New research from an international team of scientists has uncovered a communication pathway illustrating how the microbiome can influence immune system activity in the gut. The new study describes how molecules produced by gut bacteria help control the activity of a protein known to suppress inflammation.
Around 50 years ago, researchers discovered a protein that seemed to play a major role in reducing the efficacy of cancer treatments. Called P-glycoprotein (P-gp), one of its important functions is to catch and pump out foreign substances that enter cells.
This particular role has made P-gp a focus for cancer researchers as it has been found to significantly reduce the effectiveness of chemotherapy. But more recently P-gp has been found to also play a key anti-inflammatory role in the gut, producing molecules known as endocannabinoids which suppress inflammation.
In cases of chronic intestinal inflammation, such as ulcerative colitis, P-gp expression is reduced. And in those cases of intestinal inflammation researchers also detected major imbalances in gut bacteria populations. But before now it hasn’t been clear exactly how the microbiome could be influencing P-gp expression.
The new research found P-gp expression is influenced by a combination of gut bacteria metabolites. Most importantly the research found P-gp expression is not regulated by one single metabolite or species of bacteria. Instead, P-gp expression is induced by a synergistic combination of a short-chain fatty acid known as butyrate and three secondary bile acids (LCA, DCA, and UDCA).
Optimal P-gp expression was detected only when all of these molecules were working in concert with one another. Merran Dunford, a researcher from the University of Bath working on the study, says the big finding here is the discovery of a cross-talk mechanism highlighting how a healthy microbiome can communicate with the immune systems to keep inflammatory activity in the gut in balance.
"The upshot of this research is that we now know the specific molecules produced by the microbiome bacteria that are linked to P-gp, and hence, a healthy intestine,” says Dunford. “These molecules work in concert to stimulate P-gp to increase the release of endocannabinoid molecules, which suppress intestinal inflammation."
While prior studies have certainly homed in on specific species of gut bacteria that seem to be either expanded or reduced in patients suffering diseases such as ulcerative colitis, the new research suggests keeping gut inflammation in check may be more complex than targeting single bacterial types. Sage Foley, from the University of Massachusetts Chan Medical School, says a future focus on managing a healthy holistic gut microbe community could be key to keeping gut inflammatory diseases in check.
"This highlights the importance of a functioning core microbial community to have maximal impact on the human body,” says Foley. “While even within an individual the relative abundance of microbes can fluctuate, we're beginning to understand the importance of nourishing the microbial community as a whole. Though there is still much to explore, we suspect this may be possible through changes to the diet or through the delivery of groupings of microbes."
The study notes a number of different types of gut bacteria can contribute to the metabolite mix found to influence P-gp expression. And at this stage there is no research indicating particular dietary inputs that can nurture the microbial balance necessary to generate this specific anti-inflammatory activity.
Nevertheless, these findings add another piece to the increasing clear puzzle illustrating how deeply intertwined our immune system is with the population of bacteria living in our gut. Ruth Wakeman, from Crohn's & Colitis UK, is hopeful this work will help generate novel treatments in the future for the millions who suffer from inflammatory bowel disease.
"We welcome research that helps increase understanding of how environmental factors, diet and gut microorganisms may influence conditions such as Crohn's and colitis,” says Wakeman. “We hope that research such as this will lead to new and improved methods of managing the conditions in the future."
The new study was published in the journal Microbiome.
Source: University of Bath