Faecal microbiota transplantation (FMT) is the standard-of-care for recurrent or refractory Clostridioides difficile infection (CDI) 1. Numerous variables impact the effectiveness of FMT, including donor, recipient, processing and administration factors. With the expanding use of FMT, it is important to determine the optimal treatment regimen to improve outcomes for patients with CDI and beyond. Paaske et al. carried out an eloquent multi-centre quality-improvement process, aimed at increasing CDI cure rates for patients undergoing FMT 2. They implemented a number of interventions to enhance the effectiveness of FMT, showing that dose and donor matter. In this real-world study, eight-week cure rates of CDI-associated diarrhoea (CDAD) were increased across seven centres from 50% (95% confidence interval CI 45%–56%) to 59% (55%–63%), after the exclusion of three low-performing donors. Two donors had previous cure rates of less than 35%, and the third was observed to have a sudden decrease in effectiveness. Whilst the concept of an FMT super-donor has gained traction in inflammatory bowel disease, its relevance in CDI remains unclear, owing to consistently high cure rates 3. The current data highlight the need for improved FMT regimens, with real-world efficacy lower than that reported in clinical trials 2, 4. However, donor factors are not clearly elucidated in this study; rather donor performance is measured on prior outcomes. Donor factors previously associated with reduced efficacy include antibiotics within 3–12 months of donation, and donations with a Bristol Stool Form Scale of ≤ 3 5. Donor sex, BMI, smoking status, H. pylori status, birth-mode and donation-weight have not been found to influence the effectiveness of FMT in CDI. Selection of a super-donor has been trialled in one small pilot study in CDI, in which a single donor was selected from nine healthy candidates based on balanced Bacteroidetes/Firmicutes ratio, high stool butyrate concentration, and high alpha-diversity and phylogenetic-diversity 6. CDI cure at week 10 was achieved in 10/10 patients with recurrent CDI, demonstrating that donor selection is feasible and may offer increased efficacy. Paaske et al. further increased their CDAD cure rates from 59% (55%–63%) to 72% (65%–77%) by implementing an optimised dosing regimen of two-dose capsule FMT 2. Repeated FMT has been shown to increase clinical effect at week eight compared to single-dose FMT (91% vs. 84%), although it remains unclear which patients would benefit most from repeated doses 4. In a separate cohort, Paaske and colleagues implemented a three-dose capsule regimen in high-risk patients, including those with fulminant CDI, patients expected to receive antibiotics in the week following FMT, and those aged 65 years or older with severe or antibiotic-refractory CDI 2. This change did not result in increased overall efficacy (70% 60%–78% vs. 67% 57%–76%). FMT is highly effective in the treatment of CDI, but real-world cure rates lag behind those of well-designed clinical trials. Ongoing development of optimal donor, recipient and administration protocols is needed. Repeated dosing increases the efficacy of FMT in CDI, and emerging evidence supports donor selection in this population. To advance the field, we must now define microbial factors associated with efficacy. Perhaps the future is a rationally designed microbial therapeutic, with a defined and reproducible mechanism of action. D. Bogatic: conceptualization, writing – original draft, writing – review and editing. S. P. Costello: conceptualization, writing – original draft, writing – review and editing. R. V. Bryant: conceptualization, writing – original draft, writing – review and editing. The authors have nothing to report. D. Bogatic has received research support from The Gutsy Group and BiomeBank. S.P. Costello is a shareholder of BiomeBank. R.V. Bryant has received grant/research support/speaker honoraria/advisory board fees from AbbVie, Ferring, Janssen, Shire, Takeda, GlaxoSmithKline, Bristol Myers Squibb, and Emerge Health; and is a shareholder in BiomeBank. This article is linked to Paaske et al paper. To view this article, visit https://doi.org/10.1111/apt.70395. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Bogatic et al. (Tue,) studied this question.