Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial

Abstract

BackgroundFecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI).AimsTo compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema.MethodsIn a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100–200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied.ResultsAdverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema.ConclusionsThe route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product.Trial registrationClinicalTrials.gov NCT02449174

An oral FMT capsule as efficient as an enema for microbiota reconstruction following disruption by antibiotics, as assessed in an in vitro human gut model.

“…To date, few studies in humans have already compared the e ciency of oral capsules (frozen or lyophilized) for rCDI treatment to more traditional FMT routes such as colonoscopy or enema. In line with our results, available data indicates that oral capsules are as effective as traditional modes of administration, especially to restore bacterial diversity [18,43]. Lastly, Allegretti and colleagues (2019) [41] have shown in humans that the lower dose treatment with colonic release capsules (10 capsules in a single administration) was equally effective to cure rCDI as the higher treatment-dose (30 capsules).…”

“…The oral capsule proved almost as e cient as enema forms (− 3.8 dysbiotic days), even if the amount of administered bacteria was 100 times lower and required a longer administration period (1 week compared to two days). In previous studies, two approaches were mainly developed for FMT oral capsules, rst freezing at -80 °C with glycerol, then more recently freeze-drying with various cryoprotectants, as performed in the present study [41][42][43]. Interestingly, Jiang and colleagues (2017) [42] showed in mice that there was no difference in e ciency of frozen and lyophilized capsules in rCDI treatment, and that products can be stored up to 7 months without losing microbiota composition and therapeutic e cacy.…”

The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis

“…A burgeoning literature has emerged on fecal microbiota transplant (FMT), the transfer of minimally processed stool from a donor to a recipient. Clinical resolution is associated with increased microbial diversity and secondary bile acids, providing proof of concept of the critical role of microbiome restoration [11][12][13].…”

Insights into the role of intestinal microbiota in hematopoietic stem-cell transplantation

“…99 The choice must be based on the balance of risk and benefits for each method, considering the clinical setting in which FMT is performed. It is worth mentioning that an oral capsule seems to maintain the efficacy and safety of other routes, and is less invasive for the patient, 100 even if a substantial number of capsules is required to achieve the necessary microbial load. 101 Optimization of all these practical aspects still needs to be addressed in the future.…”