Fecal virus-like particles are sufficient to reduce necrotizing enterocolitis

Simone Margaard Offersen, Xiaotian Mao, Malene Roed Spiegelhauer, Frej Larsen, Viktoria Rose Li, Dennis Sandris Nielsen, Lise Aunsholt, Thomas Thymann, Anders Brunse*

*Corresponding author for this work

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Abstract

Fecal filtrate transfer (FFT) is emerging as a safer alternative to traditional fecal microbiota transplantation (FMT)–particularly in the context of necrotizing enterocolitis (NEC), a severe gastrointestinal condition affecting preterm infants. Using a preterm piglet model, FFT has demonstrated superiority over FMT in safety and NEC prevention. Since FFT is virtually devoid of bacteria, prokaryotic viruses (bacteriophages) are assumed to mediate the beneficial effects. However, this assumption remains unproven. To address this gap, we separated virus-like particles (30 kDa to 0.45 µm) of donor feces from the residual postbiotic fluid. We then compared clinical and gut microbiota responses to these fractions with the parent FFT solution after transferring them to NEC-susceptible preterm piglets. Virome transfer was equally effective as FFT in reducing the severity of NEC-like pathology. The bacterial compositional data corroborated clinical findings as virome transfer reduced the relative abundance of several NEC-associated pathogens e.g. Klebsiella pneumoniae and Clostridium perfringens. Virome transfer diversified gut viral communities with concomitant constraining effects on the bacterial composition. Unexpectedly, virome transfer, but not residual postbiotic fluid, led to earlier diarrhea. While diarrhea may be a minor concern in human infants, future work should identify ways of eliminating this side effect without losing treatment efficacy.

Original languageEnglish
Article number2392876
JournalGut Microbes
Volume16
Issue number1
Number of pages22
ISSN1949-0976
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.

Keywords

  • bacteriophages
  • diarrhea
  • fecal microbiota transplantation
  • Fecal virome transplantation
  • necrotizing enterocolitis
  • preterm

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