Cited by 697Clostridium difficile and Clostridium perfringens researchGut microbiota and healthGastrointestinal motility and disorders

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Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection

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Ott, Stephan J., Waetzig, Georg H., Rehman, Ateequr, Moltzau-Anderson, Jacqueline, Bharti, Richa, Grasis, Juris A., Cassidy, Liam, Tholey, Andreas, Fickenscher, Helmut, Seegert, Dirk, Rosenstiel, Philip, Schreiber, Stefan·2017·Gastroenterology

DOI 10.1053/j.gastro.2016.11.010

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Abstract

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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Additional file 3 of Repeated inoculation with rumen fluid accelerates the rumen bacterial transition with no benefit on production performance in postpartum Holstein dairy cows
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Additional file 1 of Repeated inoculation with rumen fluid accelerates the rumen bacterial transition with no benefit on production performance in postpartum Holstein dairy cows
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Additional file 4 of Strain engraftment competition and functional augmentation in a multi-donor fecal microbiota transplantation trial for obesity
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Additional file 1 of Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis
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Additional file 1 of Fecal microbiota transplantation alters gut phage communities in a clinical trial for obesity
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Additional file 2 of Fecal microbiota transplantation alters gut phage communities in a clinical trial for obesity
Zuppi, M., Vatanen, T., Wilson, B. C., Golovina, E., Portlock, T., Cutfield, W. S., Vickers, M. H., & O’Sullivan, J. M. (2024) · Figshare · doi:10.6084/m9.figshare.26195886
Additional file 3 of Fecal microbiota transplantation alters gut phage communities in a clinical trial for obesity
Zuppi, M., Vatanen, T., Wilson, B. C., Golovina, E., Portlock, T., Cutfield, W. S., Vickers, M. H., & O’Sullivan, J. M. (2024) · Figshare · doi:10.6084/m9.figshare.26744621
Additional file 4 of Repeated inoculation with rumen fluid accelerates the rumen bacterial transition with no benefit on production performance in postpartum Holstein dairy cows
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Additional file 5 of Repeated inoculation with rumen fluid accelerates the rumen bacterial transition with no benefit on production performance in postpartum Holstein dairy cows
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Additional file 2 of Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis
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Additional file 7 of Repeated inoculation with rumen fluid accelerates the rumen bacterial transition with no benefit on production performance in postpartum Holstein dairy cows
Kong, F., Wang, F., Zhang, Y., Wang, S., Wang, W., & Li, S. (2024) · Figshare · doi:10.6084/m9.figshare.26676725
Additional file 8 of Repeated inoculation with rumen fluid accelerates the rumen bacterial transition with no benefit on production performance in postpartum Holstein dairy cows
Kong, F., Wang, F., Zhang, Y., Wang, S., Wang, W., & Li, S. (2024) · Figshare · doi:10.6084/m9.figshare.26676728
Additional file 6 of Repeated inoculation with rumen fluid accelerates the rumen bacterial transition with no benefit on production performance in postpartum Holstein dairy cows
Kong, F., Wang, F., Zhang, Y., Wang, S., Wang, W., & Li, S. (2024) · Figshare · doi:10.6084/m9.figshare.26676722
Additional file 5 of Strain engraftment competition and functional augmentation in a multi-donor fecal microbiota transplantation trial for obesity
Wilson, B. C., Vatanen, T., Jayasinghe, T. N., Leong, K. S. W., Derraik, J. G., Albert, B. B., Chiavaroli, V., Svirskis, D. M., Beck, K. L., Conlon, C. A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14594454
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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: Ott, Stephan J.
Waetzig, Georg H.
Rehman, Ateequr
Bharti, Richa
Grasis, Juris A.
Cassidy, Liam
Tholey, Andreas
Rosenstiel, Philip
Schreiber, Stefan
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2017-03
Volume: 152
Issue: 4
Pages: 799-811.e7
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2016.11.010
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
FWCI: 58.44
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
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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Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection

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