Engineered E. coli scavenges excess ammonia in the gut

Researchers continue to discover the key roles our gut bacteria can play in our health, but they can also engineer these microbes to diagnose and treat disease.

The biotech company Synlogic has been engineering bacteria to treat diseases associated with the gut microbiome for a decade. In Science Translational Medicine this week (2019, DOI: 10.1126/scitranslmed.aau7975), company researchers describe a strain of Escherichia coli that can reverse dangerously high levels of ammonia in the blood. “The data shows we can engineer bacteria to carry out a specific function, deliver them to humans and that they perform as designed,” says Paul Miller, Synlogic’s chief scientific officer.

Our bodies mostly produce ammonia while metabolizing protein in the intestines, and the liver then turns it into urea. Liver diseases and some genetic disorders can disrupt this process and cause ammonia to build up in the blood with severe consequences due to ammonia’s toxicity. Current treatments for these conditions either try to reduce the activity of ammonia-producing bacteria in the gut or physically adsorb the ammonia once it is made.

In the new approach, the Synlogic team modified E. coli Nissle 1917, which is sold as a probiotic under the name Mutaflor in Europe. The engineered bacteria, which is called SYNB1020 and can be taken as a pill, metabolize ammonia in our guts, turning it into the amino acid l-arginine. Tests showed that the engineered bug reduced ammonia levels and increased survival in mice with excess ammonia in their blood. In a Phase I clinical trial in healthy people, SYNB1020 survived the passage through the digestive system but didn’t colonize the guts long term, another feature the researchers engineered into the bacteria.

“It’s good to see real world applications coming into practice,” says Pamela Silver, who works on gut microbiome engineering at Harvard University. “We are good at engineering bacteria and are getting better all the time. This is a rapidly growing area and the more successes the better.”

SYNB1020 is now in Phase Ib/IIa clinical trials.