Protein that suppresses inflammation controlled by healthy gut bacteria
New research from the University of Bath, UK, and the University of Massachusetts Chan Medical School (UMass Chan), US, has revealed how major imbalances in gut bacteria influences the expression of a key protein that controls gut inflammation. The international team of researchers are also closer to understand how these bacteria can affect immune system activity in the gut.
The protein in question, called P-glycoprotein (P-gp), allows the intestine to communicate with the immune system through the gut wall. P-gp pumps out foreign substances, including toxins, from the body’s cells; and is at the same time beneficial in helping the intestine maintain homeostasis and subdues inflammation.
The researchers have found that P-gp releases anti-inflammatory compounds known as endocannabinoids into the gut, to maintain a healthy intestine. If these endocannabinoids are reduced or not present, inflammation can flare up.
Optimal P-gp expression – and in turn, endocannabinoids production – is induced by a synergistic combination of a short-chain fatty acid known as butyrate and three secondary bile acids (LCA, DCA, and UDCA) that need to work in concert with one another.
Merran Dunford, a pharmacologist from the University of Bath, said, “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. These molecules work in concert to stimulate P-gp to increase the release of endocannabinoid molecules, which suppress intestinal inflammation.”
Graduate student Sage Foley from UMass Chan highlights the importance of a functioning core microbial community to have maximal impact on the human body. “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 team’s findings provide exciting new opportunities for the future management of inflammatory intestinal diseases that could include dietary changes to promote or sustain P-gp expression in the intestine, thereby protecting against unwanted inflammation.
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