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Altered colonic mucosal polyunsaturated fatty acid (PUFA) derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology

Altered colonic mucosal polyunsaturated fatty acid (PUFA) derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology
Altered colonic mucosal polyunsaturated fatty acid (PUFA) derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology
OBJECTIVES: 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.

DESIGN: 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.
1932-6203
e76532
Masoodi, Mojgan
57584d36-e8d2-4c66-8e23-8bfa41be2382
Pearl, Daniel S.
ce519b8f-c597-4d53-942c-9e35b1cf798a
Eiden, Michael
3c187263-201a-4e0c-8803-29848a1ead83
Shute, Janis K.
a5eef853-50ae-4abf-9e34-1c873601437f
Brown, James F.
f4e87e15-d5ce-4b1a-91ef-7dc92dc6dbea
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Trebble, Timothy M.
48119242-d090-4778-afd9-58f451dbeecf
Masoodi, Mojgan
57584d36-e8d2-4c66-8e23-8bfa41be2382
Pearl, Daniel S.
ce519b8f-c597-4d53-942c-9e35b1cf798a
Eiden, Michael
3c187263-201a-4e0c-8803-29848a1ead83
Shute, Janis K.
a5eef853-50ae-4abf-9e34-1c873601437f
Brown, James F.
f4e87e15-d5ce-4b1a-91ef-7dc92dc6dbea
Calder, Philip C.
1797e54f-378e-4dcb-80a4-3e30018f07a6
Trebble, Timothy M.
48119242-d090-4778-afd9-58f451dbeecf

Masoodi, Mojgan, Pearl, Daniel S., Eiden, Michael, Shute, Janis K., Brown, James F., Calder, Philip C. and Trebble, Timothy M. (2013) Altered colonic mucosal polyunsaturated fatty acid (PUFA) derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology. PLoS ONE, 8 (10), e76532. (doi:10.1371/journal.pone.0076532). (PMID:24204637)

Record type: Article

Abstract

OBJECTIVES: 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.

DESIGN: 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.

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Published date: 18 October 2013
Organisations: Human Development & Health

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Local EPrints ID: 359822
URI: http://eprints.soton.ac.uk/id/eprint/359822
ISSN: 1932-6203
PURE UUID: 353c546f-3e25-4d4b-87e1-a92bcab06c62
ORCID for Philip C. Calder: ORCID iD orcid.org/0000-0002-6038-710X

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Date deposited: 14 Nov 2013 13:25
Last modified: 28 Oct 2023 01:39

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Contributors

Author: Mojgan Masoodi
Author: Daniel S. Pearl
Author: Michael Eiden
Author: Janis K. Shute
Author: James F. Brown
Author: Timothy M. Trebble

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