"Probiotic bacterial function is not very clear right now," said Yan, a research associate professor of Pediatrics at Vanderbilt.
Polk and Yan showed that LGG prevented epithelial cells from inflammation-induced apoptosis a kind of cell suicide. They then isolated and characterized two specific proteins secreted by LGG (which they called p75 and p40) responsible for the bacterium's beneficial effects.
In the current study, Yan investigated the mechanisms by which one of these proteins, p40, prevents and treats colitis.
In cell experiments, Yan and colleagues showed that p40 activates the epidermal growth factor receptor (EGFR), a protein critical for cell survival and growth. Activation of EGFR protected epithelial cells in two ways: by preventing both apoptosis and inflammation-induced disruption of the "tight junctions" between epithelial cells, which form a barrier to keep toxic substances and pathogens out of the bloodstream.
To test the isolated protein's effectiveness in animal models of disease, the investigators developed a gel bead system to deliver the protein specifically to the colon while protecting the protein from being degraded by stomach acid and digestive enzymes.
In three different mouse models of intestinal inflammation, they showed that p40 prevented and treated intestinal injury and acute colitis.
This study is one of the few to identify and use individual molecules from beneficial microbes as potential therapeutics. In clinical applications, Yan says that the isolated protein could provide at least two advantages to using whole bacteria.
"One is bioavailability," she said. "Even if you eat live bacteria (as in yogurt), that does not mean 100 percent of bacteria will still be alive (and active) in your body."
|Contact: Craig Boerner |
Vanderbilt University Medical Center