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The aetiology of pouchitis remains poorly understood. The aim of this study was to determine whether patients with pouchitis have different plasma metaboliteprofiles to patients with unaffected pouches.We used a non-targeted metabonomic approach, combining 600 MHzproton nuclear magnetic resonance spectroscopy (1H-NMR) with pattern recognition methods (principal component analysis and orthogonalprojections to latent structures) to analyse plasma metaboliteprofiles in 16 patients with and 13 without pouchitis following restorativeproctocolectomy for ulcerative colitis. Disease severity was determined using the pouch disease activity index (PDAI). Metabolite levels were compared using the Mann-Whitney U test.Patients with pouchitis had significantly higher PDAI scores than healthy controls (median 11 [range 7-15] vs 0 [0-4], P < 0.0001). The main differentiating metabolite was a1-acid glycoprotein (orosomucoid), (δ 2.04 and 2.08 parts per million). This waspresent in higher concentrations in the pouchitis group (median 4.35 [range 4.01-4.87] vs 4.21 [3.65-4.42] arbitrary units, P = 0.004). An associated rise in plasma interleukin-6 was demonstrated (median 3.89 [range 0.00-14.42] vs 1.64 [0.42-5.96] pg/ml, P = 0.023).Raised plasma α1-acid glycoprotein and interleukin-6 in pouchitis has not beenpreviously described. It is not known whether this is aprimary event that maypredispose to the development of pouchitis or a consequence of already established inflammation.