First Human Transmission of Dientamoeba fragilis via Fecal Microbiota Transplantation: A new argument for apathogenicity

Since 2014, fecal microbiota transplantation (FMT) has been the recommended treatment for recurrent Clostridioides difficile infections (rCDI), with success rates up to 85% and improved patient survival [1–5]. FMT aims to therapeutically modulate the recipient's gut microbiome. For safety reasons, donors undergo rigorous selection procedures, including multiple clinical and biological screenings, to minimize the risk of transmitting pathogens and potential diseases associated with gut microbiota [6]. Following this selection process, only 3-10% of candidates qualify as eligible intestinal microbiota donors, limiting the availability and accessibility of this proven beneficial treatment [7] [8]. Dientamoeba fragilis is an intestinal protozoan parasite belonging to the Trichomonadidae order even though it lacks flagella [9]. D. fragilis has been detected worldwide with prevalence rates ranging from 0.2% to 82%, and often exceeding 20% in molecular epidemiological studies [10]. However, its route of transmission remains poorly understood. The pathogenicity of D. fragilis remain debated, with limited evidence linking it to gastrointestinal symptoms such as diarrhea and abdominal pain [11]. FMT serves as a valuable and reliable model for studying the impact of controversial fecal microorganisms, providing direct exposure to donor gut microbiota in recipients. For example, Blastocystis hominis, another protist with debated pathogenicity, was removed from the donor exclusion list following a study by Teerver et al., which demonstrated no adverse consequences in recipients from B. hominis-positive donors [12]. As a result of this study, the 5th edition of the Guide to the Quality and Safety of Organs for Transplantation (EDQM, 2022) no longer lists B. hominis as an exclusion criterion for donors, unlike D. fragilis. The transmission and impact of D. fragilis during FMT, however, still require further investigation. To date, real-time PCR (RT-PCR) for D. fragilis is not part of routine donor screening at the Lausanne University Hospital, the only center in Switzerland performing FMT. The primary objective of our study was to assess the prevalence of D. fragilis in stool samples from FMT donors and their paired recipients, both before and after FMT, using RT-PCR. Additionally, we aimed to investigate whether the presence of D. fragilis affects the efficacy of FMT or is associated with adverse events post-FMT.