The human gut microbiome has been shown to impact health in a myriad of ways. The type and abundance of different bacteria can impact everything from the immune system to the nervous system. Now, researchers at Stanford University are taking advantage of the microbiome’s potential for fighting disease by genetically modifying certain bacteria to reduce a substance that causes kidney stones. If scientists are successful at modifying gut bacteria, this can lead to therapeutic treatments for a wide range of diseases.

However, the study, published in Science, shows that this is not a simple task. The researchers used the bacterium Phocaeicola vulgatus, which is already found in the microbiome of humans, and modified it to break down oxalate and also to consume porphyran, a nutrient derived from seaweed. The porphyran was used as a way to control the population of Phocaeicola vulgatus by either adding more porphyran or reducing the amount, which should kill off the bacteria due to a lack of food.

The study was made up of three parts: one testing the modified bacteria on rats, one trial with healthy humans and one trial on people with enteric hyperoxaluria (EH). EH is a condition in which the body absorbs too much oxalate from food, leading to kidney stones and other kidney issues, if not treated.

In the first part of the study, rats with increased oxalates in their diet experienced a reduction in urine oxalate by up to 47% when the modified bacteria were added to their microbiome. Then, the researchers induced EH in rats through a certain gastric bypass procedure that is known to result in EH complications in humans. The results were promising.

The study authors say, “Surgery resulted in a 51% increase in the urine oxalate in rats colonized by the control strain, an increase that was completely eliminated in animals harboring the oxalate-degrading strain.” Furthermore, the modified bacteria were successfully eliminated when porphyran was no longer given to the rats.

The researchers then tested the modified bacteria in 39 healthy humans in a phase 1/2a clinical trial. The results indicated that colonization in humans was dose-dependent—meaning as they increased the porphyran, the Phocaeicola vulgatus population increased—and was reversible upon porphyran removal in most cases. However, two participants showed the persistence of Phocaeicola vulgatus in their microbiome, even after an antibiotic treatment.

This indicated that the bacteria had mutated by swapping genetic material with other bacteria in the microbiome. Luckily, the participants did not experience any dangerous effects from the prolonged colonization. Still, this mutation highlights kinks that remain in the process.

The results for EH patients also showed that they experienced issues, but still showed some progress. Six out of nine participants with EH underwent treatment, and on average, these participants experienced a 27% reduction of oxalates in their urine. This result is not considered statistically significant, but it does offer some hope for future studies with a larger sample size.

The EH group also showed evidence that some degree of genetic mutation occurred in the modified bacteria. Over time, the efficacy of the modified Phocaeicola vulgatus was degraded due to gene transfer with the surrounding bacterial strains. This did not cause adverse effects in the participants.

This study affirms that some challenges remain, but that progress is being made. Future research can help to refine methods and reduce the chance of mutations in modified bacteria. The authors are overall optimistic, stating, “We showed that it is possible to colonize humans with an engineered gut commensal for a sustained period at high levels. A single dose of the strain was sufficient for colonization if the subject was provided proper gastric protection, and even at high doses of porphyran, the treatment was safe and well tolerated.”

© 2025 Science X Network