San Diego, CA, May 22, 2016—In several measures of microbial engraftment, encapsulated fecal microbiota transplantation (FMT) may be equivalent to traditional delivery modalities—including colonoscopy and nasogastric tube (NGT)—in patients with recurrent Clostridium difficile
infection, with an initial course of low-dose capsules being the best approach to reduce any procedure-related risks, according to researchers here at Digestive Disease Week 2016.
“C. difficile is a major public health concern, and 20% to 30% of patients will experience recurrent disease. We now know that FMT is an effective therapy for the treatment of recurrent C. difficile. However, the standard modality of delivery right now in the US is via colonoscopy,” explained Jessica R. Allegretti, MD, MPH, of Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA. “We aimed to look at not only the clinical effectiveness of oral encapsulation of FMT, but also at how well those capsules engrafted, compared to standard modalities,” she added.
Dr. Allegretti and colleagues conducted this open-label, cluster, dose-finding study at two academic centers in 19 patients to assess the rates of microbial engraftment with FMT capsules, studying the microbiome profile of patients treated with FMT capsules compared with those who had FMT delivered by colonoscopy and nasogastric tube.
At one site, patients with recurrent C. difficile infection were randomized to low-dose FMT capsules, taking 30 pills at once. At the other site, patients were treated with high-dose FMT capsules, taking 30 pills daily for 2 consecutive days. These capsules were produced from healthy, rigorously screened unrelated donors from a universal public stool bank (mean age: 26 years; mean BMI: 22.2 kg/m2; mean waist circumference: 32.5 inches) using a scalable, physically stable (greater than 30 days at 25° C) emulsion-based production protocol. In both arms, patients who were non-responders were treated with a high dose capsule.
In a subgroup of six high-dose patients, 16S rRNA sequencing was done on donors and patients before and 8 weeks after FMT dosing, and researchers compared these with previously published data from FMT by colonoscopy and NGT (Youngster et al. CID. 2014).
At the 8-week follow-up, Dr. Allegretti and colleagues found no adverse events with either dose.
“[There were] no adverse events. Patients tolerated the capsules very well. Maybe some mild nausea or abdominal pain on the day of administration, but that was minimal. No vomiting, no fevers, nothing like that,” noted Dr. Allegretti.
In the high-dose group, 77% achieved diarrhea resolution, compared with 70% of patients in the low-dose group (P=0.15). Five patients were non-responders, and all were treated with high-dose FMT capsules. A full 80% achieved clinical cure, resulting in a 94% aggregate cure rate.
Figure 1. Gut microbiota diversity as measured by the Shannon Diversity Index in pre-FMT samples (orange) and post-FMT sample (blue), compared to donors (green) across the three FMT delivery modalities. FMT by either capsules, colonoscopy and NGT is able to recover the diversity found in the donor community.
Using the 16S data, researchers observed an increase in diversity after FMT via capsule (1.96) similar to historical data from FMT via colonoscopy (1.07) and NGT (1.45). After FMT, recipient microbiomes were more similar to donors than pre-FMT (see Figure 2). After FMT, median Jensen-Shannon Divergence between donors and recipients was 0.51, and was similar to that achieved after FMT by NGT (0.38) or colonoscopy (0.42).
Figure 2 – Gut microbiota community divergence. The Jensen-Shannon Index measures the distance of a given fecal microbial community from the community found in healthy donors. The lower the divergence, the closer the community is to the healthy donor. All three FMT delivery modalities (capsule, colonoscopy or NGT) restore gut microbial structure and bring it closer to the gut microbiome of a healthy donor.
“FMT is an effective therapy for recurrent C. difficile, and capsule formulation seems to work very well. Colonoscopy still seems to be slightly more effective than capsules, but the benefit of capsules are that you reduce procedural-related risks with the colonoscopy. Additionally, we now know that engraftment seems to be equally as good with capsules compared to traditional methods,” concluded Dr. Allegretti.