An Unexplored Role for MMP-7 (Matrix Metalloproteinase-7) in Promoting Gut Permeability After Ischemic Stroke
Jonathan Larochelle1, Changjun Yang1, Lei Liu1
1Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville.
Abstract:
Poststroke infections are common complications of stroke and are highly associated with poor outcomes for patients. Stroke induces profound immunodepression coupled with alterations to autonomic signaling, which together render the body more susceptible to infection from without (nosocomial/community-acquired infection) and from within (commensal bacterial infection). Critical to the hypothesis of commensal infection is the phenomenon of poststroke gut permeability and gut dysbiosis. Few studies have provided adequate explanations for the mechanisms underlying the molecular alterations that produce a more permeable gut and perturbed gut microbiota after stroke. A dysregulation in the production of matrix MMP-7 (metalloproteinase-7) may play a critical role in the progression of gut permeability after stroke. By cleaving junctional and extracellular matrix proteins, MMP-7 is capable of compromising gut barrier integrity. Because of MMP-7's unique abundance in the small intestine and its capacity to be induced in states of bacterial invasion and inflammation, along with its unique degradative capability, MMP-7 may be crucially important to the progression of gut permeability after ischemic stroke.
Insights
Stroke survivors often develop infections due to immune depression and gut changes. Matrix metalloproteinase-7 (MMP-7) may increase gut permeability after stroke, worsening these complications.
Area of Science:
- Neuroscience
- Immunology
- Gastroenterology
Background:
- Poststroke infections are common and linked to poor patient outcomes.
- Stroke causes immune suppression and autonomic signaling changes, increasing infection susceptibility.
- Gut permeability and dysbiosis are implicated in poststroke commensal infections.
Purpose of the Study:
- To investigate the molecular mechanisms behind increased gut permeability after stroke.
- To explore the role of matrix metalloproteinase-7 (MMP-7) in poststroke gut barrier dysfunction.
Main Methods:
- The study focuses on the molecular mechanisms of gut permeability post-stroke.
- It examines the potential role of matrix metalloproteinase-7 (MMP-7) in compromising gut barrier integrity.
Main Results:
- Stroke-induced immunodepression and altered autonomic signaling increase infection risk.
- Dysregulation of MMP-7 production may be a key factor in developing poststroke gut permeability.
- MMP-7 cleaves proteins, compromising gut barrier integrity, especially in the small intestine.
Conclusions:
- MMP-7 dysregulation is a potential critical factor in poststroke gut permeability.
- Understanding MMP-7's role could lead to new therapeutic strategies for poststroke complications.


