In the digestive system, many trillions of bacteria subsist in a delicately balanced ecosystem known as the microbiome. If that balance is disturbed, one result can be inflammatory bowel disease (IBD), an ailment that causes cramping, constipation, and diarrhea.
When the gut’s bacterial equilibrium is out of whack, sentinel proteins called NLRs can detect tissue damage. If activated, NLRs join other proteins to form complexes known as inflammasomes, which in turn promote the production of cytokines, protective proteins that can restore balance.
In a study published May 27 in Cell, a team led by Richard A. Flavell, Ph.D., chair and Sterling Professor of Immunobiology and Howard Hughes Medical Institute investigator, knocked out a vital piece of the NLRP6 inflammasome in mice, which lowered levels of the cytokine IL-18. In the absence of IL-18, one family of gut bacteria overproliferated, displacing others and causing IBD-like inflammation.
In a startling finding, a similarly altered microbiome and propensity for inflammation was picked up by normal mice housed with NLRP6-deficient mice. “The fact that IBD may be transmitted from a susceptible mouse to an ostensibly normal one has potentially profound implications for IBD and other human diseases in which microbiota contribute,” says Flavell.