Metabolite biomarkers to distinguish Crohn's disease from ulcerative colitis and methods using the same
View Patent ↗The present invention provides various biomarkers of inflammatory bowel disease, including biomarkers for Crohn's disease and biomarkers for Ulcerative colitis. The present invention also provides various methods of using the biomarkers, including methods for diagnosis of inflammatory bowel disease, methods for distinguishing between inflammatory bowel diseases, methods of determining predisposition to inflammatory bowel disease, methods of monitoring progression/regression of inflammatory bowel disease, methods of assessing efficacy of compositions for treating inflammatory bowel disease, methods of screening compositions for activity in modulating biomarkers of inflammatory bowel disease, methods of treating inflammatory bowel disease, as well as other methods based on biomarkers of inflammatory bowel disease.
1. A method of distinguishing Crohn's disease from Ulcerative colitis in a subject, comprising
analyzing a biological sample from a subject to determine the level(s) of one or more biomarkers for inflammatory bowel disease in the sample, wherein the one or more biomarkers are selected from the group consisting of 6-beta-OH-lithocholate, 7-alpha-hydroxy-3-oxo-4-cholestenoate (7-HOCA), Deoxycholic acid, Glycodeoxycholic acid, and Hyodeoxycholic acid; and
comparing the level(s) of the one or more biomarkers in the sample to Crohn's disease-positive reference levels that distinguish over Ulcerative colitis and/or to Ulcerative Colitis-positive reference levels that distinguish over Crohn's disease in order to determine whether the subject has Crohn's disease or Ulcerative colitis.
2. The method of claim 1 , further comprising analyzing a biological sample from a subject to determine the level(s) of one or more additional biomarkers for inflammatory bowel disease in the sample, wherein the one or more additional biomarkers are selected from the group consisting of lathosterol, hippurate, taurodeoxycholate, indoleacetate, cotinine, urea, 2-palmitoylglycerophosphoethanolamine, cholesterol, taurolithocholate 3-sulfate, p-cresol sulfate, 3-indolepropionate, chenodeoxycholate, 7-ketolithocholate, phosphate, dimethylarginine, ornithine, pyroglutamylglycine, 1,5-anhydroglucitol (1,5-AG), caproate (6:0), taurochenodeoxycholate, 3-phenylpropionate (hydrocinnamate), glycerophosphorylcholine (GPC), heptanoate (7:0), dehydroisoandrosterone sulfate (DHEA-S), sebacate, erythronate, benzoate, glycylvaline, mannitol, N-acetylornithine, taurocholate, bradykinin, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF), suberate, malate, 2-hydroxyhippurate (salicylurate), acetylphosphate, glycocholate, stachydrine, pentadecanoate (15:0), xanthine, beta-hydroxyisovalerate, and gamma-tocopherol.
3. The method of claim 1 , wherein the sample is analyzed using one or more techniques selected from the group consisting of mass spectrometry, ELISA, and antibody linkage.
4. The method of claim 1 , wherein the biological sample is a plasma sample.