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Treatment of Insulin-Resistant Modulation of Gut Immunity and Intestinal Epithelial Function

Technology Application
Metabolic disease managementControl of glucose levels Immunotherapythrough improvement of oral tolerance
Detailed Technology Description
New use of 5-ASA for glucose management
*Abstract

Management of obesity and associated metabolicabnormalities requires new and efficient approaches. Researchers at UHN havedeveloped a new method of management of glucose levels which utilizes 5-ASA. Ithas been shown that 5-ASA has an anti-inflammatory effect on the gut immunecell population in the colon and small bowel of mice fed a high-fat diet. Thetendency for obese patients to have increasedlevels of inflammatory immune cells including Tbet+, CD4+ and CD8+ T cells aswell as a reduction of Tregs in the intestine, creates an opportunity for the developmentof new anti-inflammatory formulations based on 5-ASA.


The research team fromUHN has also shown that treatment with 5-ASA did not produce weight change inanimal models while resulting in significant improvements in glucose toleranceand insulin sensitivity. In addition, 5-ASA treatment also improved gutmicrobial parameters, including bacterial diversity and enrichment of selectshort-chain fatty acid producers, intestinal permeability, and demonstrated oraltolerance in mice.


The overall result was a reduction in systemic inflammationof metabolic tissues and improved glucose homeostasis. 5-ASA may representfirst-line gut-specific immunomodulatory therapy for obesity-associatedmetabolic abnormalities.


*Principal Investigator

Dr. Daniel Winer,University Health Network (lead researcher)

*Publications
Winer DA et al. Regulationof obesity-related insulin resistance with gut anti-inflammatory agents. Cell Metabolism 21, 527–542,April 7, 2015
Country/Region
USA

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