Persephone puts poop to work to study and heal your gut microbiome TechCrunch


What’s going on in your gastrointestinal tract? Well, we have a general idea, but evidence is mounting that the gut and the microbes that live there play an important role in many health problems. Persephone is a biotech startup that – with the help of 15 million dollars and a a lot feces – builds a library of the human microbiome and collects the best list of beneficial life forms that can do everything from ease digestion to fight serious disease.

The democratization of once exclusive and expensive tools like rapid genetic sequencing has fueled a new generation of biotech companies and therapeutic approaches. In this case, it’s looking more closely at how everyone’s microbiome—the often unique array of microorganisms that live in and on our bodies and perform different tasks for mutual benefit—and what those differences mean for our health.

Co-founder Stephanie Kaller comes from a genetics background at Genomatica, where they worked on producing chemicals typically derived from oil by modifying bacteria to ferment it.

“It took 5 years of genetic engineering, but it worked. it allowed us to create a project to engineer bacteria,” he said. “Now we’re doing something similar using the same tools. But we used to map a single microbe, but now we’re doing it across multiple microbes, building a precise map of the entire gut biome.”

He explained that there is a fundamental lack of understanding in this area. Despite evidence that it is involved in many processes, historically there has not been enough data to answer questions like how the microbiome affects things like disease progression, therapeutic efficacy, immune system development, even allergies. The reason why is the difficulty of collecting enough research material.

Persephone’s all-in-one dirt collection.

The company trained machine learning models on large data sets that it collected itself through a laborious collection of stool samples from both healthy people and people with various conditions.

“It is not easy to give stool samples. there’s a stigma,” Culler explained. “So we focused on how to do it easily. We received our initial funding through Y Combinator [one of our favorites in 2018] created us to develop that infrastructure, to get large volumes of patient data.”

The microbes in the samples were isolated, sequenced, and cataloged, and then the data was combined with a host of other health records—blood tests, behavior, medications, and more. Machine learning is an effective way to sort through such noisy data, and it identified both examples worthy of study and what Culler called “superheroes” in microbes.

For example, a particular strain or functional type of bacteria may die in the gut in the years before a colorectal cancer diagnosis. Why? No one knows, but you don’t have to know that such an early marker to save lives. What if his presence could be restored? It may very well have a positive therapeutic or preventive effect.

“You and I may have different strains of the same bacteria, but there’s a set of good functions that you want,” Kahler said. “But then in disease studies, they can be completely absent, or they have other, scarier strains.”

Researchers work in a lab in the Persephone Biome.

Image credits: Persephone Biome:

“As we get older, our diet changes, we get sick, we take antibiotics … and the microbiome starts to disappear,” he continued. “We try to collect all the right microbes. one size fits all, built on our data, a consensus of organisms that all need; one super pill that is a new category of probiotics.”

It’s a little more complicated than that, however, Culler elaborated. Different age ranges and conditions are likely to have different needs, although a superhero collection is likely to be useful (and certainly not harmful) to anyone.

You may be wondering how they differ from the probiotic pills and drinks that already exist. Well, they may be beneficial to some, but the truth is that they are not really our local microfauna.

“Most of what we have on the market are heritage strains that were discovered over 100 years ago, many of which are from milk-based products; they are not true members of the gut microbiome. We analyzed 150 products and there were only 29 strains that matched a healthy microbiome,” Kaller said. (And no superheroes).

Compare that to the thousands of candidates they’ve discovered, all of which have come directly from humans, and more recently, so they reflect, among other things, the modern diet. Instead of animals found in milk a century ago, you can have the best breed from real people.

There are two broad paths for Persephone, both of which the company hopes to implement within the next year. The easier of the two is a probiotic supplement, which only needs to be tested and “generally recognized as safe” by the FDA. This is the same name given to any other supplement that offers general health benefits but makes no therapeutic claims, such as that it cures anything.

These supplements will first be targeted for pediatric use, as infants are increasingly born with defective gut microbiomes due to things like C-sections, antibiotics, and formula. As helpful as these things are, they seem to work against the gut, which can contribute to a huge increase in allergies, among other things. A shelf-stable liquid probiotic supplement can be a standard addition to any infant’s baby bag.

An employee of Persephone works in the company’s laboratory.

More testing of the infant gut biome is needed, and Persephone will announce a major new collaboration in infant health and a new nationwide study to help collect this soon. Fortunately, “picking up baby poop is very easy,” Culler said. If anything parents have too many samples.

The company will eventually expand into older and older adults, while exploring specific applications such as IBS, inflammation and other issues that can be affected by these microbes.

Another avenue of progress, pursued in parallel with Persephone, is the use of microbes therapeutically in cancer treatment, where it is theorized that it could enhance the effects of immunotherapy drugs. This is the type that needs more serious FDA approval through clinical trials.

“We want to be in the clinic in the next year and a half. In 2024, we will definitely be there for lung cancer,” Culler said, referring to the partnership with Johnson & Johnson. “Beyond oncology, we are very interested in the gut-brain axis. these superbugs [i.e. the superhero microbes, not viruses] are important for any disease.”

There is also a new collaboration with Ginkgo Bioworks for new synthetic biotechnologies and ARGONAUT, a large-scale study of the gut-immune axis to search for biomarkers for cancer detection and treatment. The company has a lot on its plate, so don’t be surprised if you start seeing Persephone-powered studies pop up with some frequency.

Progress raised a $15 million round led by First Bight Ventures and Propel Bio Partners, Y Combinator, Fifty Years, Susa Ventures, the American Cancer Society’s BrightEdge Fund, Pioneer Fund- and ZhenFund with participation.



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