title: Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA) derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology.
abstract: OBJECTIVE
  Ulcerative colitis (UC) is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA)) are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX) inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids) within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC.
  
  
  METHODS
  Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically.
  
  
  RESULTS
  Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems.
  
  
  CONCLUSIONS
  Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile.
authors.affiliation: Nestlé Institute of Health Sciences, Lausanne, Switzerland ; Medical Research Council, Cambridge, Cambridgeshire, United Kingdom ; Department of Nutritional Sciences, University of Toronto, Ontario, Canada.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Masoodi
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pearl
authors.forename: Michael
authors.initials: M
authors.lastname: Eiden
authors.forename: Janis K
authors.initials: JK
authors.lastname: Shute
authors.forename: James F
authors.initials: JF
authors.lastname: Brown
authors.forename: Philip C
authors.initials: PC
authors.lastname: Calder
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Trebble
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000636:Aminosalicylic Acids / Q000627:therapeutic use; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000737:chemistry / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D000636:Aminosalicylic Acids; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases