open access publication

Article, 2024

Reproducible chemostat cultures to minimize eukaryotic viruses from fecal transplant material

iScience, ISSN 2589-0042, Page 110460, 10.1016/j.isci.2024.110460

Contributors

Adamberg, Signe 0000-0002-8198-1618 [1] Rasmussen, Torben Sølbeck 0000-0002-9907-8953 [2] Larsen, Sabina Brigitte [2] Mao, Xiaotian 0000-0001-9425-683X [1] Nielsen, Dennis Sandris 0000-0001-8121-1114 [2] Adamberg, Kaarel 0000-0002-7203-925X (Corresponding author) [1]

Affiliations

  1. [1] Tallinn University of Technology
  2. [NORA names: Estonia; Europe, EU; OECD];
  3. [2] University of Copenhagen
  4. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD]

Abstract

Recent studies indicate an important role of bacteriophages for successful fecal microbiota transplantation (FMT). However, wider clinical applications of FMT are hampered by to donor variability and concerns of infection risks by bacteria and human viruses. To overcome these challenges, mouse cecal and human fecal material were propagated in a chemostat fermentation setup supporting multiplication of bacteria, and phages, whilst propagation of eukaryotic viruses will be prevented in the absence of eukaryotic host cells. The results showed decrease of the median relative abundance of viral contigs of classified eukaryotic viruses below 0.01 %. The corresponding virome profiles showed dilution rate dependency, a reproducibility between biological replicates, and maintained high diversity regarding both the human and mouse inoculum. This proof-of-concept cultivation approach may constitute the first step of developing novel therapeutic tools with high reproducibility and with low risk of infection from the donor material to target gut-related diseases.

Keywords

absence, abundance, applications, approach, bacteria, bacteriophage, biological replicates, cells, chemostat, chemostat cultures, clinical application, concerns, contigs, cultivation, cultivation approach, culture, decrease, dependence, dilution, disease, diversity, donor, donor material, donor variability, eukaryotic host cells, eukaryotic viruses, fecal material, fecal microbiota transplantation, fermentation setups, gut-related diseases, high diversity, host cells, human fecal material, human viruses, infection, infection risk, inoculum, low risk, low risk of infection, materials, median relative abundance, mice, microbiota transplantation, multiplication, multiplication of bacteria, phage, profile, propagation, rate dependence, relative abundance, replication, reproducibility, results, risk, risk of infection, setup, study, therapeutic tool, tools, transplant material, transplantation, variables, viral contigs, virome, virome profiles, virus

Funders

  • Lundbeck Foundation
  • Novo Nordisk Foundation
  • Ministry of Education and Research

Data Provider: Digital Science