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Fecal microbiota transplantation (FMT) is widely used as a last resort treatment for Clostridioides difficile infection; it has also been demonstrated to be an effective treatment for other gastrointestinal disorders [1-3]. The increasing demand for FMT has led to the establishment of several fecal microbiota banks around the world to provide safe access to donor feces. Several reports have outlined FMT donor-screening criteria for minimizing the risk of infectious agent transmission [4-10]. A recent report on serious adverse effects associated with extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae transmission via FMT emphasizes the need for rigorous FMT donor screening [11]. Implementation of a standardized FMT donor screening protocol is important; however, some modifications to the protocol may be required when considering the local prevalence of infectious agents [8].
Many European and North American fecal microbiota banks have recently reported their donor screening outcomes, and these data have provided insights for establishing evidence-based FMT consensus reports [4-10,12]. However, there is a paucity of such reports from Asian fecal microbiota banks, despite there being numerous publications on FMT clinical outcomes [13, 14]. This report presents the donor screening outcomes from a fecal microbiota bank in Korea (Microbiotix Corporation, Seoul, Korea).
In November 2016, Microbiotix Corporation, a university hospital-affiliated startup company, founded a non-profit fecal microbiota bank in collaboration with physicians from various disciplines (laboratory medicine, gastroenterology, pulmonology, and infectious disease). This fecal microbiota banking project was approved by the Severance Hospital Institutional Review Board, Seoul, Korea (IRB No. 4-2016-0850). Donors were recruited through poster advertisements at the Yonsei University Health System starting August 2017. Individuals interested in fecal donation were invited for a two-stage donor-screening process (stage 1, clinical assessment; stage 2, laboratory tests) created based on the Korean Transfusion Guidelines and the European and American FMT donor screening protocols [4, 5, 9, 15].
A summary of the donor screening criteria is provided in Table 1. All donor candidates provided informed consent to participate in the study. An in-person clinical assessment (stage 1) was carried out to evaluate the donor candidates for general health and gastrointestinal conditions and for any risk factors for transmissible diseases. This process was performed by a nurse clinical research coordinator and was verified by a laboratory medicine specialist. At stage 2, donor candidates underwent serological/fecal screening, a urea breath test (UBT), and chest (posteroanterior) radiography to identify underlying health conditions and potentially transmissible pathogens. Although FMT is recognized as a safe and effective treatment with manageable adverse effects (e.g., bloating, cramping, and diarrhea), it is crucial to acknowledge previously reported adverse effects possibly associated with FMT [16, 17]. A previous study reported two cases of FMT-associated ESBL-producing Escherichia coli bacteremia in the United States, which led the US Food and Drug Administration to mandate additional screening against multidrug-resistant organisms (MDRO) [16]. Therefore, we rigorously screened for viral, bacterial, and protozoal pathogens to prevent potential pathogen transmission via FMT.
The qualification of 62 candidates to serve as potential FMT donors was assessed from August 2017 through June 2020 (Fig. 1). Forty-six (74%) candidates were excluded based on the pre-screening questionnaire responses. High body mass index (BMI; >25) was the most common reason for donor exclusion (16 individuals), followed by atopy, asthma, and allergy history (15 individuals). The remaining 16 candidates underwent serological/fecal screening, and four (25%) failed to meet laboratory test criteria. Of the donor candidates excluded at stage 2, three candidates (75%) had abnormal blood test results and one carried ESBL-producing Enterobacteriaceae. Overall, 12 candidates (19% of the initial donor candidate pool) qualified as FMT donors. Our study outcome was consistent with the donor qualification rates in earlier reports [6, 7, 9].
All fecal material from the qualified donors was processed into slurries and quarantined for one month to ensure that it passed the monthly re-qualification process. The re-qualification process involved the same clinical assessment and laboratory test stages as the initial screening process. After the re-qualification process, nine candidates (75%) did not meet the laboratory test criteria as they showed risks for infectious diseases (five with MDRO, four with Helicobacter pylori, one with enteric bacteria, and one with Blastocystis hominis colonization; one candidate had a positive UBT result) (Fig. 1). Finally, only three candidates (5% of the donor candidate pool) were eligible to donate feces. These results suggest that continuous donor recruitment is necessary to prevent a shortage of donors and FMT materials. Earlier reports demonstrated similar donor-screening outcomes, with several candidate donors failing to meet the re-qualification criteria [6, 9]. A high percentage of donor failure on monthly re-qualification screening of FMT donors emphasizes that such screening could prevent the potential transmission of infectious materials through FMT by identifying risk factors not detected in the initial screening process.
Regular screening of FMT donors is crucial, as it serves as an ongoing safety control measure. H. pylori carriage was not a concern for donor candidate disqualification during the initial donor screening. However, four of the initially qualified donors, accounting for 33% of the qualified donors, were excluded owing to H. pylori carriage during the re-qualification process. Owing to the high prevalence of potentially asymptomatic H. pylori carriers in the donor pool, our center added UBT to the ongoing screening process in May 2019. Although nested PCR for H. pylori detection was used due to its high sensitivity and specificity, possible degradation of H. pylori DNA may have contributed to a lower rate of positive test results [18]. UBT, the gold standard for H. pylori diagnosis, was added to the existing donor screening protocol as an additional method for identifying asymptomatic H. pylori carriers [18-20]. A larger sample size may be required to obtain a better representation of the healthy population in Korea and determine whether high H. pylori prevalence could be a generalizable criterion for donor exclusion in Asian fecal microbiota banks.
To the best of our knowledge, this is the first report to outline the donor screening process and outcomes at a fecal microbiota bank in Asia. After establishing donor screening criteria based on pre-existing protocols and consensus reports, the FMT donor qualification rate was 19%. High BMI (>25; N=16) and abnormal serological test results (increased total bilirubin level (2.2 mg/dL) and positive antinuclear antibody test; N=4) were the major criteria for donor exclusion based on clinical assessment and laboratory tests, respectively. A monthly donor re-qualification process contributed to a high overall donor exclusion rate. It resulted in identifying new risk factors, including carriage of infectious agents (H. pylori and B. hominis) and abnormal lipase and amylase levels, that were not considered during the initial donor screening process for FMT.
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