Researchers construct most complex, complete synthetic microbiome

Key studies in the last decade have shown that the gut microbiome, the collection of hundreds of bacterial species that live in the human digestive system, influences neural development, response to cancer immunotherapies, and other aspects of health. But these communities are complex and without systematic ways to study the constituents, the exact cells and molecules linked with certain diseases remain a mystery.

Stanford University researchers have built the most complex and well-defined synthetic microbiome, creating a community of over 100 bacterial species that was successfully transplanted into mice. The ability to add, remove, and edit individual species will allow scientists to better understand the links between the microbiome and health, and eventually develop first-in-class microbiome therapies.

Many key microbiome studies have been done using fecal transplants, which introduce the entire, natural microbiome from one organism to another. While scientists routinely silence a gene or remove a protein from a specific cell or even an entire mouse, there is no such set of tools to remove or modify one species among the hundreds in a given fecal sample.

“So much of what we know about biology, we wouldn’t know if it weren’t for the ability to manipulate complex biological systems piecewise,” said Michael Fischbach, Institute Scholar at Sarafan ChEM-H and corresponding author on the study, published in Cell on Sept. 6.

Fischbach, who is an associate professor of bioengineering and of microbiology and immunology, and others saw one solution: Build a microbiome from scratch by growing individually and then mixing its constituent bacteria.

Building the ark

Each cell in the microbiome occupies a specific functional niche, performing reactions that break down and build up molecules. To build a microbiome, the team had to ensure that the final mixture was not only stable, maintaining a balance without any single species overpowering the rest, but also functional, performing all the actions of a complete, natural microbiome. Selecting species to include in their synthetic community was also difficult given the natural variation across individuals; two people selected at random share less than half of their microbial genes.

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