Bugs in the Hood

By Lyn Smith Gloria, Carlson College of Veterinary Medicine

In our intestines, billions of microbes live together like the residents of a teeming metropolis. They occupy neighborhoods and meet on the streets, back alleys and cul-de-sacs of our digestive networks. They even communicate with a kind of microbial Facebook. They function in a symbiotic relationship with each other and with our own cells.

In the past decade, scientists have discovered how important these bugs are in digesting our food, building our immune systems, maintaining stable glucose levels and other jobs that are critical to good health.

All this new information has led to a boom in the marketing of probiotic supplements that contain so-called “beneficial bacteria.” In fact, probiotics have become a $50 billion industry worldwide, despite a lack of proof that they work.

“It’s not that simple,” says Natalia Shulzhenko, assistant professor in the Carlson College of Veterinary Medicine at Oregon State University. “We need to identify the ones that are really critical, and it might not be specific species but rather what functions they perform that make an impact.”

Shulzhenko’s research focuses on understanding how the cells in the human immune system communicate with other systems and with the microbes in our intestines. To this end, her lab has developed special mice that have been raised from birth in a sterile environment. These mice have no microbes in their intestines — and very few immune cells — which enables Shulzhenko to study them in a controlled environment. “We can introduce one specific microbe that we think is important, and look at exactly what it is doing,” she says.

Using the mice and gene studies of specific bacteria, Shulzhenko discovered a three-way interaction, or “crosstalk,” between the immune system, the intestinal lining and intestinal microbes. “These communities are much more complex than we originally thought,” she says.

Antibiotics and the modern diet of high-fat, processed foods can disrupt these communities in our intestines, causing inflammation and inhibiting the production of antibodies. Shulzhenko found that this disruption caused epithelial cells (located at tissue surfaces) in the lining of the intestines to switch jobs: Instead of efficiently processing glucose and other nutrients, they took over the immune functions of the missing antibodies.

Shulzhenko has used all the information she has gathered to create a kind of neighborhood map of intestinal microbes that identifies their average abundance and the relationships between them. She calls this the “transkingdom network” and is using it to focus her research on metabolic function and type 2 diabetes.

In a recently published study, Shulzhenko described the influence of a specific gut microbe, Akkermansia muciniphila, on glucose tolerance, our ability to manage supply and demand for this vital energy source. These bacteria control a substance called interferon gamma, which has been shown to negatively impact glucose tolerance.

Shulzhenko’s research and other studies could potentially lead to the development of probiotics that target specific diseases like diabetes.