Nature

Bacterial “Computer Program” Can Heal Your Gut

October 30, 2015 | Sarah Tse

Bacteria microscopy
Photo credit: Bennett Lab, Rice University

Scientists have figured out how to genetically engineer different strains of bacteria so they can cooperate like different parts of a computer and have a powerful impact on your body.

We’ve already unlocked bacteria’s tremendous power to synthesize all kinds of useful products, like drugs, “designer” DNA, and biofuels. However, bacteria can have a much greater impact when different types work together. This powerful cooperative effect is seen in your own body where a vast network of microbes called your “microbiome” alters the way you metabolize food, fight off infections, and even think. So wouldn’t genetically-engineered bacteria also be more effective when they work together?

SEE ALSO: Altering Gut Microbes Could be Key to Curing Anorexia

In that spirit, a team from Rice University has devised a concept that harnesses the holistic power of multiple types of bacteria working in unison. They genetically engineered two different strains of E. coli bacteria, which are the most common bacteria in the human gut and play an important role in digestion and absorption of nutrients. These two distinct strains were altered to regulate gene expression in contradictory ways: one strain released signals that activated a set of genes, while the second strain created signals that repressed those genes.

When they combined the two strains, the signals released by each type of bacteria influenced the entire population, creating a regulatory system of positive and negative feedback loops. This meant that as the products of the targeted genes fell in concentration, the activating signals kicked those genes into high gear. When the products accumulated too much, the repressing signals stepped in to tone things down.

The coordination of the two strains resulted in an acutely responsive circuit that generated peaks and valleys, or oscillations, in the levels of gene products. The researchers tested the performance of each strain in isolation, and confirmed their findings: without its complementary partner, the bacteria could not reproduce those oscillating patterns of gene production.

This project has effectively created a bacterial system that mimics the complex communications between different organs and tissue types within a multicellular organism. For example, oscillations in certain signals and growth factors in an embryo determine almost everything about an animal, from distinguishing between the back and belly to dictating the minute growth of nerve endings.

These researchers have shown that genetically altering and combining bacteria can have the same comprehensive effect. Instead of fiddling with the existing and highly complex coordinations between cells in a multicellular organism, we can program and combine different strains of bacteria to work together and magnify a certain outcome.

Eventually, physicians might be able to design complex biological “computer programs” specific to each patient. Once ingested, the synthetic bacteria can communicate with the patient’s native gut microbes to correct their misbehavior. This technology could change the lives of people suffering from irritable bowel syndrome, type I diabetes, autoimmune disorders, and more.

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