For more than a decade, the first national stool bank, OpenBiome, filled a critical need, providing a product that could — often with just one dose — reverse acute Clostridioides difficile, and prevent its recurrence, but that era has definitively come to an end, leaving clinicians and perhaps tens of thousands of patients in the lurch.

In new final guidance, the FDA reaffirmed a 2013 proclamation that it views fecal microbiota transplant (FMT) as a drug, not as a human-derived product like blood or a tissue or solid organ transplant. Gastroenterologists and patient advocates had held out hope the agency might follow a blood bank type model. They met with former FDA Commissioner Marty Makary, MD, in early 2025 in a failed bid to convince the agency to adopt that approach.

The new policy heavily tips the scales toward companies that want to commercialize FMT. And it means going forward, conventional FMT — like that produced by OpenBiome — will be less available and potentially more expensive.

The agency has approved two FMT therapies that followed the drug route: Rebyota and Vowst (an oral preparation). Both are indicated only for the prevention of C difficile recurrence, only in adults. Some 500,000 Americans are infected with C difficile each year, according to the CDC. The illness kills 15,000-30,000 annually in the US.

Alexander Khoruts, MD, a gastroenterologist who has extensively researched FMT and was in the meeting with Makary, told Medscape Medical News the final FDA policy is concerning. “Nobody needs to make big money out of this,” said Khoruts, director of the Microbiota Therapeutics Program at the University of Minnesota in Minneapolis.

He’d prefer the agency’s focus to be “on safety and access,” of donor-derived material; that could have been accomplished by treating FMT like a blood transfusion.

Colleen Kelly, MD, a gastroenterologist at Brigham and Women’s Hospital in Boston, is not as gloomy. Although the two approved FMT products are more expensive than OpenBiome’s FMT, they may have widened access, at least in recurrent C difficile, said Kelly, an associate professor at Harvard Medical School in Boston.

“Doctors who previously didn’t feel like they were comfortable using an unapproved product or a stool bank now have these things that they can use, so access should theoretically be better,” Kelly told Medscape Medical News.

But even Kelly acknowledged that access to FMT is curtailed for children and for those who have acute severe disease or who are uninsured.

The FDA forced OpenBiome to stop shipping in December 2024. That has been “a huge blow” for children, said Stacy A. Kahn, MD, director of fecal microbiota transplantation at Boston Children’s Hospital in Boston. Many “are left with inadequate treatment options and are failing standard therapies,” said Kahn, an associate professor of pediatrics at Harvard Medical School.

Kahn told Medscape Medical News that C difficile is on the rise for children and that pediatric patients experience higher rates of community-acquired disease for reasons that aren’t understood. Many end up with recurrent infections, Kahn said.

The FDA still allows hospitals to manufacture FMT in-house, but it is a lengthy and resource-intensive process.

And it presents safety concerns, said Kahn. OpenBiome had greater capacity to screen for potentially dangerous viruses or bacteria and a higher-level ability to follow good manufacturing practices than most hospitals, she said.

“We should be using banks for stool, just like we do for blood and other tissues,” she said. “It’s not an ideal situation to go backwards,” said Kahn.

The agency’s guidance “effectively returns programs to the pre-OpenBiome model (pre-2013), reintroducing substantial logistical barriers — donor identification, comprehensive laboratory screening, specimen processing, storage, documentation, and quality assurance,” wrote Charles B. Miller and colleagues in Current Gastroenterology Reports.

It is “one giant step backward,” they wrote, echoing Kahn’s concerns.

Severe Disease Challenges 

Both Rebyota and Vowst are approved solely in immunocompetent adults and only to prevent recurrent C difficile — the larger commercial opportunity.

They are not approved for the more dangerous severe C difficile. Rebyota — administered as an enema — could potentially be lifesaving and cost-effective in those hospitalized patients, said Khoruts. But at $9000-$10,000 per dose and with potentially no reimbursement, many hospitals do not stock the treatment, he said.

And patients might need three or more doses of Rebyota, said Kelly. That could mean “near $30,000 worth of product,” she said. In addition, there are just not enough data that Rebyota is effective for those patients, she said.

OpenBiome’s FMT was a go-to for those patients, said Kelly. That FMT — purified from a pool of donor stool — was “highly effective at turning them around from that really sick state,” she said.

The OpenBiome treatment — about $1500 a dose — wasn’t covered by insurance, but hospitals typically did not pass on the cost to patients, said Kelly. Facilities collected at least some reimbursement for the colonoscopy, she said.

Rebyota is on formulary at Brigham and Women’s Hospital, so Kelly and her colleagues at least have access for acute infections. They also can use FMT treatments produced in-house by a donor program created and maintained by Massachusetts General Hospital.

Kelly is a principal investigator on a study of FMT in severe C difficile being conducted as part of the American Gastroenterological Association’s national registry on FMT and other gut microbial therapies. The goal is to determine the best treatment protocols for patients who are very sick and to demonstrate how FMT actually works.

