Seeding a Probiotic Revolution
Ditch the yogurt. Toss out your sauerkraut. Chuck your kefir, your kombucha, your kimchi. There’s a new probiotic in town — Ara P. Katz and Raja Dhir, co-founders of Seed Health, claim that taking just two of their forest green capsules daily on an empty stomach will support digestive function and make you feel strengthened gut barrier, healthy skin, and of course, more regular shits, all for a $50 monthly delivery subscription.
The world of probiotics is a Wild West, dominated by nutritional companies that often make unregulated, hyperbolic claims. Seed Health, however, purports to be driven not by sensational promises but by scientific testing and clinical trials.
The company, informed by an advisory board that boasts many Harvard Medical School affiliates, including Maurizio Fava and George M. Church, employs a hybrid structure at the intersection of academia and biotech. Early developmental research is published in peer-reviewed publications, while translational work is conducted through randomized clinical trials. This unique approach has garnered attention from investors — in April 2021, Seed Health procured $40 million.
“Our philosophy and model has always been to seek out the best science in this space and to collaborate from the point of discovery with the scientists,” Dhir says.
Harvard Human Evolutionary Biology professor Rachel Carmody, who conducts research in nutritional microbiology and is unaffiliated with Seed Health, finds reassurance in the company’s commitment to science. “I approach probiotic companies with a skeptical eye,” she says. “The way that they describe the microbiome [on their website] is, coming from a scientist’s perspective, more responsible than what I’ve seen from other companies. It gives me faith that they will communicate what they do and do not know.”
Katz echoes concerns about probiotic companies making false claims — she realized this trend during her pregnancy and breastfeeding experience, which served as a catalyst for starting the company.
“Between the algorithms of the internet and all the unsolicited advice, I was very fascinated by how ungrounded so much of the products and information that I was receiving [were], even, in some cases, from practitioners,” Katz says.
The start-up has been working tirelessly ever since, in what Dhir calls “total immersion,” to create the technology to put its probiotic supplement DS-01 Daily Synbiotic, short-handed “DS-01,” on the market.
Unlike traditional probiotics, DS-01 contains two nested capsules. The nucleus holds 24 bacterial strains that the team believes mirror the function of most bacteria in a human gut microbiome, while the outer shell is filled with a prebiotic formula designed to boost the bacteria’s activity once it enters the gut. This precise construction is supposed to deliver the bacterial cocktail to the right spot in the gastrointestinal tract.
The company also recently launched the PDS-08 Pediatric Daily Synbiotic, or just “PDS-08”, a powder parents can stir into their kid’s’ food that contains nine strains of bacteria and five grams of fiber.
Carmody emphasizes the importance of consumer transparency, remarking that “You want to make sure that the company actually is giving you the actual strain that they say they are giving you on the label,” she says. “Historically, in the probiotic sphere, that has not been the case.”
Pieter A. Cohen, a general internist who directs the Supplement Research Program at the Cambridge Health Alliance, says he’s not easily convinced by any supplement company’s claims about what’s inside their capsules.
“You’re completely at the mercy of the manufacturer,” he says. “The FDA does no testing of these products; the stores do no testing of these products.” Through his research, he’s found serial incidences of companies falsifying information on labels, causing harm to consumers.
To be labeled true “probiotics,” rather than nutritional supplements, products must demonstrate health benefits. Seed Health was granted FDA acceptance to move forward with clinical testing in patients — demonstrating promising signs of its products’ efficacy.
Currently, it’s running a Phase 2 clinical trial at Beth Israel Deaconess Medical Center to see if patients with Irritable Bowel Syndrome feel any symptom improvement from taking the DS-01 supplement. Another study explores whether DS-01 could restore healthy microbiota after disruption by antibiotics. The results from both of these trials are expected to be released later this year, according to Dhir. Aside from DS-01, Seed Health has also completed a promising trial of PDS-08 in constipated children.
For Dhir, the end goal of these studies is to gain FDA approval, which would elevate the product’s status to a drug with proven clinical benefits.
When DS-01 launched, Seed Health was not initially planning on conducting clinical trials, but they started to explore the possibility of testing efficacy upon receiving positive feedback from their consumers with IBS who had seen improvement in their symptoms.
“Normally we would never have spontaneously thought to put a consumer probiotic consortia into an RCT [Randomized Control Trial] for IBS. That’s just not typical,” Dhir says. He explains that it was “partially motivated by knowing the mechanism of action, but partially motivated by some strong feedback that we got voluntarily from people who had tried many, many different interventions with that condition, and this was the one that was efficacious.”
While Seed Health markets DS-01 for all “humans ages 18+” regardless of health status, its FDA status as an investigational new drug is to evaluate its impact on patients with IBS. Though it is also being studied in other clinical trials, this raises concerns for Cohen, who says trials for such an early stage and small sample size demonstrate little about the product’s true nature.
“In the normal drug development stage, [a Phase 1 trial] that would just be like a very, very, very preliminary thing before it was seeing the light of day,” Cohen says.
Still, Cohen notes that studying the impact of the supplement is important to expanding the field.
“I really applaud any high-quality studies of probiotics, because there’s definitely big potential for health benefits,” he adds.
