Abstract
Background
Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases.
Methods
We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1–3 years), combining culture methods and faecal metagenomics.
Results
Based on MDR culture (n = 87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 3 weeks after FMT). Metagenomic sequencing of patient stool samples (n = 63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n = 11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n = 22 patients), the recipients’ resistomes are still donor-like, suggesting the effect of FMT may last for years.
Conclusions
Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes.
Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases.
Methods
We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1–3 years), combining culture methods and faecal metagenomics.
Results
Based on MDR culture (n = 87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 3 weeks after FMT). Metagenomic sequencing of patient stool samples (n = 63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n = 11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n = 22 patients), the recipients’ resistomes are still donor-like, suggesting the effect of FMT may last for years.
Conclusions
Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes.
| Original language | English |
|---|---|
| Article number | 37 |
| Journal | Genome Medicine |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 28 Feb 2024 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© The Author(s) 2024.
Funding
We wish to express our gratitude to Eric K.L. Berssenbrugge and Ingrid M.G.J. Sanders from the Experimental Bacteriology group at the LUMC for culturing the MDR bacteria. We thank Prof. Dr. Hein W. Verspaget of the Netherlands Donor Feces Bank for continuous support and supervision. Also, our thanks go to GenomeScan B.V. for providing the DNA sequencing. Finally, we thank the Experimental Bacteriology group and the Center for Microbiome Analyses and Therapeutics of the LUMC for fruitful work discussions, and in particular Dr. Wiep Klaas Smits for feedback on the manuscript. The Netherlands Donor Feces Bank have received an unrestricted research grant from Vedanta Biosciences.
| Funders | Funder number |
|---|---|
| Netherlands Donor Feces Bank | |
| Vedanta Biosciences | |
| Leids Universitair Medisch Centrum |
Keywords
- Antibiotic resistance
- C. diff
- Faecal microbiota transplantation
- MDRO