Phospholipase A2-IIA in Chronic Inflammation Driven by the Aging Gut Microbiome

Chronic inflammation in aging drives the onset and progression of many age-related conditions. Researchers here focus on arthritis, but their findings are probably applicable to numerous other issues in aging. The gut microbiome changes with age in ways that promote the growth of inflammatory microbial species, and this may be an important component of age-related inflammation. Researchers here dig into some of the complexity of the microbiome, in search of points of intervention.

Researchers have discovered that a protein naturally present in the gut acts on the microbiota and causes the formation of molecules that exacerbate the symptoms of these diseases. The protein in question, phospholipase A2-IIA, was discovered several years ago in the fluid that surrounds the joints of people with arthritis. The protein was subsequently detected elsewhere in the body, notably in the gut where it is produced in abundance. "It took a long time before we realized that it exhibits antibacterial activity. The protein interacts little with the membrane of human cells, but it has high affinity for bacterial membranes. It binds to these membranes and splits them, releasing small molecules such as fatty acids."

To study the effect of this protein on gut microbiota, researchers used a line of transgenic mice. These mice have the human gene that codes for phospholipase A2-IIA. As they age, they spontaneously develop manifestations of chronic systemic inflammation. Experiments on these mice revealed that phospholipase alters the profile of bacterial lipids that end up in the gut. By releasing fatty acids from the bacterial membranes, the protein produces proinflammatory lipids that exacerbate chronic inflammation and increase the severity of arthritis symptoms in these mice.

These breakthroughs could have therapeutic implications, he says. "The work of both teams suggests that local inhibition of phospholipase may alleviate the inflammatory process that exacerbates certain diseases. It also suggests that blocking the bacterial proinflammatory lipids produced in the gut by this protein could reduce symptoms in people with systemic inflammatory diseases. The next step in our work is to test these ideas in patients with arthritis."


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