An international research team has established a link between gut microbiota and chronic inflammatory diseases such as arthritis. The team has 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.
“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.” said Dr. Boilard.
To study the effect of this protein on gut microbiota, researchers used a line of transgenic mice. 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,” summed up Dr. Boilard.
In another article researchers demonstrated that the action of phospholipase on the gut microbiota of mice also affects psoriasis, another inflammatory disease, as well as skin cancer.
“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.”
Etienne Doré, Charles Joly-Beauparlant, Satoshi Morozumi, Alban Mathieu, Tania Lévesque, Isabelle Allaeys, Anne-Claire Duchez, Nathalie Cloutier, Mickaël Leclercq, Antoine Bodein, Christine Payré, Cyril Martin, Agnes Petit-Paitel, Michael H. Gelb, Manu Rangachari, Makoto Murakami, Laetitia Davidovic, Nicolas Flamand, Makoto Arita, Gérard Lambeau, Arnaud Droit, Eric Boilard. The interaction of secreted phospholipase A2-IIA with the microbiota alters its lipidome and promotes inflammation. JCI Insight, 2022; 7 (2) DOI: 10.1172/jci.insight.152638
Université Laval. “Scientists discover link between gut microbiota and chronic inflammatory diseases like arthritis.” ScienceDaily. ScienceDaily, 25 January 2022. <www.sciencedaily.com/releases/2022/01/220125124029.htm>.