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Genetically Engineered Bacteria Could Soon Be Monitoring, Treating Your Gut

by Conrad Scott | Herculean Strength
November 25th 2021, 8:47 am
Can we really predict how these organisms will behave?
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The role of the gut in physical and mental health is something we are now coming to appreciate more and more.

Research is revealing in greater depth that the gut really is a “second brain”, as some like to call it, with its own autonomous nervous system which must run properly if you want to be healthy and happy. And bacteria, far from being a threat to the proper working of the gut, are in fact essential to it.

Some of the trillions of bacteria living in your gut synthesize neurotransmitters that are responsible for your nerves, anxiety and euphoria. But when things go wrong and the gut flora become disturbed, for instance if a baby is born prematurely, things can take a serious turn.

Now researchers are proposing a novel high-tech solution to the problem of regulating the body’s “second brain”: genetically modified microbes that can not only detect imbalances within the gut, but also do something about them.

GM bacteria to regulate the gut

Tae Seok Moon, associate professor in the Department of Energy, Environmental & Chemical Engineering at the McKelvey School of Engineering at Washington University in St. Louis, claims to have experienced such imbalances himself.

“It is a difficult job to do,” Moon said, “to keep your neurotransmitters balanced.”

In 2017, Moon was awarded a grant to engineer a probiotic specifically aimed at protecting people from the negative health effects of adrenaline surges, and now his research has moved on to regulating the gut more generally.

His method involves the creation, through genetic engineering, of a “bacterial sensor” that can detect particular chemicals in the gut. The goal is a type of modular system which will feature a variety of different sensors. He has already developed sensors for temperature, pH, oxygen levels, light, pollutants and other disease-related chemicals.

Although Moon isn’t the first person to develop such sensors, until now they have suffered from lack of specificity, meaning that they have trouble differentiating between similarly structured molecules.

“Specificity in engineering is one of the big challenges,” Moon said. “But we have proved that this can be done.”

The proof is in the genetically engineered Escherichia coli Nissle 1917 (EcN) bacterium, which has a sensor for just one particular type of molecule.

The team was able to start with a sensor pathway found naturally in bacteria. Moon’s fellow researchers used computer modeling to explore how mutations would affect the pathway’s sensitivity. The researchers were able to develop a sensor pathway that was sensitive only to the molecules they were interested in.

The sensors were incorporated into EcN, allowing it to distinguish between phenylalanine (Phe) and tyrosine (Tyr), two structurally similar molecules associated with the disorders (PKU) and type 2 tyrosinemia.

Now that they have this proof of concept, Moon’s lab intend to work on developing an actuator, a protein that will act based on information gathered by the sensor.

In the case of PKU, for example, a genetic disease which causes babies to accumulate too much phenylalanine, a completely engineered bacteria might have a sensor to detect phenylalanine and an actuator that could then degrade it if the levels are too high.

This technology could also have uses beyond medicine. These engineered bacteria could also be used to monitor food quality or to regulate chemical pathways for the manufacture of many pharmaceuticals, fuels, or other chemicals.

Because of his experiences, however, Moon is personally most interested in bacteria that can sense the levels of neurotransmitters in the gut.

He says that he wants to put an end to the suffering people feel whose neurotransmitter levels are out of balance.

Of course, while many will be excited by the possibility of such an ingenious solution to the problem of gut dysbiosis, others will be disquieted by the use of genetically modified organisms.

As previously “science-fiction” technology moves off the screen and page and into the real world, the possibility of unforeseen consequences looms large.

Can we really predict how these organisms will behave?

Or will they surprise us, potentially in unpleasant ways?

Scientists have already discussed creating “killswitches” to turn off genetically modified organisms at will, for instance, if they begin to behave unpredictably or leave their specific environment.

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