Persistence of a Transplanted Human Bacterial Gut Microbiome in Double Humanized BLT-mice

Humanized mice have fundamentally changed the study of human pathogens and disease. Humanized mice have a functional human immune system that can be used to model diseases that are otherwise difficult or impossible to study in standard lab mice or other models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans and there is a need for additional pre-clinical models to study the human microbiome. Therefore, we created double humanized mice that have both a human immune system and stable human-like microbiome. Surgery was performed on NSG mice to create bone-marrow, liver, thymus-humanized mice. The mice were then treated with broad spectrum antibiotics and then given fecal transplants with healthy human donor samples. Double humanized mice had unique 16S rRNA gene profiles based on the individual human donor sample that is transplanted. Importantly, the transplanted human-like microbiome was stable in the mice for the duration of the study up to 14.5 weeks post-transplant. In addition, the predicted metagenomes showed that double humanized mice have different predicted functional capacity than humanized mice that was more similar to the human donor samples.