Phage-microbe dynamics after sterile faecal filtrate transplantation in individuals with metabolic syndrome: a double-blind, randomised, placebo-controlled clinical trial assessing efficacy and safety

• Published in: Nature communications Vol. 14; no. 1; pp. 5600 - 16
• Main Authors: Wortelboer, Koen, de Jonge, Patrick A., Scheithauer, Torsten P. M., Attaye, Ilias, Kemper, E. Marleen, Nieuwdorp, Max, Herrema, Hilde
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.09.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 38/22; 38/23; 631/326/1321; 631/326/41/2142; 692/163/2743/2037; 692/4020/1503/2745; Clinical trials; Composition; Digestive system; Double-blind studies; Filtrate; Gastrointestinal tract; Glucose; Glucose metabolism; Glucose tolerance; Humanities and Social Sciences; Immunological tolerance; Intestinal microflora; Metabolic disorders; Metabolic syndrome; Microbial activity; Microbiomes; Microbiota; Microorganisms; multidisciplinary; Phages; Placebos; Safety; Science; Science (multidisciplinary); Transplantation; Virions
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41329-z

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. Bacteriophages (phages) can modify the gut microbiome to benefit human health. Here, the authors report the results of a double blind, randomized, placebo-controlled trial, showing that faecal filtrate transplantation (FFT), containing phages from lean healthy donors, is safe and improves glycemic variability in patients with metabolic syndrome, while shifting the gut phage composition.