Researchers from Harvard University have successfully taken the first steps in creating a synthetic microbiome. Using signaling between Salmonella Typhimurium and E. coli, the team was able to promote a new “genetic signal-transmission system” in mice.

A cluster of E. coli, a common species of gut bacteria.

With the hope of inducing interspecies bacterial communication, the researchers manipulated the bacterial signaling method of quorum sensing where bacteria receive and send signaling molecules in order to gauge their population density, performing a group behavior after reaching a certain threshold. By using the variant acyl-HSL quorum sensing, a version absent in mammals, the researchers were able to assess the feasibility of using a signaling system nonnative to its host.

In order to see if the two bacterial species successfully communicated, the researchers introduced both a signaler circuit and a responder circuit into the mice. The signaler circuit, put into Salmonella Typhimurium, contained a gene called luxI that, when turned on by a molecule called ATC, produced a quorum signaling molecule. This molecule was received by the bacteria with the responder circuit, E. coli, triggering a cro gene. This gene then turned on a LacZ gene, which caused the bacteria to turn blue when plated with special agar, and another cro gene, creating a loop that continuously activated the LacZ gene. This served as an indicator, as a blue glow would illustrate if the interspecies communication and the E.coli’s “memory” of it were successful.

After the mice were given the two edited strains of bacteria and placed in a container with ATC-infused water for two days, the researchers analyzed their fecal samples. They found that all of them turned blue, indicating that the genetically engineered signaling system was successful: the E. coli received and remembered a signal from Salmonella Typhimurium in response to an environmental factor. This effective engineered communication, as the Director of Harvard’s Wyss Institute for Biologically Inspired Engineering puts it, is a major step forward in “engineer[ing] intestinal microbes for the better while appreciating that they function as part of a complex community”.

With the basic principles of a synthetic microbiome a success, the researchers now want to experiment with new bacterial species and signaling molecules, bringing them closer towards their ultimate goal of engineering a gut microbiome that can perform tasks ranging from improving digestion to curing diseases. As the “next frontier in medicine [and] wellness,” the microbiome will no doubt be a key pillar of medicinal research for decades to come.