Engineering Gut Bacteria to Fight Kidney Stones: Promising Results from Clinical Trials

The human gut microbiome significantly influences health across various systems. The diversity and abundance of bacteria can affect aspects ranging from immunity to neurological functions. Now, Stanford University researchers are exploring the microbiome's potential in combating diseases by genetically modifying specific bacteria to reduce substances that cause kidney stones. Successful modification could lead to new therapeutic approaches for numerous conditions. However, as detailed in a study published in *Science*, this task is complex. Researchers modified Phocaeicola vulgatus, a bacterium already present in the human microbiome, to break down oxalate and consume porphyran, a seaweed-derived nutrient. The amount of porphyran controlled the population of Phocaeicola vulgatus—when increased, it supported bacterial growth; when decreased, it led to their elimination due to starvation. The study comprised three phases: testing on rats, trials in healthy humans, and trials with patients suffering from enteric hyperoxaluria (EH). EH is a condition where the body absorbs excess oxalate from food, leading to kidney stones and other complications if untreated. In the rat phase of the study, animals fed diets high in oxalates showed up to a 47% reduction in urine oxalates when administered the modified bacteria. The rats then underwent surgery known to induce EH, replicating human conditions. "Surgery caused a 51% increase in urine oxalate in control rats, but this effect was entirely reversed in those with the oxalate-degrading strain," noted the authors. Additionally, upon ceasing porphyran administration, the modified bacteria were eliminated safely in these rats. The researchers then conducted a phase 1/2a clinical trial on 39 healthy human participants, revealing that colonization by Phocaeicola vulgatus was dose-dependent and reversible with porphyran removal. However, two individuals continued to harbor the bacteria even after antibiotic treatment, due to genetic material exchange with other gut microorganisms. Fortunately, these mutations had no adverse effects on the participants. For EH patients, the results were mixed but promising. Of nine participants treated, six showed an average 27% reduction in urine oxalates, a statistically modest yet encouraging outcome suggesting potential benefits for further research. Genetic mutations were also observed but did not cause any harmful effects. The study acknowledges lingering challenges but remains hopeful. Future work may refine these methods and reduce the risk of genetic mutation. The authors optimistically concluded: "We demonstrated that humans can be colonized by an engineered commensal gut bacterium at high levels over a sustained period. A single dose sufficed for colonization if adequate gastric protection was provided, and even high porphyran doses proved safe." Written by our author Krystal Kasal, edited by Gaby Clark, and fact-checked/reviewed by Andrew Zinin—this article is the product of meticulous human effort. We depend on readers like you to sustain independent science journalism. If this reporting matters to you, please consider a donation (especially monthly). You'll receive an **ad-free** account as our thank-you gift.