Walk into any grocery store, and it won’t take you long to find the “gut-health” section: racks of yogurts and kefirs and dozens of small glass bottles of probiotic “shots” touting billions more “active cultures” than their competitors sitting next to them.With the recognition of the microbiome as a major player in human health, the number of companies marketing probiotics has skyrocketed. It can be difficult for consumers to wade through the myriad options available, particularly when most health claims are vague and the likelihood that the probiotic that worked for your cousin’s friend’s brother-in-law is going to work for you is slim at best. In such a saturated market, it will take a company dedicated to good, sound science to fully unlock the potential of the human microbiome and bring consumers products that actually work.One company is well on its way toward fitting that bill. Working quietly behind the scenes for more than two decades, it has built a world-class microbiome research and product development facility. Now supplying a third of the world’s probiotics, this company is poised to transform our approach to health nutrition.Chances are, you already know this company.This company is DuPont.So, how did a 200 year old company known as a leading producer of materials like polymers, chemicals, and textiles also become the world’s leading producer of probiotics?It all started with animal nutrition and dairy cultures.
For decades, a Danish company called Danisco built world class capabilities in animal nutrition, dairy cultures, and probiotics for human use. A series of targeted acquisitions (Cultor in 1999, Rhodia Foods in 2004, and Genecor in 2005) significantly boosted the company’s overall capabilities in health and nutrition and microbial science and technology -- including how to improve gut health in farm animals to limit the use of antibiotics and improve nutrient absorption, identify better microbes/starters for the dairy industry, and develop and market probiotics to improve human gut health.Part of the success of the company in these areas was due to the suite of experimental tools for studying gut science that Danisco had been developing as early as the 1990s. “We called this our ‘Enteromix® toolbox’ – and we still do!,” explains Andrew Morgan, DuPont Fellow and former Chief Scientist. “This has been added to over the years to create a world leading health and nutrition science platform.”The platform includes one of the first laboratory-based gastrointestinal simulators used initially to mimic the chicken gut and adapted to model the human gastrointestinal tract. “One of the first uses of the company’s nascent Enteromix® toolbox was to demonstrate that one of the mechanisms of action of its pioneering animal nutrition enzymes was modulation of the gut microbiota. This was the beginning of our journey into the microbiome,” says Morgan.In 2011, DuPont acquired Danisco, which by then was an established leader in the human probiotics market and had also developed and marketed some direct-fed microbials (probiotics for livestock). Though the benefits of live microbes were clear, the rationale for such efficacy and the breadth of potential applications was not yet fully understood. In 2012, microbiologist John Gannon, who was part of DuPont’s Central Research and Development, had been trying to convince DuPont to start paying attention to microbiome opportunities beyond human probiotics.
In 2014, DuPont’s Biologicals Venture accepted Gannon’s proposal to explore the microbiome of crops to search for crop probiotics -- called biologicals. They began working on corn and observed that some plots in the same corn fields had much higher yields than other plots, with no difference in corn genetics, soil conditions, or other growth conditions. The hypothesis was that the differences may have been due to the microbiome.
Image source: John Gannon/DuPontGannon and his team discovered that the differences in yields were due to bacteria found in biofilms on the roots of the plants. DuPont’s microbiome efforts quickly gathered steam, and soon, the company also initiated a deep exploration of the microbiomes of livestock, such as poultry, to find new direct-fed microbials to mitigate diseases. All of this became the foundation for a world class microbiome research and product development capability not only for agriculture and livestock, but also for human health.After coming into the DuPont Industrial Biosciences business, Gannon was tasked with building the Microbiome Research Competency. “The idea was to bring together genomics, bioinformatics, microbiology, molecular biology, fermentation, and data analytics to enable a systems biology approach, and then to use that to deliver microbiome based-benefits.to the myriad of microbiome-based opportunities,” he says. It is that approach that makes DuPont stand out in a field rife with hype, skepticism, and unfounded promises.
Building on what they learned in the corn fields, DuPont developed a streamlined, universal pipeline for identifying and developing probiotic candidates. “No corners are cut in the process, ensuring the science the company does is sound and a top priority,” says Gannon.
Image source: John Gannon/DuPontIt all starts with a pilot study to determine the most appropriate sample or set of samples for the target or concern that is being addressed -- whether that be a pathogen affecting a flock of chickens or a metabolic disease in humans. Two of the most critical pieces to a successful microbiome study, says Gannon, are the sample collection process and the metadata.“Sample collection is critical -- we tell people to treat it like a crime scene to avoid cross contamination, and we work with people that intimately know the target -- veterinarians for livestock, farmers for agriculture, clinicians for human disease,” says Gannon. “You also have to understand your metadata,” he adds. “It’s an important part of putting the science behind it, and many people don’t think about it enough.”Once the appropriate sample type is identified and samples are collected, DNA is extracted to obtain a microbial profile of the sample. Using a suite of bioinformatics tools, the team figures out which microbes appear or disappear under certain conditions (low crop yield or sick livestock, for example). These microbes are then grown in the lab and put through a series of screening assays to determine whether they are good probiotic candidates or not. Growth conditions of the candidate organisms are optimized to maximize yields and optimal conditions for stability and delivery are established. Only then is a probiotic candidate ready for trials to see how it performs in the real world -- which, just as the sample collection component, is conducted in partnership with veterinarians, farmers, or clinicians.
