Infant being tested for phenylketonuria

A newborn baby is tested for the genetic disorder phenylketonuria, which may be treatable with bacteria engineered to compensate for an enzyme that patients lack. Credit: Andrew Harrer/Bloomberg/Getty


Live bacteria deliver crucial enzymes straight to the gut

Intestinal microbes can be programmed to make up for a deficiency that causes a devastating inherited disorder.

Bacteria that live in the human gut have been engineered to churn out two key enzymes, providing a possible treatment for a serious genetic disease.

People born with phenylketonuria (PKU) cannot process the amino acid phenylalanine, which is found in most proteins. Even an extremely low-protein diet may not protect people with PKU from cognitive impairments caused by a build-up of phenylalanine.

A team led by Vincent Isabella at the therapeutics firm Synlogic in Cambridge, Massachusetts, inserted the genes for two enzymes that can break down phenylalanine into the Escherichia coli strain ‘Nissle’, a bacterium often taken as a probiotic. The engineered microbe slashed levels of phenylalanine in the blood of mice with a version of the disease. Healthy monkeys that were fed both protein and engineered bacteria experienced smaller spikes of phenylalanine in their blood than monkeys that ate only protein.

The results suggest that the bacterium might offer a way to prevent the toxic build-up of phenylalanine in people with PKU. A clinical trial is now evaluating the microbe’s safety in humans.