The development of DNA sequencing technologies has created a large amount of data on microbes that live with human hosts. Analysis of this data has led to an understanding of the links between the human microbiome, pathogen defense, food digestion and even human behavior. Before the development of mass DNA sequencing technologies, we could analyze a handful of human microbes that were grown on Petri dishes. However, we now know that the human microbiome consists of hundreds, if not thousands, of microbes. In fact, illuminating the number of microbes did not just provide academic pieces of information, but also translated into medically valuable knowledge. A striking example of the medical translation could be seen in the treatment of deadly Clostridium difficile infection; thanks to the developments in microbiome research we know that transplanting feces from a healthy donor often cures C. difficile infection. According to Dr. Alice Cheng from Stanford University, the fecal microbiome transplant treatment of C. difficile infections works shockingly well. Although sequencing technology has opened the door to a vast array of information, there are still limitations. These include a large number of microbes present in the microbiome, particularly those that are unculturable, as well as challenges in controlling confounding factors such as human lifestyle differences, including diet. These can make it difficult to effectively translate human microbiome research into the medical setting. An approach to overcome these confounding factors has been using animal models, particularly mice. However, until recently, only up to 20 human microbes had ever been inoculated into mice. A recent article in the New York Times highlighted the study of Dr. Cheng (2022) to increase the number of microbes used in mouse models. Dr. Cheng and colleagues identified 166 bacterial species that were ubiquitous in the majority of healthy people and could supply 104 out of 166 species. Then, the research group inoculated the bacterial cocktail of 104 species into germ-free (GF) mice. According to their findings, all 104 species established a stable ecosystem in the mice, simulating the structure in the human gut, and stayed that way throughout the study. To test the resilience of this synthetic human microbiome in mice, the group transplanted the experimental mice with human feces. The results illustrated that only 7 out of the 104 species disappeared due to the transplant perturbation, highlighting the stability of the synthetic community. Next, the research group tested how well the mice with synthetic gut microbiota resisted E. coli infection. Here, they observed that resilience to E. coli was similar to that of resilience to the human stool transplant. The synthetic bacterial cocktail by Cheng et al. (2022) was alone enough to raise healthy levels of digestive fluids in the mouse gut, and to develop full-fledged immunity. The research group has already started filtering out certain microbes from the synthetic community in order to better understand how individual microbes work within the community. Through designing novel experiments with this synthetic microbiome, Dr. Cheng aims to understand how microbes that help our intestines to absorb fat from food are linked to obesity. Overall, the creation of this large and diverse synthetic microbiome provides a valuable resource to help refine our understanding of the mechanisms of the human microbiome.
Transplanting mice with synthetic human microbiota
13 September 2022by Barış Özdinç0