TY - JOUR
T1 - Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome
T2 - a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety
AU - Wortelboer, Koen
AU - de Jonge, Patrick A.
AU - Scheithauer, Torsten P. M.
AU - Attaye, Ilias
AU - Kemper, E. Marleen
AU - Nieuwdorp, Max
AU - Herrema, Hilde
N1 - Funding Information: We want to thank Aline Fenneman, Klaartje de Bruin and Melanie Benard for their help with stool donor recruitment and screening. In addition, we thank Veera Houttu, Ulrika Boulund, Kim Dzobo and Torsten Scheithauer for performing the randomisation to guarantee blinding of the investigator and volunteer. We would also like to thank Ana Gerós, Yannick van Schajik and Stephanie Handana for their help in setting up the faecal filtrate production and optimisation. We are grateful for the help of the gastroenterology department of the Amsterdam UMC, location AMC, for their support with the Cortrak®2 enteral access system. We also like to acknowledge the Microbiota Centre Amsterdam for their help with the DNA isolation of the faecal samples and the Genomics core of the Amsterdam UMC, location AMC, for their advice on the whole genome shotgun sequencing. Finally, we are most grateful for the volunteers who participated in this clinical pilot study. Researchers were supported by various grants. K.W. was supported by a Novo Nordisk Foundation CAMIT grant 2018 (28232) to M.N. and a Diabetes II Breakthrough grant (459001008) to H.H.; P.A.dJ. and T.P.M.S. were supported by DDRF Senior fellowship (2019.82.004) to H.H.; I.A. was supported through a Le Ducq consortium grant (17CVD01) to M.N.; M.N. was supported by a personal ZONMW-VICI grant 2020 (09150182010020) and a Le Ducq consortium grant (17CVD01). H.H. was supported by a Senior Fellowship of the Dutch Diabetes Research Foundation (2019.82.004). The funders had no role in the study design, the collection, analysis and interpretation of data, the writing of the report and the decision to submit the article for publication. Funding Information: Patients were involved in the assessment of the grant proposals for this study by the Dutch Diabetes Research Foundation (Diabetes II Breakthrough grant (459001008) and Senior Fellowship (2019.82.004)). Moreover, the patient panel advised on the patient burden of the clinical study. In addition, patients were involved in the ethical approval of this study (as part of the ethics committee). Once the trial results became available, participants were informed of the results with a letter suitable for a non-specialist audience. Publisher Copyright: © 2023, Springer Nature Limited.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Bacteriophages (phages) are bacterial viruses that have been shown to shape microbial communities. Previous studies have shown that faecal virome transplantation can decrease weight gain and normalize blood glucose tolerance in diet-induced obese mice. Therefore, we performed a double-blind, randomised, placebo-controlled pilot study in which 24 individuals with metabolic syndrome were randomised to a faecal filtrate transplantation (FFT) from a lean healthy donor (n = 12) or placebo (n = 12). The primary outcome, change in glucose metabolism, and secondary outcomes, safety and longitudinal changes within the intestinal bacteriome and phageome, were assessed from baseline up to 28 days. All 24 included subjects completed the study and are included in the analyses. While the overall changes in glucose metabolism are not significantly different between both groups, the FFT is well-tolerated and without any serious adverse events. The phage virion composition is significantly altered two days after FFT as compared to placebo, which coincides with more virulent phage-microbe interactions. In conclusion, we provide evidence that gut phages can be safely administered to transiently alter the gut microbiota of recipients.
AB - Bacteriophages (phages) are bacterial viruses that have been shown to shape microbial communities. Previous studies have shown that faecal virome transplantation can decrease weight gain and normalize blood glucose tolerance in diet-induced obese mice. Therefore, we performed a double-blind, randomised, placebo-controlled pilot study in which 24 individuals with metabolic syndrome were randomised to a faecal filtrate transplantation (FFT) from a lean healthy donor (n = 12) or placebo (n = 12). The primary outcome, change in glucose metabolism, and secondary outcomes, safety and longitudinal changes within the intestinal bacteriome and phageome, were assessed from baseline up to 28 days. All 24 included subjects completed the study and are included in the analyses. While the overall changes in glucose metabolism are not significantly different between both groups, the FFT is well-tolerated and without any serious adverse events. The phage virion composition is significantly altered two days after FFT as compared to placebo, which coincides with more virulent phage-microbe interactions. In conclusion, we provide evidence that gut phages can be safely administered to transiently alter the gut microbiota of recipients.
UR - http://www.scopus.com/inward/record.url?scp=85170658742&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-023-41329-z
DO - https://doi.org/10.1038/s41467-023-41329-z
M3 - Article
C2 - 37699894
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5600
ER -