Crohn's Disease - Inflammation and Microbial Proteolytic Activity

Investigating the Relationship Between Inflammation and Proteolytic Activity From Mucosa-associated Microbiota in Crohn's Disease Patients

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.

Inclusion Criteria:

• Be aged between 18 - 70 years old
• Have a confirmed diagnosis of Crohn's disease
• Have a clinical indication for standard, white light colonoscopy to assess disease activity and extent

Exclusion Criteria:

• Inability to provide written informed consent
• Presence of serious life-threatening co-morbidities
• Evidence of toxic megacolon, jaundice, cirrhosis, renal dysfunction, acute GI bleeding
• History of difficult colonoscopy, strictures or extensive diverticulosis
• Antibiotics in the last month
• Probiotics in the last week