Intestinal diseases affect nearly 250,000 people in France, and offer little hope of treatment. But a new study reveals promising results for some of these pathologies.
Some intestinal diseases, including Crohn's disease and ulcerative colitis, are associated with a decrease in antibodies vital to the mucosal barrier. Researchers from the Cleveland Clinic discovered a bacteria that could be the cause of this insufficient rate. "Identifying this bacteria is the first step towards developing new treatments," scientists say. Their results were published in the prestigious journal Scientists are able to explain the origins of science.
Vital antibodies for the mucosal barrier
In the intestines, there is an antibody essential to the integrity of the mucosal barrier: secretory immunoglobulin A (IgA). “It binds to commensal and pathogenic microorganisms to prevent adhesion and infection,” "said Qiuhe Lu, the study's first author, in an interview with Science and Future. In chronic inflammatory bowel diseases, the Crohn's disease and ulcerative colitis, it is precisely the level of this secretory immunoglobulin A which is abnormally low, which can lead to an increased risk of infection and excessive inflammation.
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"Previous work has highlighted defense mechanisms of certain pathogens against this antibody: they degrade IgA in order to escape the immune system," he adds. In a new study, Qiuhe Lu's team identifies a new commensal bacterium, called Tomasiella immunophila, and found that it affects the production of this immunoglobulin.
What is a commensal bacteria? Commensalism is a type of association between two organisms, such as parasitism or symbiosis. It refers to an association that is beneficial to one organism and harmless to the other.
Tomasiella immunophila, a new bacteria that degrades these antibodies
“ We identified a bacterium that had never been reported before this study," Qiuhe Li is elated. Scientists sought to identify commensal bacteria that could degrade IgA. Using a technique called "functional screening," they screened thousands of bacteria and eventually isolated an unknown strain that degrades secretory immunoglobulin A. We named it Tomasiella immunophila."
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But how does it affect antibodies? Several hypotheses are put forward by scientists. Furthermore, T. immunophila might use IgA as a nutrient source, since IgA is one of the most abundant proteins in the intestinal lumen, i.e., in the pit of the intestinal tube," suggests the researcher.
In addition, the researchers revealed another mechanism by which the bacterium can influence the level of IgA in the intestines. The bacterium transports several enzymes, substances capable of catalyzing chemical reactions, to its outer membrane, where they are packaged in vesicles. This encapsulation improves the stability of the enzymes compared to their free form and allows them to circulate in the intestinal lumen. In particular, one of the enzymes contained in these vesicles is capable of degrading IgA.
A promising lead for possible treatments against Crohn's disease
“ Identifying the culprit behind the breakdown of the intestinal barrier is an important step toward developing much-needed therapies for conditions such as inflammatory bowel disease, Crohn's disease and ulcerative colitis," enthuses Thaddeus Stappenbeck, co-author of the study.
And researchers already have encouraging leads to make this bacteria a new therapeutic target. We know that certain inhibitors can prevent Tomasiella immunophila from degrading IgA," "Further studies will be needed to deepen the understanding of this mechanism," says Qiuhe Lu.
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