Scientists 'hack' common gut bacteria

MIT scientists have engineered a common bacteria in the human gut, with new functions, paving the way for designing microbes that could deliver drugs or detect long-term changes in the intestines.
One of the most common bacteria in the human gut, Bacteroides thetaiotaomicron, can now be engineered with new functions and re-introduced into the intestinal tract of a mouse, researchers said.
The work is a starting point for designing microbes that could eventually deliver drugs or detect long-term changes in the intestines that lead to inflammatory bowel disease or other illnesses, they said.
The Massachusetts Institute of Technology (MIT) group, led by synthetic biologists Timothy K Lu and Christopher Voigt, saw that Bacteroides had the potential to express genes on demand.

As a commensal bacteria, it has stable, long-term interactions with human cells and other microbes in the intestines. This means a designer bacteria and its offspring would be able to stick around for a while.
"We took a lot of the tools that people are already using in other organisms, (eg, promoters, ribosome-binding sequences, memory switches, CRISPR interference) and demonstrated that you could port all of these over into Bacteroides and get them working," said Lu, study senior author and a biological and electrical engineer at MIT.

"We then showed that genetic devices could be implemented in the bacteria and be shown to function in the context of the mouse gut microbiome," said Lu.

"The culmination of the work is not only do you have an engineered bacterium that's colonised the mouse gut, but you can turn on which genes in the bacterium are active based on what you feed the mouse," said Voigt, study senior author.
"That's really something new. It allows you to control what the bacterium is doing at the site of where it's operating," said Voigt.
A few challenges still need to be addressed before moving on to human studies. For instance, colonising the mouse gut with Bacteroides involved giving the animals antibiotics first.
Second, the researchers will need to prove that the bacteria can be engineered with more complex behaviours, such as being able to respond to many sensory inputs.

The eventual goal would be able to engineer microbes that can alter 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," Lu said.
The study appears in the journal Cell Systems.