“It’s my favorite conversation. In fact, there’s no family gathering or outing with friends where we don’t talk about my poop,” says Adela Garre. “I love people’s reactions when I tell them I’ve been donating stool for four years. They’re usually amazed,” explains this 32-year-old Barcelonian.
Adela is part of the regular donor group at the Hospital Clínic of Barcelona, one of the pioneering centers in performing fecal microbiota transfer (FMT) in Spain. Along with the Bellvitge University Hospital (Barcelona), they’ve established the Catalonia Microbiota Bank, the first of its kind in Spain and one of the few in Europe.
“We use stool donations to perform treatments in our hospital or to serve other hospitals with patients eligible for a fecal microbiota transplant,” explains Andrea Aira, technical director of the Microbiota Bank.
This therapy involves obtaining gut microbiota from a stool sample of a healthy donor and inserting it into a patient with an imbalanced gut microbiota. In most cases, this is done through a colonoscopy, although it can also be carried out through nasogastric tube, enema or oral freeze-dried capsules.
Samples obtained from donors are frozen and kept in quarantine for two months. Hospital Clínic of Barcelona.
In Spain, fecal microbiota transplant is currently only approved for recurrent infections caused by Clostridioides difficile, an opportunistic bacterium responsible for diarrhea in hospitalized patients. This means it usually does not infect healthy people but can cause an infection in people with an altered gut microbiota and/or a weakened immune system.
This bacterium can lead to severe and life-threatening damage to the colon especially in certain cases: recent and long-term hospitalization, advanced age (>65 years old), impaired immune response (e.g., during chemotherapy), and use of antibiotics for long periods of time. These infections are usually be first treated with antibiotics; however, between 20 and 30% of patients relapse and must take antibiotics again. In these cases of recurrent infection, fecal microbiota transfer has proven to be much more effective.
“When we have patients who have relapsed once or twice, before treating them again with antibiotics, we offer them the possibility of undergoing an FMT, which has a very high success rate, and they all accept,” explains Aira. At Hospital Clínic, FMTs are performed via colonoscopy, which “is effective in 9 out of 10 cases,” notes Begoña González, gastroenterologist at this hospital who performs the fecal transfer procedure. “Lyophilized capsules are slightly less effective, around 75-80%, because the capsule formation process itself causes some bacteria to not survive,” comments this specialist, although she points out that “the difference in success rate between procedures is small, and capsules save you from the invasive colonoscopy.”
Currently, research in FMT focuses on designing increasingly efficient capsules, not only lyophilized ones. For example, Aira, from Hospital Clínic, in her doctoral thesis, created a new formulation of patented and licensed capsules, now being exploited by a Scottish company conducting clinical trials with patients with hepatic encephalopathy and bone marrow transplants that reject.
The most common procedure for performing a microbiota transplant is colonoscopy, but capsules are increasingly being researched. Although they are slightly less effective, they are less invasive. Bellvitge Hospital.
“It’s like a pellet (small droppings of feces) of intestinal microbiota to which we add excipients that remove moisture from the sample to maintain stable microbiota,” says this microbiologist, adding that this procedure to obtain microbiota capsules “is easier and cheaper than lyophilization.”
Both at Clínic and Bellvitge, they began researching FMT in 2018 to treat C. difficile patients, but they already have various studies underway to apply it to other pathologies, such as treating recurrent urinary tract infections in women or to decolonize the intestinal tract of patients from multiresistant bacteria before surgery. In other centers, this procedure is also being researched for pathologies such as obesity, type 2 diabetes, Alzheimer’s, and other neurodegenerative diseases.
And although it seems new, this treatment was already used in China in the 4th century to treat severe food poisoning and diarrhea, using a stool suspension known as “yellow soup.”
Donors, the key to success
The donor selection process is one of the keys to the success of the Catalonia Fecal Microbiota Bank. To donate stool, individuals must be between 18 and 50 years old and pass a series of controls, blood tests, and screenings. “We take maximum precautions because it is essential to guarantee the safety of the product we are transferring. Right now, the relationship between intestinal microbiota and countless pathologies is being studied. That’s why we reject many people and only keep between 4 and 5% of potential donors,” says Aira.
Donors send their stool in a kit designed for this purpose, to the hospital where it is prepared, frozen, and quarantined. Two months after donation, if the donor successfully passes all the tests again, the samples are thawed and prepared for use.
At Bellvitge, they process stool samples from donors and subject them to a lyophilization process. Bellvitge Hospital.
“During the week, I try to do my business in the sample collection kit they give us and notify them. Shortly after, they come to pick it up, and that’s it. It doesn’t require any effort on my part, and I know I’m helping other people,” says Adela.
Both at Clínic and Bellvitge, they obtain about 230 doses annually, respectively. Now, these two pioneering centers in FMT in Spain are working to try to create biomarkers that allow evaluating the quality of a donation.
“It’s very rewarding when the hospital sends us a message informing us of how many treatments have been possible with our stool,” acknowledges Adela, who undergoes rigorous health tests and checks periodically to ensure excellent health. “I’m hyper-controlled; I know I’m super healthy,” she jokes.
Leave it to the pros: don’t try it at home
The process of screening and monitoring stool donors is extremely strict to ensure that no pathogenic microorganisms are transplanted to the recipient. Therefore, it should always be done under medical supervision and never on one’s own initiative. “We have to be extremely cautious and prudent because we could transmit a predisposition to develop a disease, for example,” points out Jordi Guardiola, head of the digestive system service at Bellvitge University Hospital.
Guardiola emphasizes the importance of having a public Microbiota Bank, “because it guarantees the traceability of the samples.” He explains that “we have donors and recipients very well-identified, whom we follow for 30 years, so if any of them develops a disease at any time, we can compare their microbiotas and try to see if it’s involved.”
For Guardiola, moreover, this bank opens the door for local researchers to advance knowledge about the relationship between microbiota and various pathologies using the samples it holds. “In the near future, FMT will be approved to treat many other diseases and also to improve the effectiveness of treatments such as immunotherapies.” FMT is poised to be a true revolution in medicine.
Yet for all the excitement, scientists still know little about how FMT works. To complicate matters further, a gram of stool contains a staggering mix of microorganisms that varies enormously from one person to the next. Potential risks of undefined microbiota transplants include transmitting infectious microorganisms from the donor, increasing susceptibility to diseases associated with gut microbiota composition (e.g., obesity and even mental disorders), and transmitting antibiotic resistance genes present in apparently harmless gut microorganisms. These risks should be weighed in the context of the potential hea benefits of this treatment.
