A new Evans School study led by Weston Whitaker has brought to light exciting breakthroughs in this field. This study uniquely addresses the issue of genetically modified gut microbes. Pioneering work appearing in the journal Science has addressed health concerns related to oxalate absorption. The resulting increase in absorption can predispose individuals to the development of kidney stones. This was a combined pre-clinical study in animal models and nearly completed human trials, currently including a racially diverse group of participants.
The real innovation is the engineering of gut bacteria. Today, they are able to efficiently break down both oxalate as well as porphyran, a polysaccharide typically found in seaweed. The vast majority of humans and their gut bacteria are incapable of digesting porphyran. The researchers wanted to support their gut ecosystem, so they provided the modified bacteria a consistent source of fuel by adding porphyran to the diet. This strategy aims to decrease a person’s risk of developing kidney stones.
Study Design and Methodology
Primary species used in the study for mechanistic testing as well as in vitro tissue extrapolation to human. Two distinct human trials were conducted: one with 39 healthy volunteers and another with 20 individuals diagnosed with enteric hyperoxaluria. This life-threatening condition is most simply described as too much oxalate being absorbed, which leads to the repeated formation of kidney stones.
It was necessary that the modified bacteria were stably established in the participants’ gut flora. The results varied significantly among individuals. In two of the participating humans, the genetically modified microbe was fully cleared from their systems. In sharp contrast, in two of the other participants the bacteria were able to live on in their guts. Interestingly, in these healthy participants, these bacteria changed and started to metabolize other things than porphyran during the study.
Dr. Whitaker commented on the mixed outcomes of the study, stating, “Many aspects of the technology worked surprisingly well, and we’ve clearly identified parts needing further development.”
Findings and Implications
It is clear that the results from this research illustrate exciting potential opportunities, but starkly highlight significant risks related to genetically engineered bacteria. As a result, the research team felt that the trial could not continue. What was happening, the researchers found, was that these engineered bacteria were vanishing from participants immediately after they stopped consuming porphyran. Even with these disappointments, the team of researchers is still hopeful about the development of this technology.
Dr. Forster emphasized the potential benefits while acknowledging the inherent risks. “There are risks associated with these approaches but it’s an amazingly powerful technology and these types of studies provide a key fundamental understanding.” He further stated that knowing how bacteria swap DNA is key not only to using this process therapeutically but to ensuring it is safe.
Dr. Whitaker expressed hope for future applications, saying, “I think we showed that there is promise in continuing this approach.” He noted that some of the genes and activities introduced are commonly found in healthy guts, making them a relatively safe initial application.
Future Directions
The results of this study may pave the way for future research into using genetically modified microbes for various therapeutic purposes. Many specialists think we haven’t made the best use of natural species as therapies. Others maintain that the path to the most cost-effective solutions comes through genetic modification.
Dr. Forster remarked on the importance of continuing research in this area: “This paper is a key step in that process.” He pointed out that while some naturally occurring species may offer advantages, “in some cases… genetically modifying them provides a much more efficient way of providing that therapy.”
