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* = Presenting author

P711 Metabolic dysbiosis concept and its biomarkers in ulcerative colitis and celiac disease

S. Sitkin*1, 2, T. Vakhitov1, E. Tkachenko2, 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

Specific features of intestinal dysbiosis in UC may include an increased proportion of Actinobacteria and Proteobacteria. Furthermore UC patients show an increase of Enterococcus and Fusobacterium varium, a loss of butyrate-producing bacteria (BPB) and a decrease in Akkermansia muciniphila.

CD patients show a significantly reduced Gram-positive to Gram-negative bacteria ratio, a loss of Bifidobacterium, Clostridium histolyticum, C. lituseburense and Faecalibacterium prausnitzii, an increase of Bacteroides-Prevotella group and an increased abundance of Bacteroides fragilis.

Such changes we call the "microbiological" dysbiosis, unlike "metabolic" dysbiosis (a novel term that we introduce) that is primarily characterized by metabolic abnormalities (e.g. serum, urinary or fecal) in the host due to changes in intestinal microbial metabolism. Metabolic dysbiosis is not necessarily accompanied by appreciable quantitative and/or qualitative changes in microbiota composition.

We aimed to identify the signs of intestinal dysbiosis (both microbiological and metabolic) in patients with UC and CD.

Methods

Serum metabolomic profiles and fecal samples were collected from 24 patients with mild-moderate active UC, 37 CD patients, and 28 healthy controls (HC).

Gas chromatography-mass spectrometry (GC-MS) to determine serum metabolomic profiles and quantitative real-time PCR (qRT-PCR) to assess of fecal microbiota composition were used.

Results

We found signs of both types of dysbiosis in UC and CD patients. Microbiological dysbiosis in UC and CD was characterized by a higher ratio of Bacteroides fragilis to Faecalibacterium prausnitzii and depletion of butyrate-producing bacteria. The degree of change differed between UC and CD groups. There was no significant difference in the abundance of individual species between groups.

Metabolic dysbiosis in both disorders is characterized by significant changes in serum organic acids of a 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 most prominently increased, whereas 3-phenylpropionic acid (PPA) was significantly decreased. Serum of CD patients showed significant increases in IAA, 3-indolepropionic acid (IPA), benzoic acid (BA), SA and FA.

Oral butyrate plus inulin was effective in an improvement of symptoms, serum metabolomic profiles and gut microbiota in both conditions.

Conclusion

An increased ratio of B. fragilis to F. prausnitzii and a decrease of BPB may be available biomarkers for intestinal dysbiosis in UC and CD.

Metabolic dysbiosis in UC and CD is characterized by changes in serum organic acids. Some of them may be useful biomarkers of chronic intestinal inflammation.