Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection
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BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (CDI). However, transferring undefined living bacteria entails uncontrollable risks for infectious and metabolic or malignant diseases, particularly in immunocompromised patients. We investigated whether sterile fecal filtrates (containing bacterial debris, proteins, antimicrobial compounds, metabolic products, and oligonucleotides/DNA), rather than intact microorganisms, are effective in patients with CDI. METHODS: We performed a clinical case series to investigate the effects of fecal filtrate transfer (FFT) in 5 patients with symptomatic chronic-relapsing CDI at the Department of Internal Medicine I at the University Hospital Schleswig-Holstein (Kiel, Germany). Patients were followed up for at least 6 months and for up to 33 months. Stool was collected from 5 donors selected by the patients, and fully characterized according to FMT standards. Stool was sterile-filtered to remove small particles and bacteria; the filtrate was transferred to patients in a single administration via nasojejunal tube. Fecal samples were collected from patients before and at 1 week and 6 weeks after FFT. Microbiome, virome, and proteome profiles of donors and patients were compared. RESULTS: In all 5 patients, FFT restored normal stool habits and eliminated symptoms of CDI for a minimum period of 6 months. Proteome analyses of selected FFT filtrates showed no obvious protein candidates associated with therapeutic efficacy. 16S ribosomal RNA gene sequencing detected diverse bacterial DNA signatures in the filtrates. Analysis of virus-like particles from a filtrate found to reduce symptoms of CDI showed a complex signature of bacteriophages. Bacterial phylogeny and virome profile analyses of fecal samples from recipients indicated longitudinal changes in microbial and viral community structures after FFT. CONCLUSIONS: A preliminary investigation of 5 patients with CDI shows that transfer of sterile filtrates from donor stool (FFT), rather than fecal microbiota, can be sufficient to restore normal stool habits and eliminate symptoms. This finding indicates that bacterial components, metabolites, or bacteriophages mediate many of the effects of FMT, and that FFT might be an alternative approach, particularly for immunocompromised patients.
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Following successful treatment of C. difficile infection by FFT transplantation, the gut microbiota of a patient with loss of renal function resembled that of the faecal donor with remarkable elimination of Proteobacteria, which had dominated before FFT.
“Following successful treatment of C. difficile infection by FFT transplantation, the gut microbiota of a patient with loss of renal function resembled that of the faecal donor with remarkable elimination of Proteobacteria, which had dominated before FFT226.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [226]
The risk of secondary infection may be lower with FFT than with FMT, as FFT does not involve transfer of live bacteria.
“The risk of secondary infection may be lower with FFT than with FMT, as FFT does not involve the transfer of live bacteria226.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [226]
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- Authors
- Ott, S. J., Waetzig, G. H., Rehman, A., Moltzau-Anderson, J., Bharti, R., Grasis, J. A., Cassidy, L., Tholey, A., Fickenscher, H., Seegert, D., Rosenstiel, P., & Schreiber, S.
- Affiliations
- University Hospital Schleswig-Holstein (DE)
- Conaris (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- San Diego State University (US)
- Corresponding author
- Schreiber, Stefan
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 152
- Issue
- 4
- Pages
- 799-811.e7
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2550586225
- Cited by
- 695
- References
- 54
- Citations by year
- 2026: 37 · 2025: 64 · 2024: 83 · 2023: 73 · 2022: 85 · 2021: 96 · 2020: 65 · 2019: 82 · 2018: 69 · 2017: 38 · 2016: 1
- FWCI
- 58.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Gastroenterology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (CRC 1182)
- Exzellenzclusters Entzündungsforschung
- Topics
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- fecal microbiota transplantation, Clostridium difficile infection, recurrent Clostridium difficile infection, sterile filtration, bacteriophages, virome, microbiome, immunocompromised patients, bacterial community structure
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Aged, Enterocolitis, Pseudomembranous, Female, Filtration, Humans, Male, Middle Aged, Recurrence, Sterilization, Clostridioides difficile, Proteome, Gastrointestinal Tract
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