According to Gyorgy Baffy, chief of gastroenterology at the VA Boston Healthcare System and associate professor at HMS, dietary supplements are often band-aid solutions to symptoms that would see greater resolution with changes in diet, exercise, and other lifestyle habits. In his experience treating GI issues like IBS, Baffy has observed that patients are drawn to medication and supplements.
“They say, ‘Pill, pill, pill, because then I don’t have to change anything. Then I just sit back and relax, and give me that pill and it will take care of everything for me,’” he parodies. “Rather than thinking through what you don’t do well in your life.”
He approaches supplements with low expectations when patients inquire about them. “I usually tell my patients, when they come up with probiotic therapy, that this might not work. It's worth a shot; it probably won’t hurt,” Baffy says.
Recognizing the importance of people getting more involved in their personal health, two years ago, Seed Health launched a digital campaign called #giveashit where people sent pictures of their poop as a citizen science initiative to advance research at the intersection of artificial intelligence and the gut microbiome.
While Seed Health adopts a more “biotech” structure, as Dhir calls it, in the research and development process, this campaign is evidence of a marketing strategy that encourages an intimate connection between humans and science.
“One of the things we always wanted to do is really shapeshift how science can show up in the world in a way that can feel really humanistic, spiritual, beautiful, accessible, and digestible — no pun intended,” Katz says.
Seed Health also used its social media presence to bolster recruitment for its clinical trials.
“In combination with the native and existing network, as well as us using digital marketing techniques to actually access and recruit patients directly that are geo-located within the Boston area, we were able to leverage one of our company’s core capabilities to increase clinical trial recruitment,” Dhir says.
The results of the trial will need to show major improvement to prove that the placebo effect is not responsible for improvements in IBS symptoms. Background influences like their doctor’s bedside manners or messaging in advertising might prime patients for a certain clinical response to the treatment.
“You really have to shoot something big to surpass that 40, 50 percent placebo effect that we see, which happens just because you care, because you listen to the patient, because the patient is selected for something that potentially might help,” Baffy says. “That is actually paralyzing many randomized control trials in the field.”
In its description of the trial, Seed Health and its collaborators at Beth Israel acknowledge that the potency of the placebo effect ranges from 16 to 71 percent in the IBS population.
Instead of addressing these concerns about clinical trials, some probiotic companies forgo the process altogether, exploiting their status as an unregulated nutritional supplement to avoid proving their claims. Though they cannot be labeled as “probiotics,” current U.S. Food and Drug Administration regulations allow nutritional supplements to be sold over the counter and online without undergoing testing. In fact, they’re classified as a “food” by the FDA, says Aaron S. Kesselheim, a professor at HMS and former member of the FDA advisory committee.
“You can go to Whole Foods or CVS or whatever, and you’ll see rows and rows of nutritional supplements and products that are sold without clinical testing,” Kesselheim says. “As long as they’re not making trumped up or puffed up claims about what the product can do without having demonstrated that in any kind of rigorous way, then it’s allowed.”
Recent advances in the potency of nutritional supplements may be a call to action for the FDA to rethink how it regulates probiotics and other supplements, as well as help patients and physicians wade through the muddle of claims to find products that really work.
Regardless of how far Seed Health gets in its mission to reimagine human health and environmental systems through probiotics, Baffy is certain that biotech and supplement companies like it have set the course in motion for a field that’s only getting started. Baffy, who finished his medical training in Hungary in 1980, remembers a time before the concept of microbiota entered into clinical and scientific jargon. Now, he says, knowledge of the field is spreading.
The future looks good for prokaryotes: as it’s growing and developing DS-01 and PDS-08, Seed Health is initiating Phase 1 trials this year for a new probiotic for vaginal health that prevents sexually transmitted infections. If it is successful, Dhir claims it will be “one of the greatest breakthroughs in women’s health and reproductive biology.”
Beyond DS-01 and investigating the vaginal microbiome, Seed Health is also invested in saving bee colonies and exploring how the gut microbiome recovers after alcohol consumption, which Katz postulates is “top of mind for college students.” From its clinical trials to its consumer connections, Seed Health bills itself as a company committed to science, and its niche is only expanding.
“I find it difficult to believe how for so long, we ignored the microbiota, and it’s refreshing to see that over the past 15, 20 years, [we] made this recognition that, ‘Hey, these little bodies are there for a reason, and we really should pay more attention to them than what we have been,’” Baffy says. “I think it’s very exhilarating.”
Corrections: June 11, 2022
A previous version of this article incorrectly stated the company Seed Health claims its DS-01 product will lead to improved digestive support. In fact, the company claims only that its product will support digestive function, not lead to an improved or changed state.
A previous version of this article misstated the names of Seed Health’s PDS-08 Pediatric Daily Synbiotic product and its DS-01 Daily Synbiotic product.
A previous version of this article incorrectly stated that clinical testing of Seed Health’s DS-01 product has centered around observing its effect in IBS patients. In fact, DS-01's FDA status as an investigational new drug is to evaluate its impact on patients with IBS, but it is also being evaluated in other clinical trials.
Correction: April 27, 2022:
A previous version of this article incorrectly stated Gyorgy Baffy’s title. He is an associate professor at Harvard Medical School.
— Magazine writer Dina R. Zeldin can be reached at dina.zeldin@thecrimson.com.