Background

Fecal microbiota transplant (FMT) is recommended for patients with multiple recurrences of Clostridioides difficile infection (CDI) having failed antibiotic treatment [1]. FMT is associated with an 81-93% success rate dependent on route of instillation [2]. Evidence assessing factors contributing to successful transplantation remain sparse, but include avoidance of antibiotics post-FMT, absence of inflammatory bowel disease, and good bowel preparation. CDI-related hospitalization before FMT, inpatient FMT, and severe CDI are associated with increased risk of FMT failure [3].

Little is known about the effect of the mycobiota on FMT outcomes in patients with CDI. However, a recent analysis found that the fungal genera Saccharomyces, Aspergillus, and Penicillum were relatively more abundant in FMT responders post-FMT than in nonresponders [4]. At our institution, a Saccharomyces boulardii based probiotic is used for primary prophylaxis of hospital onset CDI. Here we describe the effect of incident S. boulardii administration in FMT recipients treated for recurrent Clostridioides difficile infection in a population at increased risk for poor response to FMT.

Methods

This is a five-year, retrospective cohort study assessing FMT success in patients with incident S. boulardii administration directly prior to and following FMT. Patients are included if they were aged 18 years or older and underwent FMT (colonoscopy with fecal transplant) while admitted to the institution between January 1, 2016 and December 31, 2020. The independent variable is a two-level categorical variable classifying patients as administered of Saccharomyces boulardii lyo CNCM I-745 (Florastor Daily Probiotic Supplement^®, Biocodex, Inc., Redwood City, CA, USA) for a minimum of two days prior to FMT and at least one dose following FMT verified by barcode administration records. The dependent variable of interest is a two-level categorical variable classifying patients as having failed FMT defined as evidence of diarrhea symptoms noted in patient medical record and a positive Clostridioides difficile stool test within the eight weeks following FMT.

All patients assessed were hospitalized for CDI management and underwent FMT while admitted. The dose of S. boulardii used at the institution is 500mg twice daily. S. boulardii is not approved for prevention of CDI or for use with FMT. All patients were administered frozen microbiota specimen (OpenBiome item: FMP250, Somerville, Massachusetts, US) via colonoscopy.

Baseline characteristics included patient age, gender, procedure date, time to failure, presence of North American pulsed-field gel electrophoresis type 1 (NAP1) strain, and continuation of antibiotics following FMT.

Fisher’s exact statistics was used to test for unadjusted associations between S. boulardii administration and the incidence of FMT success.

Results

The study included 41 patients who underwent FMT. FMT failed in five total patients (12.2%). Incident S. boulardii administration for at least two days prior to FMT and at least one dose after FMT occurred in 24 patients. More patients administered S. boulardii had antibiotics continued following FMT (p = 0.01). All other baseline characteristics were similar between groups. (Table 1) The FMT success rate observed for patients administered S. boulardii was 91.7% (22/24) versus 82.4% (14/17) in those not administered S. boulardii (p> 0.05). (Table 2) No patients with discontinuation of antibiotics and administration of S. boulardii prior to FMT experienced FMT failure.

Discussion

This study assesses the influence of Saccharomyces boulardii lyo CNCM I-745 administration on FMT response in a population at increased risk of FMT failure due to CDI-related hospitalization and inpatient FMT receipt. It was observed that patients administered S. boulardii had a higher numerical FMT response rate versus patients not administered S. boulardii, this did not achieve statistical significance. The analysis and case rate for FMT failure is small and limits our ability to detect a statistical difference. Additionally, this analysis failed to capture patients that may have developed symptoms of recurrent CDI not requiring rehospitalization or who sought medical treatment at an alternative facility.

The full extent of S. boulardii benefit present in this analysis may be masked by the high rate of antibiotic continuation present in the S. boulardii recipient group. Half of the patients administered S. boulardii had antibiotics continued following FMT. In comparison, only two patients (11%) not administered S. boulardii continued to receive antibiotics following FMT. S. boulardii is used at our facility to prevent CDI in patients on antibiotics, which is why a higher prevalence of antibiotic continuation is observed in the S. boulardii recipients.

Continuation of antibiotics immediately leading up to FMT and following FMT is a significant risk factor for FMT failure. [3-4] All FMT failures in the S. boulardii cohort occurred in patients with antibiotic continuation. In subgroup analysis of patients with antibiotic discontinuation, those with S. boulardii administration prior to and following FMT experienced a FMT success rate of 100% (12/12) compared to 80% (12/15) for those without S. boulardii administration. This suggests that there may be a beneficial effect on FMT success and CDI treatment from the administration of S. boulardii prior to and following FMT.

Conclusion

This is a small retrospective observation study that is strictly hypothesis generating. No statistical difference in FMT outcomes was detected in patients with incident S. boulardii administration. S. boulardii administration did not contribute to worse outcomes and may be associated with improved FMT outcomes. Further study is therefore warranted to further assess the role of S. boulardii in FMT administration for CDI treatment.

Acknowledgments

Financial Support

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This research was supported in part by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities. Potential conflicts of interest. The author reports no conflicts of interest relevant to this article.

Specific Author Contributions

EW- Substantial contributions to the conception and design of the work; analysis and interpretation of data; drafting, revising, and final approval of the version to be published.

Tables

References

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2. Cammarota G, Ianiro G, Gasbarrini A (2014) Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review. J Clin Gastroenterol 48: 693-702.
3. Tariq R, Hayat M, Pardi D, Khanna S (2021) Predictors of failure after fecal microbiota transplantation for recurrent Clostridioides difficile infection: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis 40: 1383-1392.
4. Zuo T, Wong SH, Cheung CP, Lam K, Lui R, et al. (2018) Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection. Nat Commun 9: 3663.