microorganisms as triggers in acute severe ulcerative colitis and their influence on medical therapy efficacy: a multi-omics pilot approach.

Conditions: Inflammatory Bowel Diseases; Colitis; Ulcerative

Summary: this pilot prospective study will investigate the role of microbiota and known enteropathogens in acute severe ulcerative colitis (asuc). investigators will compare a group of patients hospitalized for an asuc with patients experiencing a non-severe ulcerative colitis (nsuc) flare by investigating microbiome, metabolome and transcriptome and integrating this data through a multi-omic framework. this systems biology approach aims at enhance our understanding of this severe event, define diagnosis and prognosis biomarkers to improve medical therapy and avoid colectomy and/or death.

ulcerative colitis (uc) is one of the two entities of inflammatory bowel disease (ibd), along with crohn's disease. one in 4 patients experiences an acute severe ulcerative colitis (asuc) during the disease course, defined as a severe flare with systemic inflammation. asuc is a medical and surgical emergency as complications and death may occur when patients do not respond to medical therapy and require salvage colectomy. little is known about the pathophysiology and specifically the triggers of asuc. at baseline, investigators will investigate the presence of a microbiome signature in patients with an asuc compared with patients with a non-severe uc flare (nsuc). to identify the role of microorganisms, investigators will look specifically for known enteropathogens, i.e. clostridium difficile and cytomegalovirus. investigators will investigate the impact of microbiota disruptors, such as antibiotics, nsaids and diet on microbiota and patients' outcomes. to evaluate the role of the host inflammatory pathways, investigators will study the colonic mucosa transcriptome and the host metabolome, focusing on anti-microbial defence pathways, regarding the suggested role of defective immune defence pathways in ibd pathogenesis. investigators will focus on the il23 and jak pathways, since new drugs targeting these molecules are now available for ibd patients but still not recommended in the asuc setting. our last approach will be to evaluate the predictability of the response to therapy according to baseline and early changes of stool microbiome and host metabolome.

Eligibility criteria:
inclusion criteria: all patients: * adult patients diagnosed with ulcerative colitis according to usual criteria. * free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research). asuc group: adult patients hospitalized an asuc defined according to truelove criteria, i.e. ≥6 bloody daily stools with one or more of the following criteria: temperature \>37.8°c, pulse \>90 beats/min, haemoglobin \ 45mg/l. non severe acute uc patients (nsuc) group: adult patients with disease activity symptoms, corresponding to a partial mayo score of 4 or more with a rectal bleeding subscore of at least 1, without truelove severity criteria. exclusion criteria: * patients with perianal lesions, ileal lesions or endoscopic aspect of the colonic lesions related to a crohn's disease acute severe colitis. * patients under 18 years old. * patients under legal protection or unable to express their consent. * patients not affiliated to a health insurance system. * patients deprived of liberty by judiciary or administrative decision or hospitalized without consent or admitted in a sanitary or social institution for another reason than research

Keywords: inflammatory bowel disease acute severe ulcerative colitis microbiome prognostic factors