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P399. Oral butyrate plus inulin improve serum metabolomic profile and gut microbiota composition in ulcerative colitis and celiac disease

S. Sitkin1,2, E. Tkachenko2, T. Vakhitov1, L. Oreshko2, T. Zhigalova2, 1State Research Institute of Highly Pure Biopreparations, Dept. of Applied Microbiology, St. Petersburg, Russian Federation, 2North-Western State Medical University named after I.I. Mechnikov, Dept. of Propaedeutics of Internal Diseases, St. Petersburg, Russian Federation

Background

Intestinal microbiota is most probably involved in the development and maintenance of autoimmune inflammation in ulcerative colitis (UC) and celiac disease (CD). Gas chromatography-mass spectrometry (GC-MS) of serum generates comprehensive metabolic profiles, reflecting integrated human and gut microbial metabolism which may be altered in disease states.

We aimed to investigate the effects of an orally administered butyrate plus inulin on GC-MS-based serum metabolomic profiles and gut (fecal) microbiota composition in UC patients, CD patients and healthy controls (HC).

Methods

Serum metabolomic profiles and fecal samples were collected from 75 individuals: 20 patients with mild–moderate active UC, 35 CD patients, and 20 healthy controls. ROC curve analysis, some multivariate analysis techniques such as principal components analysis (PCA) were used to identify of biomarkers and to assess differences between groups. The quantitative real-time polymerase chain reaction (qRT-PCR) was used for quantitative fecal microbiota assessment.

Results

We characterized 84 serum metabolites to differentiate between UC, CD and HC cohorts. 18 metabolites at least have a combined (human plus 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.

Differences in serum metabolite levels of UC patients, CD patients and controls may indicate the difference in the metabolic activity of gut microbiota (Clostridia and Bacteroides spp.) involved in phenylalanine and tyrosine metabolism. Increased serum levels of succinic acid, produced abundantly by some Bacteroides spp., suggest its possible damaging effect on intestinal mucosa especially in UC.

Orally administered butyrate plus inulin (Zacofalk NMX, Dr. Falk Pharma GmbH, 3 tablets per day for 4 weeks) as supplement to mesalazine in UC or gluten free diet (GFD) in CD was effective in reducing disease activity with a marked improvement of serum metabolomic profiles (including succinic acid reduction) and gut microbiota (including reduction of Bacteroides fragilis/Faecali-bacterium prausnitzii ratio and butyrate-producing bacteria increase) in both conditions. There were no any adverse events.

Conclusion

Oral butyrate plus inulin can be effectively used in UC, as well as in CD, improving symptoms, serum metabolomic profile and gut microbiota composition. Quantitative metabolomic profiling of serum using GC-MS discriminates between UC patients, CD patients and healthy controls.