BACKGROUND AND RATIONALE Fecal microbiota transplant (FMT) is an established treatment for
the management of recurrent Clostridioides difficile (CDI) infection in children and adults,
including children with underlying immunodeficiency syndromes and extensive surgical
resection. While CDI is the most common indication for FMT, this intervention has also been
studied for Crohn's disease, ulcerative colitis, autism, and small intestinal bacterial
overgrowth (SIBO). SIBO is a disorder in which the small bowel is colonized by excessive
aerobic and anaerobic microbes normally present in the colon. This condition may cause
malabsorption, bloating, bloodstream infections (BSI), and D-lactic acidosis (DLA). Treatment
traditionally involves broad-spectrum antibiotic use yet this approach may promote persistent
dysbiosis, multidrug resistant organisms (MDROs), and often lacks clinical efficacy. Patients
with short bowel syndrome (SBS), which involves intestinal resection, dysmotility, and
altered enteral feeding are at highest risk for SIBO. Pediatric SBS SIBO patients face
significant impacts on quality of life, and higher rates of bacteremia and liver disease.
Specific Aims i. To determine the feasibility, and safety of administering an FMT based
treatment to pediatric SBS patients with SIBO. This aim will include measures of adverse
events, acceptability to children and parents, ease of administration and sample collection.
ii. To determine short-term clinical efficacy of FMT for the treatment of SIBO. This aim will
include measures of time to symptom resolution, completeness of symptom resolution, change in
enteral feeding tolerance, and development of any new clinical gastrointestinal symptoms
after FMT. Weeks 1-4 after FMT.
iii. To determine long-term clinical efficacy of FMT for the treatment of SIBO. This aim will
include measures of durability of remission, including time to recurrence of symptom
resolution, severity of clinical symptoms if recurrence, sustained changes in feeding
tolerance, and efficacy of repeat FMT administration (second treatment). Week 8 after FMT.
iv. To assess changes in intestinal microbial composition and function before and after FMT.
This aim will attempt to identify functional changes in the intestinal microbiome that
correlate with symptom resolution. These data will support future translational and clinical
studies with our collaborators and support the development of new therapeutic innovations.
D. TRIAL OBJECTIVES Our objectives are to assess feasibility, and clinical efficacy of this
intervention in children (Table 2).
Feasibility Objectives:
Acceptability of this intervention for patients and families, ability of patients and
families to conduct the required screening to monitor efficacy and recruitment rate of
patients to the study.
Clinical Objectives:
Clinical efficacy of treating SIBO in our patient population using FMT. These outcomes will
be collected at the following timepoints: baseline (pre-FMT), one-, four-, and eight-weeks
post-FMT administration
E. STUDY DESIGN AND DURATION We will recruit 5-17-year-old patients with intestinal resection
(any length), experiencing an active episode of SIBO (diagnosed through lactose breath
testing and gastrointestinal symptom scores). Patients will discontinue antibiotics for >1
week prior to FMT. FMT infusions will be administered through patients' enteral tubes
(nasogastric, gastrostomy, jejunostomy), or via endoscopy (duodenal infusion).
Patients will receive a single FMT (Week 0). They will then have outcomes (including a
combination of clinical symptom scores, blood, stool and urine testing) measured one week
after FMT, four weeks after FMT, and eight weeks after FMT.
As this is an open-label trial, there will be no randomization or blinding required. A
placebo / comparative treatment will not be assessed.
All FMT treatments will be conducted at MCH, using local pediatric stool bank materials.
Patients will have follow-up monitoring, per protocol through their local institution
(MCH/HSC). Serial measurements of biological, clinical and microbial outcomes will occur, per
protocol.