A preclinical study has established a direct correlation between damage to the intestinal lining, inflammation of the joints and the severity of arthritis, suggesting the major role of gut microbiota imbalance in the development of this disorder.
Investigate the links between the severity of arthritis and the weakening of the intestinal wall
In recent years, various studies have shown strong links between abnormalities in the gut microbiota and rheumatoid arthritis, and increased populations of certain types of bad bacteria have often been associated with the severity of the disease. However, the exact way in which gut bacteria can influence joint inflammation remains somewhat unclear.
Several mechanisms have been considered, ranging from intestinal bacteria modulating the development of specific inflammatory cells responsible for arthritis to particular bacterial metabolites contributing to the severity of the disease. In the context of work published in the journal With, the researchers of theUniversity College de Londres examined another causal hypothesis, focusing specifically on the links between the severity of arthritis and the weakening of the intestinal wall induced by bacteria.
« We wanted to know what was going on in the gut and whether changes in the gut wall – which usually acts as a barrier to protect the body from bacteria – were a hallmark of the disease and contributed to its development. “, Explain Claudia Mauri, co-author of the study.
Preliminary results had shown that mice bred to have a genetic predisposition to intestinal permeability also developed signs of severe arthritis. Another mouse model, designed to develop collagen-induced arthritis, exhibited reduced joint swelling when intestinal permeability was improved.
Tell-tale blood tests
Examining human patients, the researchers found that those with rheumatoid arthritis had higher blood levels of lipopolysaccharide (LPS), LPS binding protein (LBP), and intestinal fatty acid binding protein. All of these molecules are known biomarkers of intestinal damage, and the levels of LBP appear to be closely related to the severity of the disease.
« We have shown that in arthritis the intestinal lining is deeply damaged and no longer plays its barrier role properly, with a build-up of white blood cells in the intestine causing inflammation. », Write the researchers. ” When bacteria cross the forbidden border of the intestinal lining, repairing intestinal permeability defects with specific drugs inhibits joint inflammation. »
The team points out, however, that research cannot fully explain the chain of mechanisms linking this weakening of the gut wall to polyarthritis. Thus, although the modulation of the degree of intestinal permeability has been shown to be directly related to joint inflammation, there are still missing links in this relationship, which have not yet been described.
A potential therapeutic target
According to Mauri, however, such results suggest that the intestine could constitute a useful therapeutic target. In particular, she believes that improving intestinal permeability could constitute a new model of effective treatment.
« We have found that using existing drugs that restore the integrity of the gut barrier, which prevent the gut from becoming permeable or inhibit the movement of inflammatory cells to and from the gut, may reduce the severity of arthritis. in preclinical models », Concludes the researcher.