Scientists engineer gut bacteria with built-in safety switch to tackle kidney stones

A team of researchers at Stanford University has developed a genetically engineered strain of ‘Phocaeicola vulgatus’ that may open new frontiers in microbiome-based therapeutics, particularly for preventing kidney stones.

The work, published in ‘Science’ and titled ‘Controlled colonization of the human gut with a genetically engineered microbial therapeutic’ demonstrates how the programming of gut microbes can both deliver targeted treatment and remain controllable within the human body.

The engineered microbe carries a five-gene pathway capable of degrading oxalate, a compound linked to kidney stone formation.

Moreover, to address concerns related to biosafety, the team built a survival mechanism. The microbe only survives when the host consume a certain prebiotic carbohydrate and disappears when the host stops consuming the carb.

In limited studies, the strain successfully reduced hyperoxaluria in mice, a known precursor to kidney stones. A phase 1/2a clinical trial extended these results to humans. It showed a dose-dependent presence of the bacteria, measurable decreases in urinary oxalate, and evidence of reversibility when trigger prebiotic was removed from the diet.

However, researchers acknowledged challenges with genetic stability. According to the study, horizontal gene transfer within the gut environment led to occasional “escape mutants” — bacteria that bypass the engineered safeguards.