Impact of Fecal Biotherapy (FBT) on Microbial Diversity in Patients With Moderate to Severe Inflammatory Bowel Disease
| Status: | Completed |
|---|---|
| Conditions: | Irritable Bowel Syndrome (IBS), Gastrointestinal, Crohns Disease |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/4/2017 |
| Start Date: | May 2013 |
| End Date: | November 2016 |
The human immune system is usually tolerant of the millions of beneficial commensal bacteria
(the microbiome), which colonize the healthy intestinal tract. In contrast, patients with
Inflammatory Bowel Disease (IBD) may play host to an imbalanced mix of such intestinal
bacteria, which initiates abnormal immune responses in susceptible individuals. The
resulting inflammation that occurs in the gastrointestinal tract damages the intestinal
lining, leading to symptoms (such as intractable diarrhea, pain or weight loss), heightened
cancer risk, other serious complications with substantial morbidity and even death. Current
therapies for IBD focus on suppressing the excessive immune response to these bacteria, but
have major side effects and do not address any role of the microbiome in disease
development.
The investigators hypothesize that there is heightened intraluminal generation of
pro-inflammatory factors by luminal "pathogenic" bacteria, such as extracellular nucleotides
and purinergic derivatives, which trigger host immune cells. This results in loss of
suppressive T regulatory cells with unrestrained immune cell deviation to pathogenic T
helper cells that cause inflammatory responses. The investigators' proposal is that
correcting the disease-provoking microbiome would beneficially improve gut microbial
diversity, alter immune responses elicited in patients by such microbial products of
pathogenic bacteria, and ultimately limit and suppress disease activity.
To test the hypothesis, the investigators propose to enroll patients with active Crohn's
Disease, and introduce the microbiome of healthy and unrelated individuals to patient's
intestinal tract, via fecal biotherapy (FBT) with all applicable safety measures. The
investigators propose to comprehensively test the effects of FBT on the host microbiome,
determine microbial production of inflammatory nucleotides and derivatives, which the
investigators suggest might impact the host immune response and disease activity in patients
with IBD.
(the microbiome), which colonize the healthy intestinal tract. In contrast, patients with
Inflammatory Bowel Disease (IBD) may play host to an imbalanced mix of such intestinal
bacteria, which initiates abnormal immune responses in susceptible individuals. The
resulting inflammation that occurs in the gastrointestinal tract damages the intestinal
lining, leading to symptoms (such as intractable diarrhea, pain or weight loss), heightened
cancer risk, other serious complications with substantial morbidity and even death. Current
therapies for IBD focus on suppressing the excessive immune response to these bacteria, but
have major side effects and do not address any role of the microbiome in disease
development.
The investigators hypothesize that there is heightened intraluminal generation of
pro-inflammatory factors by luminal "pathogenic" bacteria, such as extracellular nucleotides
and purinergic derivatives, which trigger host immune cells. This results in loss of
suppressive T regulatory cells with unrestrained immune cell deviation to pathogenic T
helper cells that cause inflammatory responses. The investigators' proposal is that
correcting the disease-provoking microbiome would beneficially improve gut microbial
diversity, alter immune responses elicited in patients by such microbial products of
pathogenic bacteria, and ultimately limit and suppress disease activity.
To test the hypothesis, the investigators propose to enroll patients with active Crohn's
Disease, and introduce the microbiome of healthy and unrelated individuals to patient's
intestinal tract, via fecal biotherapy (FBT) with all applicable safety measures. The
investigators propose to comprehensively test the effects of FBT on the host microbiome,
determine microbial production of inflammatory nucleotides and derivatives, which the
investigators suggest might impact the host immune response and disease activity in patients
with IBD.
Inclusion Criteria (Patients):
- CD confirmed by biopsy for > 3 months duration
- Active disease (Harvey-Bradshaw Index > 5
- Failed standard therapy with; stable doses of 5-ASA >2 weeks; thiopurines >3 months;
or is steroid dependent at a dose <20mg/d; (inability to taper off steroid for longer
than 1 week)
- Stable medication regimen for >2 weeks.
- Age > 18 years old
Exclusion Criteria (Patients):
- Diagnosis of indeterminate colitis, or proctitis alone
- Severe or fulminate colitis
- Women who are pregnant or nursing
- Patients who are unable to give informed consent
- Patients who are unable or unwilling to undergo colonoscopy with moderate sedation
(>ASA class II)
- Patients who have previously undergone FMT
- Patients who have a confirmed malignancy or cancer
- Patients who are immunocompromised
- Treatment within last 12 weeks with cyclosporine, tacrolimus, infliximab, adalimumab,
certolizumab, natalizumab, thalidomide
- Antibiotic use within 2-months of start date
- Participation in a clinical trial in the preceding 30 days or simultaneously during
this trial
- Probiotic use within 30 days of start date
- Rectal therapy within 14 days of start date
- Decompensated cirrhosis
- Congenital or acquired immunodeficiencies
- Other comorbidities including:
- Diabetes mellitus, cancer, systemic lupus, must be able to tolerate conscious
sedation with colonoscopy
- Chronic kidney disease as defined by a GFR <60mL/min/1.73m2 44
- History of rheumatic heart disease, endocarditis, or valvular disease due to risk of
bacteremia from colonoscopy
- Steroid dose >20mg/day
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