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P692. Quorum sensing driven by N-acyl-homoserine lactone in inflammatory bowel diseases associated dysbiosis

C. Landman1, A. Besse1, M.-A. Maubert1, L. Brot1, L. Humbert1, J. Cosnes2, L. Beaugerie2, G. Trugnan1, H. Sokol1, D. Rainteau1, Q. Elodie1, P. Seksik1, 1St Antoine Hospital, Inserm Erl U 1057, UMR 7203, Paris, France, 2St Antoine Hospital, Gastroenterology, Paris, France

Background

Dysbiosis is a key factor in inflammatory bowel diseases (IBD) physiopathology. Quorum sensing (QS) driven by N-acyl-homoserine lactone (acyl-HSL), a bacterial communication network, has not been studied in the human gut microbiota yet and could be involved in dysbiosis.

The aims of this study were to look for acyl-HSLs in human gut microbiota and to investigate their features in IBD associated dysbiosis.

Methods

Fecal samples from 19 IBD patients in remission (n = 10) and during flare (n = 9) and from 11 healthy subjects (HS) were analyzed.

After extraction, an acyl-HSL profile was determined for each sample using HPLC coupled with tandem mass spectrometry. Concentrations were estimated by AUC of each peak (arbitrary units ±SEM). Acyl-HSL biologic activity was validated on a bacterial biosensor (Agrobacterium tumefasciens NTL4).

In parallel, fecal microbiota composition was assessed by real-time quantitative PCR.

For statistical analysis, a non parametric test was used.

Results

Nine acyl-HSLs were identified in fecal samples while 2 were prominent: acyl-HSL at m/z 216.1 (3-OH-C6-HSL) and acyl-HSL at m/z 294.2 (3-oxo-C12:2-HSL or C13:2-HSL) recognized by NTL4 biosensor.

Their concentrations differed between IBD patients and HS: acyl-HSL at m/z 216.1 was significantly increased in inactive IBD compared to HS (AUC = 2897±572 vs 1242±353, P = 0.04) and acyl-HSL at m/z 294.2 was significantly decreased in active IBD (AUC = 2726±2726) compared to HS (AUC = 30532±12230, P = 0.007) and to inactive IBD (AUC = 26409±12291, P = 0.02).

In parallel, dysbiosis was observed in active IBD: low counts in Firmicutes (C. coccoides P = 0.01 and C. leptum P = 0.003 including F. prausnitzii P = 0.04), significant increase in lactobacilli (P = 0.002) and non significant increase in E. coli (P = 0.6).

In samples with high acyl-HSL at m/z 294.2 (concentration above median), C. leptum was significantly more represented (10.22±0.07 vs 9.72±0.19 log/g of feces, P = 0.046). In these samples, there was also a trend towards higher counts in C. coccoides (P = 0.06) and lower counts in E. coli (P = 0.09).

Conclusion

Our study showed for the first time that QS driven by acyl-HSLs occurs in human gut microbiota.

Moreover, in IBD, acyl-HSLs profile characterized by prominent acyl-HSL at m/z 216.1 and a decrease in acyl-HSL at m/z 294.2 during flare differs from HS. The lack of this acyl-HSL was associated with low counts in Firmicutes.

These results invite us to investigate acyl-HSL functional role in dysbiosis onset and in host physiology.