Probiotics, a field that seeks to use edible bacteria to improve human health, may soon undergo a metamorphosis. Students at MIT and Caltech are using the techniques of synthetic biology to create bacteria that fight cavities, produce vitamins, and treat lactose intolerance, as part of the International Genetically Engineered Machines (iGEM) competition at MIT. The new research might lead to a cheaper way to produce medicines or improve diets in the developing world.

Synthetic biology is the quest to design and build novel organisms that perform useful functions. Much research in the field has concentrated on using bacteria as a factory. But the new projects are attempts to enhance the health benefits of edible bacteria.

These projects capitalize on the fact that our bodies are already colonized by billions of bacteria. Our mouths, for example, are a haven to bacteria, both good and bad. Bacteria that live in the dental plaque, called Streptococcus mutans, feed off of sugar on our teeth and then excrete acids, which wear away dental enamel and cause cavities. To create cavity-fighting microbes, the MIT team started with a peptide—a short protein segment—that has been previously shown to prevent the bad bacteria from sticking to the teeth. The team built a piece of DNA containing both the gene that makes the peptide and a gene for a molecular signal that causes the bacterium to excrete it.

The next step will be to insert this piece of DNA into Lactobacillus bulgaricus, a microbe common in yogurt. The students haven’t done that yet, but they have successfully introduced foreign DNA into the microbe, which primes the microbe for further genetic engineering.

If the microbe can be successfully engineered, eating yogurt would deposit it on the teeth, where it would produce the protective peptide.

One central project in synthetic biology is the attempt to create a huge, publicly accessible “parts list,” a catalogue of gene sequences and the functions of the resulting proteins. The MIT team doesn’t intend to develop a product for commercial use, but the biological parts that it creates might one day be used in other applications.

The Caltech team focused on microbes in the gut, aiming to create a microbial solution to lactose intolerance.

Lactase pills are available to help people digest milk products, but the Caltech students wanted a more permanent solution. They started with a strain of E. coli often used as a probiotic in Germany. The strain, called Nissle 1917, was originally extracted from soldiers in World War I who were immune to an extreme gastrointestinal virus that swept through an army camp.

The students added three biological parts to the Nissle bacterium: a gene that produces the lactase enzyme, a receptor that recognizes lactose, and a sensor that causes the cell to break open at a certain concentration of lactose. With this system, bacteria in the gut would constantly produce lactase. When the receptors on a bacterium’s outer surface bound to a sufficient amount of lactose, they would trigger the explosion of the cell, releasing lactase into the intestine to break down the sugar. The students have so far created the first two components but are having trouble designing the microbes to self-destruct in the proper manner. The team is also working on an edible microbe that would produce folate, a vitamin important for preventing birth defects.

—Emily Singer, Technology Review, 11/11/08