The Effect of Therapeutic Fecal Transplant on the Gut Microbiome in Children With Ulcerative Colitis

The enteric microbiota is now accepted as an important etiologic factor in the pathogenesis
of human Inflammatory Bowel Disease (IBD) and immune-mediated chronic experimental intestinal
inflammation, with ample data to implicate the microbiome as a main factor in the occurrence
of IBD. This can be inferred from animals in germ-free environment which can protect from
experimental colitis. In addition, increased gut permeability due to dysbiosis, is frequently
seen in patients with IBD even in remission and, similarly, first degree relatives of IBD.
Therefore, it is not surprising that therapeutic interventions aiming at modifying the gut
microbiome would be of therapeutic benefit. Ulcerative colitis is a condition that is
characterized by chronic inflammation of the colon. It is an important pediatric disease as
25% of all cases begin in childhood and its incidence is continuously on the rise. It is
believed to be related to a genetically and environmentally-generated altered immune response
to the enteric microbiome. Previous work in the PI's laboratory suggests that children harbor
a unique gut microbial profile, which can predict therapeutic response. Therefore, modifying
the gut microbiome may result in therapeutic benefit. However, attempts to modify the gut
microbiome were largely unsuccessful until the advent of fecal transplant, which is a new
approach in treating colitis. Fecal microbiota transplant (FMT) has been introduced several
decades ago in an attempt to restore the gut microbial balance and it appears to be a more
efficient method to effectively change and sustain the gut microbial composition. To date
there have been a number of successful reports to suggest control of disease activity and in
some cases cure of the disease. This study aims to further determine the safety and efficacy
of FMT in treating children with ulcerative colitis

Inclusion Criteria

1. Age: 7-21 who have been diagnosed with ulcerative colitis

2. Mild to moderate disease based on PUCAI with a score of 10-64

3. Need for colonoscopy

Exclusion Criteria

1. Children who are known to be resistant to steroid therapy, immunomodulators and
biologics, or on a steroid dose greater than 0.5 mg/kg/day (maximum 20 mg)

2. Children with recent dose change of biologics (within 4 weeks), 5-ASA, steroids or
immunomodulators (within 4 weeks)

3. Allergy to or intolerance of mesalamine or 5-ASA products

4. Any evidence of infectious colitis

5. Concurrent infections that require anti-microbial therapy (such as abdominal abscess,
pneumonia, etc…)

6. Unable to give informed consent/assent

7. Have received probiotic preparations ≤ 4 weeks prior to randomization

8. Pregnancy and breast feeding in patient subjects of childbearing potential

9. Subjects with significant renal and liver dysfunction (creatinine > 2 mg/dl and direct
bilirubin > 2 mg/dl), Subjects with congenital or acquired immunodeficiency, or who
are immunosuppressed due to conditions other than ulcerative colitis (such as
neoplastic disease or organ transplantation), have received or are receiving
chemotherapy, or have been diagnosed with HIV.