Fecal Virome Transplantation (FVT) from healthy humans remodels the gut bacteriome and virome and reduces metabolic syndrome in mice

Abstract

The gut microbiome regulates host processes, including metabolism, and comprises viruses, archaea, fungi, protists, and bacteria. However, previous studies have primarily focused on the bacterial components of the microbiome. This study conducted cross-infection experiments by fecal virome transplantation (FVT) to examine the impact of virus-like particles (VLPs) from normal-weight individuals on bacterial and virome diversity and metabolic changes in mice. We found that FVT significantly restored glucose tolerance in mice, even though they were maintained on a high-fat diet (HFD). Shotgun metagenomics and 16s profiling confirmed that FVT shifted gut bacterial and viral richness and diversity, resulting in several differentially abundant bacteria and phages. The abundance of Akkermansia muciniphila decreased significantly after FVT, remained low until the end of the experiment (week 17), and correlated with a decreased glucose tolerance. On the other hand, there was a significant increase in Allobaculum and Coprococcus at weeks 10 and 17 post-FVT. The abundance of Allobaculum correlated with an increased glucose tolerance, indicating a beneficial hypoglycemic effect on the mice inoculated with VLPs. We also found an increased virome diversity at week 17, while richness was similar to the one before FVT. The study provides a proof of concept for the efficacy of FVT from human donors to mice, improving glucose tolerance by altering the gut microbiota and virome despite maintaining a HFD. Overall, our results suggest that trans-kingdom interactions between the virome and bacteriome from humans could be translated to mice as a study model.