Antibiotics have long been the go-to treatment for a bacterial stomach bug. The fact that they eliminate harmful bacteria while also disrupting the broader gut microbiome is accepted as a necessary side effect. University of Rhode Island researcher Amanda Alker intends to disprove this by developing targeted microbiome-editing approaches using CRISPR-associated transposons, or CASTs, to precisely alter disease-causing bacteria without harming beneficial microbes. The research also explores environmental applications, including aquaculture, where harmful vibrio bacteria in oysters could be neutralized without antibiotics. By enabling targeted interventions, this emerging field could reduce antibiotic use and offer new strategies to control disease.
What is the biggest hurdle your team needs to overcome before microbiome editing can move from proof of concept to real-world use? Microbiome editing faces several hurdles. We need to identify bacterial targets – which bacteria and genes to disrupt – and adapt editing tools to work consistently without off-target effects, requiring adequate DNA sequencing data to pinpoint unique guide sequences. Delivery strategies must also be optimized to get editors into hosts efficiently. Key unanswered questions remain: What are the ecological consequences of shifting microbiome composition, and how stable and controllable are the edits? Long-term effects on community health are largely unstudied. Finally, biosafety measures must ensure that DNA editing is used ethically and that risks are mitigated.
Which diseases or conditions do you see as the most realistic first applications for this technology? This technology is best suited for diseases with a known pathogen whose virulence genes directly cause the condition. Food-borne illness is a strong first candidate: a University of California Berkeley colleague recently demonstrated that microbiome editing could inactivate virulence genes in enteropathogenic E. coli, responsible for over 300,000 deaths yearly. For human applications, a local or topical setting (oral or skin microbiome) is ideal since delivery tools would be more accessible. Ethically, these interventions are best motivated where antibiotic treatments are limited or not an option.
How does your oyster research translate to potential human health treatments? Developing microbiome editing for oysters relates to human health treatments in two parts:
1. The consumption of raw oysters is associated with an increased risk of gastroenteritis from a group of bacteria called vibrio that can cause food-borne illness in humans. These bacteria exist naturally in aquatic environments and thrive in the summer.
2. The most promising class of microbiome-editing tools was first discovered occurring naturally in vibrio, making them a perfect model system to address some of the major outstanding questions about the ecological consequences of microbiome editing. By working with vibrio, we can see how the editors behave naturally, which will clarify the biosafety implications for translating these technologies as human interventions for bacterial illnesses.
What timeline do you envision for this work to begin influencing clinical or commercial practices? Commercial adoption of microbiome editing (e.g., agriculture) might occur faster than clinical practices given the differences in regulatory oversight. There are many scenarios where bacteria are grown in controlled environments (such as bioproduction and fermentation), where the technology could be adopted relatively quickly without the same concerns as a therapeutic for humans. I envision proof-of-concept advancements across various systems to occur over the next five years, followed by another five years of clinical feasibility investigation.
