MIT researchers hack common gut bacteria

Chuck Bednar for – @BednarChuck

Synthetic biologists at the Massachusetts Institute of Technology (MIT) have demonstrated for the first time that they are able to hack one of the most common types of gut bacteria. This is being hailed as a breakthrough that could allow them to ultimately be used to deliver drugs.

Writing in Thursday’s edition of the journal Cell Systems, lead investigators Timothy K. Lu and Christopher Voigt reported that they were able to take Bacteroides thetaiotaomicron from the intestinal tract of a mouse, engineer it to add new functions, then re-introduce it to the rodents. By doing so, they moved one step closer to bioengineering bacteria for medical purposes.

This technique could also be used to detect long-term changes to the intestines that can result in inflammatory bowel disease or other conditions. Bacteroides, they said, could potentially express genes on demand, and since it already has stable interactions with human cells, it would likely be long-lasting designer bacteria.

Treating ‘major health-related problems’

Lu, senior author of the study and a biological and electrical engineer at MIT, explained that he and Voigt “took a lot of the tools that people are already using in other organisms” (like memory switches, ribosome-binding sequences, and CRISPR interference), “demonstrated that you could port all of these over into Bacteroides… [and] showed that genetic devices could be implemented in the bacteria and be shown to function in the context of the mouse gut microbiome.”

“The culmination of the work is not only do you have an engineered bacterium that’s colonized the mouse gut, but you can turn on which genes in the bacterium are active based on what you feed the mouse,” added Voigt. “That’s really something new. It allows you to control what the bacterium is doing at the site of where it’s operating.”

However, the researchers explain that there are still obstacles to overcome before their work can enter the human trial stage. For example, in order to colonize the mouse gut with the Bacteroides, the researchers first had to administer antibiotics to the rats. In addition, Lu and Voigt noted that they will have to demonstrate that the bacteria can be engineered with more complex behaviors and show that it can respond to multiple sensory inputs. Their ultimate goal is to engineer microbes capable of altering gene expression based on signals within the intestines.

“The big picture is that the bacteria that live in us or on us impact human health in very significant ways and the existing techniques we have to modulate the microbiome – taking antibiotics or changing our diet – are relatively limited. We’re hoping that with these tools to precisely engineer the intimate interface between bacteria and humans we’re going to be able to tackle some major health-related problems,” Lu said.


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