But enrollment drastically declined when study sites lost access to OpenBiome material. Now they aren’t sure what they should use, said Kelly.

Khoruts is working with OpenBiome to do the impossible: a placebo-controlled trial of FMT in severe disease, with the goal of steering the stool bank’s product through FDA review and approval. Having a placebo arm is ethically challenged, given that one FMT treatment tends to be lifesaving, said Khoruts.

But in the study, all enrollees will receive standard antibiotics. One arm will receive FMT, and the other will receive a placebo. If a patient does not improve after two administrations, they will be moved to an open-label arm to receive more treatment, including FMT.

Few Options for Children

Some 20,000 children acquire C difficile each year in the US, and it is the “most important infectious cause of antibiotic-associated diarrhea in children,” according to a 2023 review by Debbie-Ann Shirley, MD, MPH, and colleagues. The incidence is increasing, they wrote.

Kahn said the number of infections is likely higher but that those acquired in the community aren’t tracked as intensely as those from hospitals.

Children acquire the infection from antibiotics or because they have an enteral feeding tube or are at higher risk because they are immunocompromised, have Crohn’s disease or ulcerative colitis, or cystic fibrosis. Increasingly, clinicians see children with C difficile who were previously healthy and had not taken antibiotics or been in a healthcare facility, she said.

Kahn calls herself an “early adopter of FMT.” Before OpenBiome, she prepared her own stool material and applied to FDA to administer the therapy through an investigational new drug application. But she can’t do that now; it’s too time-consuming. Brigham and Women’s Hospital is a referral center, drawing patients not just from New England but also from out of state.

OpenBiome’s material had literally been lifesaving, said Kahn. In late 2024, one young girl, who had a complex medical condition and then developed cancer, acquired C difficile after chemotherapy. She ended up in intensive care with toxic megacolon and was not a surgical candidate. Kahn was able to secure two FMT doses from OpenBiome just before it closed. Within 24 hours, the girl vastly improved and is still alive today.

“It’s been very upsetting to know that there will be other children like her who will not have the benefit of that lifesaving treatment,” said Kahn.

Some of her patients can get FMT from the Massachusetts General Hospital stool bank. But most are not eligible. The only treatment is extended courses of antibiotics. Parents also turn to home cures — from expensive probiotic cocktails to specialized diets.

The missed work and school and fear that the antibiotics won’t work take a “huge emotional toll,” Kahn said. The antibiotics also come with their own set of problems — potential long-term impacts on the microbiome and a potentially increased risk for resistance over time, among them.

Parents want a cure, said Kahn. Antibiotics are a partial treatment, whereas FMT is 80%-90% effective. Telling parents they can’t have FMT is “really devastating,” she said.

“It’s very, very hard for families to understand why the FDA made this decision,” said Kahn.

FMT Future Uncertain

While some facilities continue to make their own FMT, it is a vanishingly small number because of the resources necessary to scale up and support such a program.

At Minnesota, donors — found mostly through word of mouth — must be healthy, not be taking any illicit or prescription drugs, and have no history of disease or neuropsychiatric issues. They are intensively tested for COVID and other viruses and must fill out detailed questionnaires about habits and lifestyle with every donation. Donations are made in a supervised bathroom.

Donors “are essentially in a surveillance program,” said Khoruts. And they are not paid; the program only wants altruistic donors, he said.

The Minnesota FMT program survives largely because of philanthropic funding, he said. The program offers free treatments to 50-60 people a year for recurrent C difficile, and it also supports some 15 clinical trials.

Kelly is optimistic that more companies will pursue stool-based treatments for recurrent C difficile. They will be better, more refined, and less expensive to manufacture, she said.

But she acknowledges that for severe disease, “it’s hard to imagine that a company would want to develop a product for that market,” given its size.

That leaves a big gap. “OpenBiome was treating about 10,000 patients a year,” while the two approved products have been given to maybe 10,000 total individuals, said Khoruts. The small numbers mean “there must be significant barriers for patients,” to get the FDA-approved medications, he said.

While a low dose of vancomycin might be less expensive and just as effective at suppressing C difficile to prevent recurrence, “it’s a terrible public policy to do that, because you’re breeding antibiotic resistance,” he said.

Kahn is still scratching her head. “You’re taking away a therapy that’s safe, cost-effective, and was working well,” she said.

Khoruts disclosed having intellectual property on purification and cryopreservation of fecal microbiota for transplantation and being a co-founder of Gut-Brain-Axis Therapeutics, a company focused on the gut microbiome as a therapeutic target in autism spectrum disorders. Kelly reported having recently received advisory fees from OpenBiome and being on the Eli Lilly advisory board for obesity medications. Kahn reported being on the advisory board for the Peggy Lillis Foundation, a C difficile patient advocacy organization.

Alicia Ault is a St. Petersburg, Florida-based freelance journalist whose work has appeared in many health and science publications. You can find her on X @aliciaault and on Bluesky @aliciaault.bsky.social.