Importantly, says Gannon, interactions between different bacterial species are a critical consideration because in real-life, these microbes are not isolated -- they are members of a microbial community of different species with different functions. It is this emphasis on community function, not just structure, that is at the core of DuPont’s workflow, says the company’s Human Microbiome Venture Leader, Sebastien Guery. This helps the company maximize the chances that their probiotic will thrive in its intended environment so it can elicit its beneficial effects.To this end, DuPont places a lot of emphasis on understanding the mechanism of action of a given strain as well as identifying relevant functional pathways. Doing so allows DuPont to focus on restoring the missing functions or fueling the relevant functional pathways within a given microbial ecosystem to maximize efficacy. Critically, they aim to develop not only new microbes but also molecules like prebiotics or postbiotics that only help ”friendly” microbial species (helping the “enemy” bacterial species also grow defeats the purpose, after all). This approach is used successfully in human and animal health to develop superior ingredients modulating the microbiota, and is how DuPont applies today’s Enteromix® health and nutrition science platform to screen in vitro models before moving to clinicals.“With the right enzymes and the right feed raw materials, we can generate prebiotics in situ -- within the gastrointestinal tract of a farm animal. These prebiotics are designed as a selective food source to promote the growth of the good bacteria in the gut. It’s what we discovered all those years ago and have been building on ever since. It’s a bit like personalized nutrition for microbes,” says Morgan.
Guery sees personalized nutrition in the future for improving and restoring human health as well. By not only understanding the functional potential of the microbes themselves, but also linking that to the affected functional pathway(s) in the host, the door to personalized interventions is opened, he says.“We’re moving from one-size-fits-all diet and supplementation to tailoring supplementation and diet to the needs of the patient to maximize success. This opens a new field called ‘Nutrapeutics’ -- the use of nutrition and supplementation as therapeutic adjuvants to maximize efficacy of administered medicines”In the short term, the company is focusing on metabolic conditions -- but long-term goals include immuno-oncology and gut-brain axis related diseases, among others. When it comes to what we are learning about the microbiome, the possibilities are endless and there is still a lot that we don’t understand, so the ultimate vision, says Guery, is “to transform health, nutrition and wellness using a tailored mix of microbes, prebiotics, enzymes, and proteins to restore microbiota composition and function.”The recent organizational change that led to the creation of Nutrition & Biosciences is a critical step toward propelling DuPont to achieve that vision.
“What we have now is a fantastic discovery machine that can not only focus on discovery of prebiotics and probiotics, but also engineering microbes, proteins and enzymes,” Guery says of the new division. “[It is] the perfect engine to look at microbiome modulation, because not only can [we] seed a missing microbe, but we can restore very selectively a missing microbiota function.”Whether or not the company will start leveraging engineered probiotics tailored for specific functions remains to be seen, though Gannon says it’s something they’ve talked about. Right now, though, Gannon and Guery agree that the bigger focus is overcoming the snake oil that’s out there and restoring consumers’ faith in probiotics.“We have to fight against all the hype, there’s a lot of bad product out there,” says Gannon. “There are [companies] that have a bug and they put it into some kind of product and say, ‘hey, probiotics, they’re going to solve all of your problems,’ and it’s not true. Good marketing does not always match up with good science and when that happens credibility is lost. Putting strong science behind the microbiome research is a game changer that will strongly benefit humans, animals, crop yields, and the environment. We are in the early days of the microbiome age, so this is a very exciting time to be a microbiologist,” he says.Gannon himself was a big skeptic of probiotics not that long ago, but being immersed in DuPont’s microbiome research and validating in vitro results with in vivo trials has made him a firm believer. Nevertheless, he is among the first who will tell you that microbial-based therapeutics aren’t the silver bullet; they can’t treat or cure everything. But with companies like DuPont having paved the way all those years ago and still leading the way with responsible science, microbes are likely to have an important place in the future health of our lands, our animals, and our own selves.Meet DuPont at SynBioBeta 2019 this October 1-3 in San Francisco, CA. Vince Sewalt, Global Lead of Regulatory Science & Advocacy at DuPont Nutrition & Biosciences, will be joining the “What’s your biostrategy? Chemicals and Materials” session at 5:45pm on Wednesday, October 2.