Impressive new research led by a team from University College London is suggesting bacterial imbalances in the gut microbiome may play a major role in the development of rheumatoid arthritis. The preclinical study found damage to the gut lining directly correlates with joint inflammation and arthritis severity.
For some time now researchers have reported consistent links between gut microbiome abnormalities and rheumatoid arthritis, and increasing populations of certain types of bad bacteria have frequently been associated with arthritis severity.
But exactly how bacteria in the gut could influence joint inflammation has so far been unclear. A number of mechanisms have been hypothesized, from gut bacteria modulating the development of the specific inflammatory cells responsible for arthritis, to particular bacterial metabolites contributing to disease severity. This new study investigated a different causal hypothesis, focusing on the links between arthritis severity and a bacteria-induced weakening of the gut wall.
“We wanted to know what was happening in the gut and whether changes to the intestinal lining – which usually acts as a barrier to protect the body from bacteria – are a feature of the disease and contribute to its development,” explains co-lead author Claudia Mauri.
The new study showed mice bred to have a genetic predisposition to gut permeability also developed signs of severe arthritis. A different mouse model, engineered to develop collagen-induced arthritis, was then found to display reduced joint swelling when gut permeability was improved.
Looking at human patients the researchers found those suffering from rheumatoid arthritis had higher blood levels of lipopolysaccharide (LPS), LPS binding protein (LBP), and intestinal fatty acid binding protein. All these molecules are known biomarkers of intestinal damage, and LBP levels in particular were found to correlate with acute disease severity.
“Researchers at University College London have shown that, in arthritis, there is profound damage to the gut lining, which fails to work properly as a barrier, as well as an accumulation in the gut of white blood cells that cause inflammation,” the authors write in the newly published study. “The authors show that, in arthritis, bacteria cross the prohibited border of the intestinal lining and that repairing gut permeability defects with specific drugs inhibits joint inflammation.”
The research cannot completely explain the chain of mechanisms that link this weakening of the gut lining with arthritis. So although modulating the degree of gut permeability was found to directly relate to joint inflammation there are still missing links in that relationship yet to be described.
Mauri does say, however, these finding do indicate the gut could be a useful therapeutic target. She particularly speculates that improving gut permeability may be an effective new treatment model.
“Our findings suggest that the intestinal lining is a therapeutic target,” says Mauri. “Importantly, we found that using existing drugs that restore the gut-barrier integrity i.e., prevent the gut from becoming leaky or inhibit inflammatory cells from moving to and from to the gut, could reduce the severity of arthritis in pre-clinical models.”
The new study was published in the journal Med.
Source: University College London
