Dynamics of Bacterial and Viral Transmission in Experimental Microbiota Transplantation

Abstract

Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transplantation of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of fecal or cecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, fecal transplantation, and cecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored bacterial and viral populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transplanted control mice. While all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. This study provides valuable insights into microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transplantation in mouse models.