P852 A metabolomics approach to discover biomarkers of chronic intestinal inflammation associated with gut microbiota dysbiosis in ulcerative colitis and Celiac Disease

• Published in: Journal of Crohn's and colitis 2018-01, Vol.12 (supplement_1), p.S547-S548
• Main Authors: Sitkin, S, Vakhitov, T, Tkachenko, E, Avalueva, E, Oreshko, L, Zhigalova, T, Demyanova, E, Shalaeva, O, Utsal, V, Suvorova, M, Komlichenko, E
• Format: Article
• Language: English
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjx180.979

Abstract Background The effect of gut microbiota dysbiosis on human metabolome and the potential of microbial and endogenous metabolites as biomarkers of chronic intestinal inflammation (CII) are not clear. Methods Forty ulcerative colitis (UC) patients, 43 celiac disease (CD) patients and 42 healthy volunteers (HV) were enrolled. The qRT-PCR was used for fecal microbiota assessment. Serum metabolomic assays were conducted using the GC-MS. UC patients were randomised into A1 and A2 groups and CD patients were randomised into B1 and B2 groups. A1 and B1 groups received oral calcium butyrate plus inulin for 28 days as supplement to oral mesalazine in UC or gluten-free diet (GFD) in CD. A2 and B2 groups received standard treatment or GFD. Results Butyrate-producing bacteria (BPB) were depleted in UC compared with HV. CD patients had lower Bifidobacterium spp. counts than HV or UC. Taxonomic dysbiosis in both UC and CD was characterised by a higher Bacteroides fragilis/Faecalibacterium prausnitzii ratio compared with HV. Significant changes in gut microbiota in both UC and CD were accompanied by changes in serum microbial metabolites levels. In UC serum lactic acid, 2-hydroxybutyric acid (2-HBA), 3-hydroxyisobutyric acid (3-HIBA), 2-hydroxyisovaleric acid (2-HIVA), 3-hydroxycinnamic acid, succinic acid (SA), benzoic acid (BA) and 4-hydroxyphenylacetic acid (4-HPAA) levels were significantly increased compared with HV. Serum levels of caproic acid, linoleic acid (LA) and eicosadienoic acid (EDA) in UC were significantly lower than in HV. Serum of CD patients showed significant increases in stearic acid (StA), 2-HIVA, SA, fumaric acid and BA compared with HV. De novo lipogenesis index (DNL) (C16:0/C18:2n-6) was significantly elevated in UC compared with both HV and CD. The ELOVL6 elongase activity index (C18:0/C16:0) and the StA/lA ratio (C18:0/C18:2n-6) in UC were significantly increased compared with HV. AA/EDA ratio (C20:4n-6/C20:2n-6) was increased in both UC and CD. Oral butyrate plus inulin significantly enhanced fecal BPB, reduced elevated B. fragilis/F. prausnitzii ratio, lowered serum pro-inflammatory SA and 2-HIVA and restored the initially lowered LA and EDA. 85% of UC patients in A1 (butyrate) group demonstrated significant improvement in rectal bleeding and stool frequency by day 14, compared with 55% in A2 group. Conclusions The changes in serum metabolome, reflecting metabolic pathways disturbances (glycolysis, TCA cycle, fatty acid metabolism, ke