Advantages
- Low side effect risks due to the supplementation of intestinal metabolite/bacteria.
- New prevention/treatment concept to be used in combination with existing drugs.
Technology Overview & Background
Ulcerative colitis (UC) is a chronic inflammation from the colon to the rectum, triggered by dietary changes and other factors, where the immune system fails to function properly, resulting in the production of inflammatory cytokines. Although several classes of medication have been developed, only about 50% of patients respond to them, and many patients still suffer from symptoms with repeated remissions and exacerbations.
The research group of Prof. Kazuyo Moro, known for the discoverer of type 2 innate lymphocytes (ILC2), has found that changes in intestinal flora caused by appendectomy alleviate the symptoms of UC with improvement of intestinal epithelial barrier function by enhanced mucin production through tuft cell > ILC2 > goblet cell activation cascade.
They identified 11-hydroxy-eicosapentaenoic acid (11-HEPE), a metabolite of eicosapentaenoic acid (EPA), as the molecule contributing to tuft cell activation/augmentation. The bacteria that enzymatically convert EPA to 11-HEPE via 11-LOX enzyme were also identified. 11-HEPE and 11-LOX expressing bacteria are expected to be applicable for the prevention, remission maintenance, and potentially treatment of UC, as well as other symptoms of inflammatory bowel disease (IBD), Crohn’s disease and unclassified IBD.
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Data
- An observed increase in the number of tuft cells in intestinal epithelial tissue in humans who have undergone an appendicectomy and patients in UC remission. Intestinal tuft cells reportedly decrease in UC patients.
- In a dextran sulfate sodium (DSS) induced UC mouse model, enteral administration of 11-HEPE 7, 5, 3 and 1 day before the start of DSS drinking alleviated weight loss and colon shortening on day 8.
- 11-HEPE increased tuft cells and mucin secretion in mice.
- Identified intestinal bacteria that metabolize EPA to 11-HEPE.
Patent(s)
Patent pending (not published)
Researchers & Academic Institution
Professor Kazuyo Moro, PhD (Osaka University Graduate School of Medicine, Japan)
Expectations
- We are seeking pharmaceutical/supplement companies interested in developing 11-HEPE and its derivatives as therapeutic/prophylactic agent, and/or 11-HEPE producing bacteria as probiotics for IBD.
- Collaborative research is also welcome.
- Details can be disclosed under CDA.
- We can also arrange a non-confidential meeting with the inventors.
Project.KJ-04988