Part 1: The Case for Genetically Engineered Probiotics
Engineered probiotics address several critical shortcomings of the current industry. For example, many existing products lack differentiation and fail to provide targeted and consistent benefits to the consumer. Currently, some variation on a composition of Bifidobacterium, Lactobacillus, Saccharomyces, Enterococcus, Bacillus, etc. is found in nearly every product, where the main differentiator is often the advertised colony forming units (CFU) per dose, despite lack of scientific evidence that “more is better” for that particular population. In contrast, genetically engineered microorganisms (GEMs) can be tailored to a specific use-case more simply and safely than hunting down novel isolates with the desired function, and a single strain can be optimized to provide a benefit at much lower CFUs.
To expand the current repertoire of probiotics, companies have resorted to scouring nature in an attempt to find strains with uniquely beneficial properties. This approach requires a large investment of time and money to not only identify said strain, but also prove its efficacy, safety, and feasibility as a consumer product. Once discovered, the strain is not patentable and will eventually be added to the list of off-the-shelf products. With a much quicker turnaround time, we have the option to build strains with the benefits we desire while not limiting ourselves to, for example, bacterial pathways found in pre-established probiotics, or enzymes that are stable enough to be purified and delivered orally. We can expand the use-case of probiotics and rapidly respond to significant global challenges, such as emerging health threats and extreme climate change. We envision a future with GEMs that can mitigate our exposure to microplastics, highly processed foods, and air pollution, which are increasingly prevalent in our environment and new to our biology.
The development of GEMs to tackle unique challenges, and the speed with which we can develop new strains for testing, highlights not only the immense potential of genetic engineering but also an opportunity to reduce costs and make products with genuine functions more accessible. The technology to build and test GEMs has evolved immensely, streamlining the process of getting the next generation of probiotics into the hands of the everyday user. And while many companies fear consumer rejection of GMOs, the market for genetically engineered probiotics is growing. Contrary to widespread belief, most people (in the US at least) are not specifically opposed to all GMOs outright, and they are more than happy to purchase products that provide them with the benefits they want, provided there is transparency and clear communication about their safety and efficacy. By being open about the genetic modifications, educating the populus on how the technology works, and clearly describing the benefits they offer, companies can foster consumer trust and acceptance. This approach not only builds confidence in the technology but also encourages informed decision-making among consumers, and there are now companies who have demonstrated success in the consumer space with transparently labeled GMO probiotics. When companies transparently and responsibly use genetic engineering to develop new products with targeted benefits for the end user, people will appreciate the improvement and make the conscious decision about which GEMs they want to include in their daily lives.
Part 2: The Case for Regulation and Industry Standards of Genetically Engineered Probiotics
The emerging field of genetically engineered probiotics necessitates robust safety considerations and meaningful regulations to ensure its success. Safety is paramount, as it not only protects consumers but also paves the way for the industry’s growth and acceptance. Innovators in the biotechnology space generally want to do the right thing, and by having accessible and clear guidelines, we can make it easier for future companies to contribute to the success of the industry. As scientists who are encouraging the use of GEMs, we want to ensure that there aren’t well intentioned but ill-informed innovators releasing potentially hazardous products that could lead to reactionary regulations and stifle innovation.
We, along with other academics, industry representatives, and regulatory officials, believe a voluntary framework for regulation is an essential first step towards properly regulating genetically engineered probiotics. Such a framework would allow the industry to establish best practices and standards, providing a playbook for safe and effective development. This approach also encourages transparency and accountability, building trust within the community and creating space for continued innovation. As we set new standards, we can iterate on the framework as the technology grows, such that inevitable government regulations reflect the learnings of scientists in both industry and academia.
We envision, as part of the voluntary framework, tools to provide guidance to those who want to use GEMs in product development. Akin to decision trees for the history of safe use in the food ingredient space, we believe a safety assessment during the design phase can reduce risks by limiting the potential unknowns of a GEM. And at least in the nascent stages of this category, we advocate for a conservative and risk-minimizing approach. For example, if a probiotic is intended for release, a series of questions can help to calculate the likelihood of causing ecological disruption, the potential to break evolutionary bottlenecks, and the risk of introducing untested functions into an ecosystem. We are currently working with the American Society for Testing Materials (ASTM) on that exact guideline (WK84273). And as we develop this, we have been and continue to solicit feedback and input from experts in academia, government, and industry to reflect the current state of the field as much as possible. Collaborative efforts are going to be instrumental in setting these standards.
We fundamentally believe that regulation should focus on assessing each GEM product individually. For example, GEMs that are constructed of sequences reasonably likely to have previously existed in nature in the intended ecosystem result in final products with lower risk. Additionally, final strains should adhere to traditional safety considerations including being stable to mutation and free from risky components, such as transposable elements, antibiotic resistance, and pathogenicity. These, among other careful approaches to genetic engineering, ensure that the resulting probiotics are both effective and safe for long-term use. These evaluations are best made at the design stage to streamline safe product development and limit large resource investments into potentially hazardous GEMs.
Conclusion
Genetically engineered probiotics hold immense potential to improve our lives and through this create a burgeoning industry offering tailored solutions to modern health and environmental challenges. However, this potential can only be realized through a commitment to safety, transparency, and scientifically motivated regulation. By building trust with the community and establishing clear standards, we can create a sustainable future for genetically engineered probiotics, benefiting both the consumer and the biotech industry.
