Fresh Versus Frozen Versus Lyophilized Fecal Microbiota Transplant for Recurrent Clostridium Difficile Infection

Abstract

Introduction: Clostridium difficile Infection is a significant source of morbidity and mortality, which is on the rise. Fecal Microbiota Transplantation (FMT) is an alternative therapy to antibiotics with a high success rate and low relapse rate. Current data regarding the efficacy of the types of FMT used, namely fresh, frozen, and lyophilized is conflicting. Our review attempts to consolidate this data and highlight the most efficacious treatment currently available.Methodology: MEDLINE, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, SciELO, the Korean Citation Index, and Global Index Medicus were systematically searched from inception through May 3, 2022. Studies in which patients are undergoing any form of FMT who had failed antibiotic treatment previously were included. Both pairwise (direct) and network (direct + indirect) meta-analysis were performed using a random effects model and DerSimonian-Laird approach. A frequentist approach was used for network meta-analysis. Risk differences with (RD) with 95% confidence interval (CI) were calculated.Results: A total of 8 studies, including 4 RCTs and 4 cohort studies, were included with a total of 616 patients. Fresh FMT was determined to be most successful with 93% efficacy 95% CI (0.913 to 0.999) followed by frozen with 88% efficacy 95% CI (0.857 to 0.947) and lyophilized with 83% efficacy 95% CI (0.745 to 0.910). The direct meta-analysis showed no statistically significant difference between fresh and frozen group. (RD −0.051 95% CI −0.116 to 0.014 P = 0.178). No significant differences were noted in frozen versus lyophilized groups with an overall trend towards Fresh FM (RD −0.061 95% CI −0.038 to 0.160 P = 0.617). On network metaanalysis, when compared with fresh group, a lower recovery rate was noted with both frozen group (RD −0.06 95% CI −0.11 to 0.00 P = 0.05) and lyophilized group (RD −0.16 95% CI −0.27 to −0.05 P = 0.01). Conclusion:We conclude the efficacy of Frozen and Lyophilized preparations is high with no difference in direct comparison, and the relative efficacy reduction based on network analysis is outweighed by the safety, accessibility, and practicality of Frozen or Lyophilized preparations.

Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent <i>Clostridioides difficile</i> Infection

“…Another recent network meta-analysis further supports the use of frozen or lyophilized stool for FMT. While there appears to be a marginal decrease in relative efficacy (fresh FMT: 93% efficacy [95% CI: 0.913 to 0.999]; frozen FMT: 88% efficacy [95% CI: 0.857 to 0.947]; lyophilized FMT: 83% efficacy [95% CI: 0.745 to 0.910]), this slight reduction seems to be outweighed by the accessibility and practicality of frozen or lyophilized preparations [32].…”

The practice of fecal microbiota transplantation in inflammatory bowel disease

“…Prolonged frozen storage leads to an increase in Firmicutes to Bacteroidetes ratio, as some Gram-negative species are depleted during storage and some hypothesize that trials in which frozen FMT was found to be effective also depend on this phenomena of selective depletion of administered Bacteroidetes . A network metaanalysis of 8 studies in patients with recurrent C. difficile infection (CDI) found similar efficacy in fresh versus frozen FMT (93% vs. 88%, P = 0.18) and concluded that the trend towards improved efficacy with fresh FMT was offset by safety, accessibility, and practicality of frozen FMT [ 54 ]. Similar findings have been observed in UC from meta-analyses of 22 studies where the efficacy of fresh (34.4%) versus frozen (46.8%) was similar [ 55 ].…”

Past, present, and future of microbiome-based therapies

“…Meta-analyses have shown that, among these, colonoscopy is the most effective mode of delivery, with no significant differences compared to oral administration (> 80% overall) [132,137,138] . Importantly, the upper delivery method has shown additional advantages in treating immune-related disease, likely due to immune regulation in the small intestine [127,139] .…”

“…Because the microbiome plays a key role in modulating the immune system, FMT treatment is being tested in an array of immune-related diseases, ranging from acute graft-versus-host disease (GVHD) to Type I diabetes or Multiple sclerosis, with variable but again promising results, especially in the treatment of GVHD [14,139] . Increasing data demonstrate that the ability of the gut microbiome to metabolize xenobiotic compounds and to regulate immune responses has profound consequences for anticancer therapies [15,31,53] .…”

“…Because FMT requires administration by medical staff, and the effectivity using enemas has been variable, public organizations and biotech companies are developing non-invasive, safe, and efficacious alternatives [ Figure 3 ]. The use of oral capsules containing donor-derived lyophilized fecal material has proven to be almost as efficient as traditional FMT [ 140 ] . Moreover, to make more sanitary products and decrease the possibility of transferring undesired pathogens or toxic metabolites, companies are creating purified whole microbial ecosystem products.…”