To compare the safety and efficacy of concomitant LFMT versus placebo in UC patients who are starting vedolizumab or ustekinumab.

This is dual-center, randomized, double-blind, placebo-controlled pilot trial for UC patients with active disease who are being initiated on treatment with vedolizumab or ustekinumab.

The study will recruit 40 outpatients at 2 Canadian healthcare centres at the University of Alberta Hospital (University of Alberta), and the University of Manitoba.

Inclusion Criteria:

1. 18 years of age or older but less than 75 years of age

2. Able to provide informed consent

3. Established ulcerative colitis diagnosis determined by a physician through standard endoscopic and histologic criteria

4. Active UC defined as total Mayo score between 6-12 AND Mayo endoscopic sub-score >1 with disease that extends 15 cm or more from the anal verge

5. Selected by treating physician for initiation of biologic treatment with either vedolizumab or ustekinumab. Patients must be:

   • Biologic naive; OR
   • Have failed anti-TNF, anti-integrin, anti IL12/23 or oral small molecules

6. Use of effective contraception method for women of childbearing potential for at least 4 weeks prior to receiving study treatment and for the duration of the trial

7. Willing and able to comply with all required study procedures

Exclusion Criteria:

1. Severe UC requiring hospitalization

2. Indeterminate colitis

3. Evidence of or treatment for C difficile infection or other intestinal pathogen, including CMV, within 4 weeks prior to enrollment

4. Evidence of toxic megacolon or gastrointestinal perforation on imaging

5. Abdominal surgery within the past 60 days

   • Neutropenia with absolute neutrophil count <0.5 x 109/L
   • Peripheral white blood cell count > 35.0 x 109/L and fever (>38 degrees Celsius)
   • Planned or actively taking another investigational product
   • Uncontrolled medical conditions such as psychiatric disorders or substance abuse
   • Severe underlying disease such that the patient is not expected to survive for at least 30 days

6. Pregnant or lactating

7. Unwilling to discontinue non-dietary probiotic

8. Antibiotic use in the past 30 days or anticipated need for systemic antibiotic use during study

9. FMT within 3 months prior to enrollment

10. Use of the following medications:

    1. rectal/topical therapy within 2 weeks of screening
    2. cyclosporine, tacrolimus or thalidomide within 4 weeks of screening
    3. tofacitinib within 4 weeks of screening
    4. adalimumab or infliximab within 8 weeks of screening
    5. vedolizumab within 8 weeks of screening
    6. ustekinumab within 12 weeks of screening
    7. prednisone > 30 mg/d

11. Investigator deems enrolment in the study is not in the best interest of the patient

To maintain blinding, LFMT and placebo capsules will appear identical.