microbes, determined through evolution, is upset in ways that impact our health and increase risk for many diseases that were previously uncommon," he notes.
For these experiments, starting germ-free is key. These extra-clean mouse colonies have been living for several years—and many generations—without contact even with the lab environment, so their stomachs remain in a prenatal state (as with humans): sans microbes.
The upside to a germ-free mouse facility is that because the animals' cages are sealed in airtight areas, it smells much better than rooms with standard caged lab mice. The downside is that they take a lot of care. Tools, food, bedding and water have to be sterilized via autoclave and introduced through a double-valve seal. Lab technicians and researchers reach into the cages with plastic gloves that are built into the sealed clear covers similar to the enclosure immunodeficient David Vetter, called the "bubble boy," lived in during his short life. A year after starting at the lab, Chung got married. And perhaps even more so than the food, flowers and guest list, she says, she planned the event largely around the mice.
Chung and her fellow researchers were interested in what happened if these mice got non-mousy microbiomes. To compare reactions with different microbiome compositions, Chung could then give these germ-free mice either human, mouse or rat microbiota (by feeding them microbiomes cultured from feces). One group was kept germ-free as a control.