Article Archive
January/February 2015

Frozen Fecal Microbiota Capsules Treat C Diff
By Jamie Santa Cruz
Today's Geriatric Medicine
Vol. 8 No. 1 P. 28

Fecal microbiota transplants have been highly successful in treating recurrent Clostridium difficile (C diff) infections, but their widespread use has been hampered by safety concerns and practical difficulties. However, a small study published online by JAMA in November 2014 suggests that using frozen fecal matter in capsule form is a safe and effective method of fecal transplant administration—and one that circumvents many of the logistical difficulties associated with other methods.1

The findings are important because of the increasing prevalence of C diff, says Ilan Youngster, MD, MMSc, a specialist in pediatric infectious diseases at Massachusetts General Hospital and lead study author. "It's becoming harder and harder to treat these patients with more patients failing antibiotic treatment."

The study, presented at IDWeek 2014, involved 20 patients. All had experienced at least two episodes of severe C diff requiring hospitalization, or had experienced three or more bouts of mild to moderate C diff that had not responded to a six- to eight-week course of treatment with oral vancomycin. Each patient received 15 frozen fecal microbiota capsules (prepared from donations by unrelated donors) over two consecutive days. Diarrhea was resolved in 14 patients (70%) after a single round of treatment and in four more (an additional 20%) after a second round. All remained symptom-free after eight weeks, and none experienced any serious adverse events.

This 90% overall success rate is consistent with previous reports on fecal transplants. Few controlled studies exist to date but, according to Youngster, the cure rate in case reports has always hovered between 80% and 90% regardless of the method of administration. It's a rate that he describes as "very impressive, given that most of these patients are very, very sick."

The more common methods of administration are colonoscopy, enema, or nasal gastric tube, but Youngster and his colleagues are not the first to administer fecal microbiota transplants via capsules. Thomas Louie, MD, a professor of infectious diseases and microbiology at the University of Calgary in Alberta, Canada, presented at ID Week 2013 on his use of capsules for the administration of the transplants with his patients. Of the 27 patients he had treated with the pills at that time, all were cured. (All patients had previously experienced at least four episodes of C diff).2

Obstacles to Therapy
Though they are effective, a main problem to date with all forms of fecal transplant (including capsule administration) has been what Youngster terms the "logistical nightmare" involved in collecting stool samples. Most researchers, including Louie, have relied on fresh stool donations, usually from the patients' relatives, but doing this requires identifying and then screening each donor individually. "It's not something you can do on a large scale because you need to get a donor in and process it," Youngster says. "Every time [Louie] has a patient, they need to bring a donor in, screen him, process the donation and put it in capsules, and give it to the patient all within a very short time period."

Using frozen capsules prepared from unrelated donors, as Youngster's team has done, avoids all these difficulties; donors can be identified and screened ahead of time, so their donations can be used to establish a bank of capsules that can be given to patients as needed. The capsule packaging, meanwhile, obviates the need for an invasive procedure such as a colonoscopy with its attendant safety risks. With frozen capsules, "It's like any other medication we have in stock. When we have a patient that needs it, we can just take it out of the refrigerator and give it to him," Youngster says.

Zhi-Dong Jiang, MD, DPh, an assistant professor of epidemiology at the University of Texas in Houston, agrees that capsule administration is the direction that fecal transplants are moving. "It's easier," says Jiang, who is currently involved in an unrelated study of the efficacy of fecal microbiota capsules using lyophilized product. "The patient doesn't need to come to the hospital to do the procedure. They can do it at home, just taking the pills."

As a rule, Youngster says, fecal transplants are not the first line of treatment for C diff, but most patients with multiple bouts of the infection are good candidates for the pills. Youngster has successfully treated patients from age 11 through 88 with the capsules. The only potential barrier to the use of the pills is if the patient is unable to swallow them. "It's a mouthful," he says. Since Youngster's pills are frozen, however, most patients find that they are more easily swallowed than the previous capsules used for this purpose, and he has not experienced problems so far with patients being unable to swallow them.

Significant Benefits
Not only is the use of frozen capsules safer and more convenient than using fresh capsules or administering the transplant via colonoscopy, it's also considerably more cost-effective. To begin with, Jiang notes, there is no need for a gastroenterologist. The screening labs for the donor are expensive, according to Youngster, but unlike other researchers who are using fresh stool from relatives, he can produce a large quantity of capsules for multiple patients from a single donor, reducing costs considerably. Once his team has screened a donor, they use as much stool as the donor can produce within a week. Usually, a single donor can provide a large enough sample to produce capsules for four to six patients.

Currently, fecal transplants can be performed without FDA approval, but the regulatory issues remain murky. In 2013, the FDA announced restrictive regulations that temporarily brought most fecal microbiota transplants to a halt. Those regulations have since been relaxed, but transplants are still permitted only when either the patient or the treating physician knows the donor, according to Youngster. For this reason, researchers who are currently producing capsules cannot make them available to people in cases where neither the patient nor treating physician knows the donor.

The current regulatory environment hampers the potential for commercial development, but Youngster doesn't see that as a barrier to wider use of the capsules. "It's not rocket science to produce these capsules. By publishing [this research], I'm hoping that other providers around the country will start doing the same thing," he says.

His hope is that transplants prepared from human stool will ultimately become a thing of the past. "Fecal transplants as they are today—that's not the future," he says. "The goal of everyone is to be able to grow these bacteria and make kind of a super probiotic […] without needing to use these stools."

Jiang agrees. "The product we are using right now is so crude. It's not pure enough," she says. "Right now, we only know we gave the patient some microbiota from the healthy donors, but […] what is the effective compound?" Currently, she says, it is not even known whether the active factors are bacteria or chemicals. The current thinking is that they are bacteria, but there are a huge variety of bacteria that currently cannot be cultured, leaving many unknowns.

It's unclear what unintended effects may result from altering a patient's gut microbiome through fecal microbiota transplants. "So many things are linked to the microbiome, like diabetes and overweight," Jiang says. To avoid the possibility that a fecal microbiota transplant may result in a patient developing a condition like diabetes in the future, it's critical to isolate the relevant bacteria and move away from using human stool.

Youngster shares Jiang's concerns about the ramifications of disrupting the gut microbiome, and for this reason he is wary of suggestions that fecal microbiota transplants may be useful for treating other conditions. He encourages physicians to consider fecal microbiota transplants for very sick patients with recurrent C diff, but he stresses that C diff is their only indication so far.

Youngster offers a final word of caution: warn patients about at-home treatments. "Everyone should be aware that if you go online and Google fecal transplants […], you'll find books and websites explaining how to do it at home yourself, which is definitely something we are against. This is a medical treatment and you need to screen the donor. […] It's important to talk to patients about the dangers of that."

— Jamie Santa Cruz is a freelance writer based in Englewood, Colorado.

1. Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014;312(17):1772-1778.

2. Fecal transplant pill knocks out recurrent C. diff infection, study shows. IDWeek website. Accessed November 7, 2013.