Designer Microbes Might Be Coming To A Gut Near You

Bacteroides thetaiotaomicron (white) living on mammalian cells in the gut (large pink cells coated in microvilli). Janet Iwasa/MIT.

The bacteria living inside your body outnumber your own cells 10 to 1. With such an abundant population of microbial guests in our bodies, why not start ordering them to do some housework? Biologists from MIT have successfully taken bacteria found in the human gut and genetically modified them to have useful properties, such as monitoring intestinal health and alerting us when there's something wrong.

This isn't the first time that microbes have been genetically engineered to have new properties: E. coli has been genetically altered in the past, however this microbe is present in relatively small amounts in the gut.

More recently, biologists from MIT looked at a common gut bacterium that is more abundant: Bacteroides thetaiotaomicron. They succesfully developed a genetic 'toolkit' to switch on and off different genes in the bacterium, and re-engineered the microbes so that they would perform new functions when reintroduced into the gut of a mouse.

“Using these parts, we built four sensors that can be encoded in the bacterium’s DNA that respond to a signal to switch genes on and off inside B. thetaiotaomicron,” Christopher Voigt, an MIT biological engineer and study senior author, says. Details about this incredible toolkit can be found in Cell Systems.

This species of bacteria has properties that are favorable for long-term treatments: For one, it's stable in the gut and thus won't get wiped out by the immune system immediately. These organisms also interact with our cells and other microbial inhabitants for prolonged periods of time, so they have a long shelf life of activity. And there's also a lot of them to work with.

The bacteria can be engineered to sense and report particular conditions in the gut, such as bleeding or inflammation. When the bacteria pick up these problems, they react in detectable ways such as glowing.

This new designer bacterium also has the potential to be controlled based on what you eat as some of the signals they detect can be food ingredients, like sugar. "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," adds Voigt. "That's really something new. It allows you to control what the bacterium is doing at the site of where it's operating." This might mean exercising self-control when deciding what food to eat after receiving a bacterial treatment to get the best results.

This treatment has yet to make the transition from mice guts to human guts. There are still some challenges that need to be addressed before this can happen. Recolonizing the gut with designer bacteria involves wiping out the previous bacterial population with antibiotics first so that the new bacteria have a chance to establish themselves and grow. A process that is not risk-free.

"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," said Timothy Lu, the other senior author. "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."

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