SERUM METABOLOME BY GAS CHROMATOGRAPHY-MASS SPECTROMETRY (GC-MS) IN ULCERATIVE COLITIS AND CELIAC DISEASE
Metabolomics is the emerging science of measurement and analysis of metabolome - the complete set of low molecular weight compounds in a cell, tissue, organ or whole organism. One of the aims of metabolomics is to research the response of an organism to a pathophysiological insult by measuring the concentrations of small molecule metabolites in biofluids and tissues and its dynamics. Intestinal microbiota is most probably involved in the development and maintenance of autoimmune inflammation in ulcerative colitis and celiac disease. Gas chromatography-mass spectrometry (GC - MS) of serum generates comprehensive metabolic profiles, reflecting integrated human (systemic) and gut microbial metabolism which may be altered in disease states. The aim of this study was to investigate GC - MS-based serum metabolomic profiles in UC and CD patients. Serum metabolic profiles were collected from 75 individuals: 20 patients with mild-moderate active UC, 35 CD patients, and 20 healthy controls (HC). We characterized 84 serum metabolites by use GC - MS. 18 metabolites at least have a combined (human + microbial) origin. In serum of UC patients, phenylacetic acid (PAA), 4-hydroxyphenylacetic acid (4-HPAA), 3-indolylacetic acid (IAA), succinic acid (SA) and fumaric acid (FA) were the metabolites most prominently increased, whereas 3-phenylpropionic acid (PPA) was significantly decreased. Serum of CD patients showed significant increases in IAA, 3-indolepropionic acid (IPA), SA and FA. Increased serum levels of succinic acid suggest its possible damaging effect on intestinal mucosa especially in ulcerative colitis. Orally administered butyrate + inulin as supplement to mesalazine in UC or gluten free diet in CD was effective in reducing disease activity with a marked improvement of serum metabolomic profiles (including SA reduction) and gut microbiota in both diseases. There were no any adverse events.