Abstract
Fecal microbiota transplantation (FMT) is an effective tool for treating Clostridium difficile infection in the setting of dysbiosis of the intestinal microbiome. FMT for other forms of human disorders linked to dysbiosis have been less effective. The fecal microbiota contains a high density of virus-like particles (VLP), up to 90% of which are bacteriophages, thought to have a role in regulating gut bacterial populations. We hypothesized that transplantation of the phage-containing fecal VLP fraction may reduce bacterial density in the dysbiotic setting of small intestinal bacterial overgrowth (SIBO). In an experiment using fecal transplantation, we compared the effect of the fecal VLP fraction (bacteria removed) against “Whole” FMT (bacteria intact) on the ileal microbiome. Recipients were either treated with a 30-day high-fat diet (HFD) as a model of dysbiosis to induce SIBO or were on a standard diet (SD). We observed that transplantation of fecal VLPs from donors on a HFD was sufficient to alter the ileal microbiota, but the effect was dependent on diet of the recipient. In recipients on a HFD, ileal bacterial density was reduced. In recipients on a SD, the ileal microbiome transitioned toward the composition associated with a HFD. In both recipient groups, transplantation of fecal VLP fraction alone produced the same outcome as whole FMT. Neither treatment altered expression of antimicrobial peptides. These findings demonstrated a potential role of VLPs, likely phages, for modifying the gut microbiome during dysbiosis.
Highlights
During fecal microbiota transplantation (FMT), a large population of virus-like particles (VLPs) are transferred into the gastrointestinal tract of the recipient
These findings based on the “Phage-on-Tap” protocol by Bonilla et al (2016) demonstrated that a combination of centrifugation and size filtration could effectively fractionate the fecal microbiota into a sub-bacterial fraction, which removes bacteria but retains VLPs, and a sub-viral fraction, which further removes VLPs
Following induction of Small intestinal bacterial overgrowth (SIBO) using a 30-day highfat diet (HFD) model, we found that bacterial density, as estimated by the relative quantitation of 16s rRNA, was significantly reduced in HFD recipients receiving either VLP or Fecal microbiota transplantation (FMT) transplants, as compared to HFD-phosphate-buffered saline (PBS) control mice
Summary
During fecal microbiota transplantation (FMT), a large population of virus-like particles (VLPs) are transferred into the gastrointestinal tract of the recipient. SIBO may be induced by a variety of disruptors of the gut including a highfat diet (HFD) (Tomas et al, 2016) and is commonly treated with antibiotic therapy. Strain-specific phage therapy has been used to kill a targeted bacterial pathogen at a specific site of infection (Lin et al, 2017). It is not known whether a diverse population of phages, such as that represented in the fecal VLP fraction could be used to reduce colonization by a diverse population of resident bacteria across a large surface area such as the small intestinal mucosa
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