P836 Biomarkers response to anti-TNF treatment in Crohn’s disease through the intestinal microbiota

Abstract

Abstract Background The alteration of the intestinal microbiota is a necessary requirement for the development of Crohn’s disease (CD). The anti-TNF alfa (TNF) treatment has radically changed the prognosis of the disease, modifying the therapeutic objective which is the induction and subsequent maintenance of mucosal healing. It is unknown, if this cure/improvement correlates with changes in the microbiota. The objectives of the study were: evaluate the changes in the microbiota in CD pre and after six months with TNF, determine the changes in the microbiota based on the clinical-biological response to TNF and calculate the F. prausnitzii/E. coli (F/E) ratio as an indicator of therapeutic response. Methods This was a prospective observational multicentre study that included 27 patients with CD who started treatment with TNF. 16 healthy individuals were included to establish the local healthy microbiota. The existence of disease activity was determined using the Harvey-Bradshaw index (HBI), analytical parameters such as C-reactive protein and faecal calprotectin measured at the beginning of the study, 3 and 6 months; classifying patients as responders (R) and non-responders (NR). The composition of the microbiota (the alpha and beta diversity), as well as the F/E ratio as indicators of dysbiosis, were evaluated by massive genomic sequencing, at the date of inclusion and 6 months after starting TNF through faecal samples. Results Prior to TNF, the loss of Clostridia class genera, producers of short chain fatty acids, as well as the significant increase (p <0.01) of Proteobacteria, highlighting the Escherichia/Shigella genus with respect to healthy controls. The microbiota varied according to response to the TNF: the Proteobacteria phylum affected in NR with respect to healthy and R group (p <0.005). Although, R group (13/27) significantly increase Clostridia class bacteria (such as Faecalibacterium) as well as alpha diversity with respect to NR group (p <0.01), with a tendency towards a microbiota similar to controls. There is a significant association (p <0.001) in the F/E relationship between the R group and NR group The F/E ratio was the most accurate (area under a curve of 0.87), when, we compare this value with HBI and CF as biomarkers of response to TNF. Conclusion The anti-TNF treatment allows partial restoration of the intestinal microbiota in responders with a tendency towards eubiosis, with respect to non-responders. The determination of F. prausnitzii/E. coli ratio can provide a reliable indicator of response to anti-TNF treatment in Crohn’s disease.