September 1, 2022
Crohn’s Disease and the Human Microbiome
Crohn’s Disease is a debilitating chronic disease that falls under the umbrella of inflammatory bowel disease (IBD or IBS), a host of conditions affecting an estimated 3 million Americans.
Given the proximity of gut and fecal microorganisms to the tissue types affected by Crohn’s Disease, it may seem strange that the role of these microbiota have not been thoroughly investigated. However, authors of a paper published yesterday in Cell Host and Microbiome looked for the first time at the effects of a bacterial enzyme called DL-endopeptidase on Crohn’s Disease with exciting results.
Genomic Analysis Identifies a Depleted Bacterial Enzyme
In a metagenomic analysis of 857 patients, the authors found that genes for the bacterial enzyme DL-endopeptidase were decreased in Crohn’s Disease patients and their absence negatively correlated with colitis, another form of IBD.
The authors also observed this effect experimentally: mice treated with fecal microorganisms from Crohn’s Disease patients with low DL-endopeptidase activity were predisposed to developing colitis.
Restoring DL-endopeptidase Improves CD via NOD2
So what could be the mechanism for DL-endopeptidase affecting Crohn’s Disease and colitis? The answer is the NOD2 receptor, a well-established player in Crohn’s Disease. Loss of function mutations in NOD2 are commonly associated with the disease.
What the authors found is that treatment with DL-endopeptidase increased the amount of NOD2 ligands (molecule that bind to NOD2), restoring function of that signaling pathway and significantly improving Crohn’s Disease and colitis outcomes in mouse models. These results identify NOD2 and DL-endopeptidase as promising targets for therapeutic development in treating Crohn’s Disease, colitis and IBD generally.
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Jane Cook, Journalist & Content Writer, Bridge Informatics
Jane is a Content Writer at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email daniel.dacey@old.bridgeinformatics.com or dan.ryder@old.bridgeinformatics.com.
Sources:
https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(22)00395-X
https://www.mayoclinicproceedings.org/article/S0025-6196(17)30313-0/fulltext#:~:text=Crohn%20disease%20is%20a%20chronic%20disease%20with%20an%20annual%20incidence,to%2020%20cases%20per%20100%2C000
