A team from the Pasteur Institute of France today in PNAS shows that the protein PPAR-gamma is associated with protection against inflammatory bowel diseases like Crohn’s disease.
Restore the natural barriers to intestinal infections through diet and pharmacological intervention can be a therapeutic option in cases of intestinal diseases like Crohn’s disease. This is according to a study published today in Proceedings of the National Academy of Sciences, conducted by a team from the Pasteur Institute of Lille, France. Mathias Chamaillard is the lead author.
The work’s protagonist is the role of the protein PPAR-gamma, regulator of antimicrobial peptides in the gut. The authors sought to determine whether this protein could act as protective against Crohn’s disease and other inflammatory conditions, and found in mouse model genetically engineered to be deficient in PPAR-gamma, there was a clearly reduced ability to fight infection bacteria in the colon compared with control models.
Reduced expression
In addition, researchers have found that colon biopsies of human specimens diagnosed with Crohn’s disease also have significantly reduced expression of antimicrobial peptides regulated by this protein.
Faced with these data, Chamaillard and his team suggest that both nutritional regimes such as certain drugs might improve the rehabilitation of dependent antimicrobial barriers PPAR-gamma in the gastrointestinal tract. This approach would help in the prevention of chronic injuries related to the onset of the disease.
The work is based on the leading role that has PPAR-gamma in intestinal homeostasis. It has been shown to act as an antimicrobial factor by maintaining the epithelial expression of beta-defensins colonies in the colon (from mDefB10 DEFB1 in mice and humans.)
Researchers have observed that the colonic mucosa of animals mutant for PPAR-gamma eliminates some of the main components of the intestinal microbiota, such as Candida albicans, Bacteroides fragilis, Enterococcus faecalis and Escherichia coli. As described, the neutralization of colonic activity, using an antibody anti-mDefB10 blocker, is effective in systems dependent on PPAR-gamma.
Also reveal the presence of a functional promoter variant required for the expression of DEFB1, which gives special protection against Crohn’s disease. This information has allowed the authors point out that the relationship with the disease of the colon is specifically linked to reduced expression DEFB1, irrespective of inflammation.