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P369. Dysbiosis in inflammatory bowel disease: A link with antimicrobial peptides secretion?

S. Rajca1, H. Duboc1, H. Sokol1, L. Humbert1, V. Grondin1, G. Thomas1, C. Bridonneau2, P. Langella2, C. Mayeur2, L. Beaugerie1, J. Cosnes1, J. Masliah1, D. Rainteau1, P. Seksik1

1Saint Antoine's Hospital, Paris, France; 2INRA, Jouy-en-Josas, France

Aim: Alterations of intestinal microbiota (dysbiosis) are involved in inflammatory bowel diseases (IBD) pathogenesis. Antimicrobial peptides (AMP) such as defensins play a pivotal role in the regulation of the intestinal microbiota. It has been also shown that microbiota participates in AMP secretion giving a picture of a regulation loop. Besides, defensins deficiency (mRNA, immunohistochemistry), has been incriminated in IBD pathogenesis. More precisely, the deficiency implied human beta-defensin 1 (hBD1) in IBD and alpha-defensin 5 (HD5) in ileal Crohn's disease. The aim of our study was to look for a link between IBD associated dysbiosis and gut intraluminal expression of hBD1 and HD5 human defensins.

Materials and Methods: Faecal samples were collected from 31 healthy subjects and 41 patients with colonic IBD including 12 patients with Crohn's disease, 29 with ulcerative colitis and among them 18 were in remission and 23 with active disease. Exclusion criteria were the use of antibiotics within 3 months before sampling and ileal disease or resection. Bacterial composition of the microbiota in term of main phylogenetic groups and bacterial species, was performed using quantitative real-time polymerase chain reaction. In dry stools, after proteic extraction, hBD1 and HD5 were measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Using Pearson test, correlation between the bacterial composition of the microbiota and intraluminal rate of human defensins has been investigated.

Results: Dysbiosis has been observed in IBD characterized by a low counts of Firmicutes (Clostridium leptum p < 0.0001, Clostridium coccoides p < 0.0001 groups) and Faecalibacterium prausnitzii p = 0.0006 at the species level. Enterobacteria group (p = 0.0003) and Escherichia coli (p = 0.0002) were more abundant in patients with an active IBD. In parallel, hBD1 was decreased in faecal samples of IBD patients (168.2±158.7 ng/g feces) compared to healthy subjects (296.8±180.9 ng/g feces, p = 0.005). It was the same for HD5 (16.8±15.3 ng/g feces in IBD vs 66.2±35.8 ng/g feces in healthy subjects, p < 0.0001). We observed that hBD1 expression was positively correlated to F. prausnitzii counts and negatively correlated to the Bifidobacteria counts. HD5 expression was positively correlated to F. prausnitzii and C. leptum counts and negatively correlated to E. coli, Enterobacteria and C. coccoïdes counts.

Conclusion: Our results confirmed a dysbiosis in IBD centered by low counts in Firmicutes and especially F. prausnitzii. This dysbiosis was associated with an intraluminal decrease of hBD1 and HD5 rates in colonic IBD. Correlations between some bacterial groups and the drop of hBD1 and HD5 suggest a direct or indirect regulation of intraluminal AMP by intestinal bacteria or its metabolites. IBD dysbiosis could therefore play a role in a chronic intestinal inflammation disturbing AMP secretion.