Inflammation is one the ways the body protects itself against outside invaders. And since the digestive system contains a dense array of bacteria, you might expect the body’s immune response to be in constant overdrive as it confronts a mass of gut microbes.
But that’s not the case, says UO biologist Karen Guillemin.
“One of the major questions about how we coexist with our microbial inhabitants is why we don’t have a massive inflammatory response to the trillions of bacteria inhabiting our guts,” Guillemin said. “How is it that things aren’t going crazy?”
The answer is partially revealed in a new study by Guillemin and a team of researchers that appeared in the online journal eLife. It details the discovery of an anti-inflammatory bacterial protein and helps explain the functioning of one mechanism of the human body’s moderated response to gut bacteria.
The research could someday help inform treatments for a range of human disease associated with excessive inflammation, including inflammatory bowel disease and other intestinal inflammation, and help prevent chronic inflammation throughout the body.
“We’ve been really interested in understanding how animals and their resident microbes negotiate this level of inflammatory response,” Guillemin said. “We set out to test whether gut bacteria actively secrete factors that prevent an excessive inflammatory response.”
In the course of exploring that question, Guillemin and her team discovered the protein Aeromonas immune modulator, also called AimA, which they showed was capable of helping to alleviate intestinal inflammation and the inflammatory response known as septic shock. Through their investigations, researchers found that the protein mutually benefitted the bacteria itself and the animal hosting it by reducing inflammation in both.
Annah Rolig, a former UO postdoctoral fellow and now a research scientist at the Cancer Immunobiology Laboratory at Providence Portland Medical Center, served as the lead author on the paper. Emily Goers Sweeney, a UO research associate, was a co-author.
The research was conducted in zebrafish, which allowed investigators to zero in on the AimA protein and perform numerous tests designed to answer questions such as why bacteria produced such a protein. In examining the structure of the protein, they found similarities to a class of proteins called lipocalins, which include members that modulate inflammation in humans.
To test their theory that the protein was not specifically counteracting inflammation caused by one kind of bacteria but rather acting more generally to temper the immune response, researchers induced inflammation in zebrafish and found that the AimA protein could reduce inflammation.
The study, which was funded by the National Institutes of Health, suggests that other bacteria that live inside humans could be a potentially rich source of novel anti-inflammatory molecules.
“These resident gut microbes are motivated to inhibit inflammation,” Guillemin said, “and they probably have lots of creative ways of dampening down our immune system. We can learn a lot from them about how to design novel anti-inflammatory therapies.”
Co-authors on the paper with Rolig, Guillemin and Sweeney were undergraduate student Lila Kaye, doctoral student Michael DeSantis, postdoctoral researcher Arden Perkins and Allison Banse, a former postdoctoral researcher — all affiliated with the UO’s Institute of Molecular Biology — and M. Kristina Hamilton, a postdoctoral researcher affiliated with the Institute of Neuroscience.
—By Lewis Taylor, University Communications