Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study postulates that altered microbiota associated with areas of mucosal inflammation in CD, can be characterized by an increased proteolytic profile. This is clinically important as it may be possible to modulate the proteolytic activity of the CD-associated bacteria by using other bacteria that produce protease inhibitors, such as serpins.
Crohn's disease (CD), characterized by discontinuous intestinal injury and inflammation, has been associated with changes in the luminal microbiota and impaired barrier function. Previously, the investigators have shown that in patients with CD, the mucosa-associated microbiota is altered. Additionally, it has been shown that in patients with active CD, areas of intestinal injury are associated with impaired barrier function, but the mechanisms remain unclear. Increased host proteolytic activity has been reported in both CD and ulcerative colitis (UC). The microbiota is an important source of proteases with potential inflammatory and barrier disrupting capacity. Indeed, preliminary data indicate that in UC patients the gut microbiota contributes to proteolytic imbalance. It is unknown whether this is also the case in CD. Specifically, this study postulates that the altered microbiota associated with areas of mucosal inflammation in CD, is characterized by an increased proteolytic profile. This is clinically important as it may be possible to modulate the proteolytic activity of the CD-associated bacteria by using other bacteria that produce protease inhibitors such as serpins.
In this prospective observational study, patients booked for routine white light colonoscopy under the care of the Division of Gastroenterology, Hamilton Health Sciences at the McMaster University Medical Centre and Juravinski Hospital Endoscopy Units will be invited to participate. Patients previously diagnosed with Crohn's disease who have a clinical indication for undergoing a standard white light colonoscopy, as determined by the gastroenterologist, will be invited to participate; biopsy samples and mucosal brushings will be taken from inflamed and non-inflamed areas in the ileum or colon.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Crohn's disease | Patients previously diagnosed with Crohn's disease who have a clinical indication for undergoing a standard white light colonoscopy, as determined by their gastroenterologist, will be invited to participate. Patients undergoing colonoscopy for other indications (for example, for the investigation of possible malignancy, polyps, gastrointestinal bleeding or diarrhea, without colonic inflammation), will not be included in this study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Colonoscopy | Procedure | Colonoscopy with video recording and biopsy collection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Altered microbiota associated with areas of mucosal inflammation in CD, is characterized by an increased proteolytic profile | Increase proteolytic activity profile influenced by microbiota composition in inflamed areas comprared with non-inflamed areas in a context of Crohn's disease | December 2019 - January 2025 |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Study subjects will be invited to participate in the outpatient clinic if the clinical need for standard, white light colonoscopy has already been confirmed as well as a previous diagnosis of Crohn's disease. All study subjects will be enrolled into the study after informed consent
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| McMaster University | Hamilton | Ontario | L8N 3Z5 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17653185 | Background | Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007 Jul 26;448(7152):427-34. doi: 10.1038/nature06005. | |
| 12876555 | Background | Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003 Jul;3(7):521-33. doi: 10.1038/nri1132. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D003113 | Colonoscopy |
| ID | Term |
|---|---|
| D016099 | Endoscopy, Gastrointestinal |
| D016145 | Endoscopy, Digestive System |
| D003938 | Diagnostic Techniques, Digestive System |
| D019937 | Diagnostic Techniques and Procedures |
Not provided
Not provided
Not provided
Not provided
Not provided
| 29848021 | Background | Libertucci J, Dutta U, Kaur S, Jury J, Rossi L, Fontes ME, Shajib MS, Khan WI, Surette MG, Verdu EF, Armstrong D. Inflammation-related differences in mucosa-associated microbiota and intestinal barrier function in colonic Crohn's disease. Am J Physiol Gastrointest Liver Physiol. 2018 Sep 1;315(3):G420-G431. doi: 10.1152/ajpgi.00411.2017. Epub 2018 May 31. |
| 29777136 | Background | Denadai-Souza A, Bonnart C, Tapias NS, Marcellin M, Gilmore B, Alric L, Bonnet D, Burlet-Schiltz O, Hollenberg MD, Vergnolle N, Deraison C. Functional Proteomic Profiling of Secreted Serine Proteases in Health and Inflammatory Bowel Disease. Sci Rep. 2018 May 18;8(1):7834. doi: 10.1038/s41598-018-26282-y. |
| 27196587 | Background | Vergnolle N. Protease inhibition as new therapeutic strategy for GI diseases. Gut. 2016 Jul;65(7):1215-24. doi: 10.1136/gutjnl-2015-309147. Epub 2016 Apr 12. |
| 21199654 | Background | Motta JP, Magne L, Descamps D, Rolland C, Squarzoni-Dale C, Rousset P, Martin L, Cenac N, Balloy V, Huerre M, Frohlich LF, Jenne D, Wartelle J, Belaaouaj A, Mas E, Vinel JP, Alric L, Chignard M, Vergnolle N, Sallenave JM. Modifying the protease, antiprotease pattern by elafin overexpression protects mice from colitis. Gastroenterology. 2011 Apr;140(4):1272-82. doi: 10.1053/j.gastro.2010.12.050. Epub 2011 Jan 1. |
| 30867416 | Background | Caminero A, McCarville JL, Galipeau HJ, Deraison C, Bernier SP, Constante M, Rolland C, Meisel M, Murray JA, Yu XB, Alaedini A, Coombes BK, Bercik P, Southward CM, Ruf W, Jabri B, Chirdo FG, Casqueiro J, Surette MG, Vergnolle N, Verdu EF. Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2. Nat Commun. 2019 Mar 13;10(1):1198. doi: 10.1038/s41467-019-09037-9. |
| D007410 | Intestinal Diseases |
| D003933 | Diagnosis |
| D004724 | Endoscopy |
| D003949 | Diagnostic Techniques, Surgical |
| D013505 | Digestive System Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D019060 | Minimally Invasive Surgical Procedures |