Engineered E Coli from stool which can survive a hostile gut environment long enough to treat the disease

Now, a group of researchers from the University of California, San Diego, successfully engineered E. coli collected from both human and mice gut microbiomes and showed that they have the potential to treat diseases such as diabetes. Their finds are published in the journal Cell.

The team first collected stool samples from the host and extracted E. coli for further modifications. "We say to the bacteria: Hey, we will give you a new superpower, which you may not even benefit from, but we will put you right back into the environment that you thrive in," says Zarrinpar.

The superpower that the team gave to these specific bacteria is a protein called bile salt hydrolase (BSH). After a single treatment in mice, E. coli with BSH were found throughout the entire gut of the mice and they retained their BSH activity for the entire lifetime of the host. The group also show that the BSH activity was able to positively influence diabetes progression in mice.

This is a significant improvement over similar treatments with non-native laboratory strains of engineered bacteria, where more than one treatment is often required. And these engineered bacteria do not stay in the host's gut for nearly as long as, or as consistently as, the native E. coli method identified by Professor Zarrinpar's team.

In addition to successfully influencing diabetes in mice, the group was also able to make a similar modification to E. coli extracted from the human gut.

Ref:

Amir Zarrinpar et. al, Intestinal Transgene Delivery with Native E. coli Chassis Allows Persistent Physiological Changes, Cell, 4-Aug-2022, DOI: 10.1016/j.cell.2022.06.050