The gut has a lot to do with health. It’s not surprising, then, that scientists are increasingly probing the effects that microbes inhabiting it can have on wellness. Now, a research team at the University of Washington has created bacteria that can sense specific chemicals in the gut and help to keep us healthy.
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In the human gut are trillions of microbes that have a variety of effects on health. Evidence suggests that the composition of these microorganisms impacts not only physical health but also mental health.
It’s long been known that our feelings have a connection to our guts. How we feel can affect the gut, and the reverse is also correct. If there’s an imbalance in the amounts of chemicals produced by bacteria in the gastrointestinal tract, mental health issues can result.
Bacteria engineered in the lab of Dr. Tae Seok Moon at the McKelvey School of Engineering look to help with such imbalances. These will aid in detecting specific molecules in the gut that can be targeted to promote wellness.
The new research appeared in Cell Systems.
A major challenge
Before now, other scientists had attempted to use the same method that Moon’s team employed with minimal success. The technique involves developing a “bacterial sensor” to discern specific molecules in the body.
The main problem was specificity. In most cases, engineered sensors had difficulty differentiating between molecules that are similar in structure. This made them less useful.
“Specificity in engineering is one of the big challenges,” said Moon, an associate professor of Energy, Environmental, and Chemical Engineering. “But we have proved that this can be done.”
The genetically engineered bacterium Escherichia coli Nissle 1917 (EcN) offers proof. This microorganism detects only one specific molecule.
Building bacteria
It was not the first time that Moon would be working on sensors of this kind. He had previously developed similar sensors for oxygen levels, temperature, light, pH, pollutants, and molecules connected to diseases.
For the bacteria that detect specific molecules in the gut, the team began with a sensor pathway that exists naturally. It assessed how mutations would impact the sensitivity of this pathway, using computer modeling. The scientists then created a sensor pathway specifically sensitive to the chemicals they were interested in.
Next, the sensors developed were introduced into EcN, enabling them to distinguish between structurally similar phenylalanine and tyrosine. Phenylalanine is a factor in the rare birth disorder phenylketonuria (PKU), while tyrosine has a link to type 2 tyrosinemia.
Moon’s team also built sensors that can distinguish between phenylethylamine and tyramine, which are also structurally similar.
Applications and future work
Genetically engineered organisms, such as those in the current study, won’t only be useful in the medical field. Possible uses include controlling pathways for microbial metabolic engineering that are used for the production of some chemicals, pharmaceuticals, and fuels. Bacteria sensors may also be used to assess food quality.
However, these researchers are more interested in how the bacteria can be useful for boosting mental health and feelings of wellness. Moon has a special interest in using them to correct neurotransmitter imbalances. He has experienced this problem.
Some essential brain chemicals are synthesized by bacteria in the gut. For example, roughly 95 percent of the serotonin in the body is produced there. It becomes clear then what impact can be had on the brain when there is a problem in the gut.
Moon and his team members are looking to develop actuators. These are proteins that can help to correct disorders, working with information gathered by sensors.
References
Rottinghaus, A. G., Xi, C., Amrofell, M. B., Yi, H., & Moon, T. S. (2022). Engineering ligand-specific biosensors for aromatic amino acids and neurochemicals. Cell Systems, 13(3), 204–214.e4. https://doi.org/10.1016/j.cels.2021.10.006
