The primary goal of the study is to develop an early (within 4 weeks) combined microbiota/metabolic signature predicting clinical response upon anti-inflammatory treatment in UC patients.

The investigators perform a longitudinal prospective multi-center study for ulcerative colitis (UC) patients with a flare at/and after the time of starting a new treatment and healthy household controls. They will perform intense longitudinal bio-sampling and deep clinical characterization.

With this information the aim is to develop a predictive signature regarding the success of a new ly started anti-inflammatory therapy after an UC flare.

Inclusion criteria ulcerative colitis:

1. Signed informed consent
2. Age 18-80 years
3. General ability to understand and follow study procedures, fluency in German, French, or English
4. Diagnosis of ulcerative colitis since ≥3 months
5. Confirmed flare of ulcerative colitis with partial SCCAI score ≥5 points and at least one biomarker supporting intestinal inflammation
6. Planned start with ozanimod, steroids (prednisone ≥20mg/d or equivalent), or a biological (vedolizumab, infliximab, adalimumab, golimumab, ustekinumab)

Exclusion criteria ulcerative colitis

1. Confirmed cytomegalovirus (CMV) reactivation within the previous 2 weeks (tested as part of standard medical practice at the discretion of the responsible physician)
2. C. difficile related diarrhea, or other confirmed infectious diarrhea in the last 4 weeks (tested as part of standard medical practice at the discretion of the responsible physician)
3. Diagnosis of Crohn's disease
4. Current pouch or ileostomy/ colostomy
5. Severe medical, surgical, or psychiatric comorbidities interfering with study procedures

Inclusion criteria controls

1. Signed informed consent

2. Age 18-80 years

3. General ability to understand and follow study procedures, fluency in German, French, or English

4. No current or past diagnosis of inflammatory bowel disease (IBD)

5. No current medical complaints typic for IBD e.g.

   • Diarrhea, severe constipation, abdominal pain, blood in stool, weight loss
   • Slight symptoms (without impact onto daily activities) are permitted

6. No other current relevant gastrointestinal disease or condition plausibly interfering with microbiota assessment according to the discretion of the study physician

Exclusion criteria controls

1. Confirmed cytomegalovirus (CMV) reactivation within the previous 2 weeks
2. C. difficile related diarrhea, or other confirmed infectious diarrhea in the last 4 weeks
3. Diagnosis of Crohn's disease, ulcerative colitis
4. Current pouch or ileostomy/ colostomy
5. Severe medical, surgical, or psychiatric comorbidities interfering with study procedures

Patients/ participants fulfilling inclusion criteria to one of the following groups will be included:

1. Patients with a flare of ulcerative colitis who meet the inclusion criteria (see above). Inclusion of 120 patients is planned.
2. Healthy controls. For each patient, a healthy control individual who shares the same living conditions (e.g., spouse or roommate) is attempted. Enrolment of controls will not be enforced but enrolment of ≥100 controls for 120 patients is expected.

Analytic code for generation of the predictive signature will be made available to other researchers

With publication of results

Acess to analytic code will be detailed in the final publication