Microflora in a test tube
Numerous studies prove that the gut microbiome affects the development of the nervous system, the response to cancer immunotherapy and other aspects of health. But these bacterial communities are complex, and without systematization, it is impossible to assess the impact of individual cells or molecules on human health.
Researchers from Stanford University have created the most complex synthetic microbiome to date – a community of more than 100 species of bacteria – and successfully transplanted it into mice. The ability to add, remove and edit individual species will allow scientists to better understand the links between intestinal microflora and health and eventually develop new treatments based on manipulation of the microbiome.
Usually microbiome studies are carried out using fecal transplants, which transfer the entire natural microbiome from one organism to another. It is impossible to remove or modify one of the hundreds of bacterial species to assess its effect on the body using the available tools. Michael Fischbach and his colleagues decided to create a microbiome from scratch, growing individually and then mixing the bacteria that make it up.
Each cell in the microbiome occupies a specific functional niche, performing reactions that break down and accumulate molecules. To create a microbiome, it is necessary to make sure that the final mixture will not only be stable, maintaining a balance without suppressing some species by others, but also functional, performing all the actions of a full-fledged natural microbiome. The selection of species to include them in the synthetic community was also difficult, given the natural variability between individuals; for example, two randomly selected individuals carry less than half of the same bacteria.
The researchers decided to create their colony of the most common bacteria and turned to the Human Microbiome Project (HMP) of the National Institutes of Health to sequence the complete microbial genomes of more than 300 adults. They selected more than 100 strains of bacteria that were present in at least 20% of the people from the HMP database. By adding several species needed for some follow-up studies, the group obtained 104 strains. These bacteria were grown in separate cups, and then placed in one combined culture to form a single community (human community one, hCom1).
The strains in the synthetic microbiome co-existed stably in vitro. To test whether a new colony would take root in the animal's intestines, the researchers injected hCom1 into mice deprived of intestinal microflora. hCom1 was surprisingly stable, with 98% of the constituent species colonizing the intestines of these mice, and the relative abundance of each species remained constant for two months.
Next, it was necessary to make sure that all the vital functions of the microbiome would be performed. The authors relied on the theory of colonization resistance, according to which any bacterium, once introduced into an existing colony, will survive only if it fills an unoccupied niche. By introducing a complete microbiome in the form of a sample of human feces into the hCom1 colony and tracking any new species that settle there, the researchers could create a more complete community.
It is noteworthy that hCom1 was kept almost independently, and only about 10% of the bacteria in the final community were isolated from the fecal transplant.
The result was a new community of 119 strains, called hCom2.
To demonstrate the usefulness of the synthetic microbiome, mice colonized with hCom2 were injected with a sample of E. coli. These mice, like mice with a natural microbiome, resisted infection.
Previous studies have shown that a healthy natural microbiome fights E. coli, but Fischbach and his colleagues are going one step further by eliminating or modifying certain strains to determine which ones specifically provide protection against it. They have already discovered several key bacteria and plan to conduct further research to narrow down the most important species.
The authors suggest that the method of creating a microbiome from scratch will make it possible to treat or prevent various diseases, including autoimmune and oncological.
Article by A.Cheng et al. Design, construction, and in vivo augmentation of a complex gut microbiome is published in the journal Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on materials from Stanford University: Stanford researchers construct most complex, complete synthetic microbiome.