Oral capsule as effective as invasive procedures for delivery of fecal transplant

 

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A noninvasive method of delivering a promising therapy for persistent Clostridium difficile (C. difficile) infection appears to be as effective as treatment via colonoscopy or through a nasogastric tube. In their JAMA report, receiving early online release to coincide with a presentation at the Infectious Diseases Society of America's ID Week conference, investigators from Massachusetts General Hospital (MGH) report that oral administration of the therapy called fecal microbiota transplant (FMT) in acid-resistant capsules was as successful as more invasive methods in eliminating recurrent diarrhea caused by C. difficile.

"Numerous reports have shown that FMT is effective in treating active C. difficile infection and preventing recurrences in patients whose infections failed to respond to standard treatments," says Ilan Youngster, MD, MMSc, a fellow in Pediatric Infectious Diseases at MGH and at Boston Children's Hospital, corresponding author of the JAMA report. "The procedures that have been used before -- colonoscopies, nasogastric tubes, even enemas -- all have potential risks and discomforts for patients. The use of capsules simplifies the procedure immensely, potentially making it accessible to a greater population."

Certain strains of C. difficile -- which currently causes about 250,000 hospitalizations and 14,000 deaths each year in the U.S. -- have become highly resistant to treatment, leading to a 30 percent treatment failure rate in patients infected with those strains. Since antibiotic therapy also kills off the normal population of beneficial intestinal microbes that can keep pathologic species in check, antibiotic therapy could actually make the situation worse. FMT is believed to restore the normal balance of beneficial microbes, and studies in animals and humans using fresh fecal material -- usually delivered by colonoscopy -- have had success rates around 90 percent.

Earlier this year the same MGH research team showed that delivering frozen fecal material for FMT either by colonoscopy or nasogastric tube was equally effective. Using frozen material offers the potential of maintaining a bank of frozen samples from donors prescreened for any health issues, reducing the risks of transmitting new infections and the need to recruit and screen donors for each patient. The current study was designed to investigate whether delivering FMT orally through capsules designed to open upon reaching the small intestine would be just as effective.

Conducted at MGH, the study enrolled 20 individuals ages 11 to 84 with persistent or recurrent C. difficile infection. Stool samples were gathered from healthy adult volunteers who had been comprehensively screened for infectious diseases and avoided eating common allergens for several days before donating. The samples were filtered, diluted, screened, placed into capsules and frozen for four weeks to enable retesting of donors for important viral infections. On two consecutive days each participant received 15 FMT capsules, which most of them ingested within a few minutes. If their symptoms did not improve within 72 hours, they were offered a second course of treatment with material from the same donor.

Of the 20 study participants, 14 had complete symptom resolution after a single treatment and no recurrence during the next eight weeks. The other 6 received a second treatment about a week after the first, and in 5 of them symptoms resolved. In addition to the single patient whose symptoms didn't respond to two courses of treatment, one of the participants whose infection responded to the second course had a recurrence within the eight-week follow-up period, resulting to an overall success rate of 90 percent for the study group. Participants who needed a second treatment were generally in poorer health -- including more serious C. difficile-associated symptoms -- than were those whose symptoms resolved after a single two-day treatment.

"This small investigation was designed to be a pilot study and provides preliminary data supporting the safety and effectiveness of this approach," says Elizabeth Hohmann, MD, of the MGH Infectious Diseases Division, senior author of the report and an associate professor of Medicine at Harvard Medical School. "More experience and larger studies are needed to determine the long-term safety and efficacy, and further investigation should help determine the most effective microbial mixes for either oral or procedural administration."

Youngster adds, "While we are striving to make this treatment more accessible to patients, it's important to remind people of the potential dangers of attempting 'home brew' FMT using fecal material from family members or friends. Many people can be carriers of bacteria, viruses, and parasites that are shed in their stools but have no symptoms. It's not enough to know your donor and just ask how he or she feels, as some websites suggest. In any form, this procedure should only be performed under strict medical supervision with material from thoroughly screened donors."

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Story Source:

The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.

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Journal Reference:

1. Elizabeth L. Hohmann, MD et al. Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection. JAMA, October 2014 DOI: 10.1001/jama.2014.13875

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Cancer-Detecting Yogurt Could Replace Colonoscopies

 

Engineered yogurt bacteria could make detecting colorectal cancer and other diseases as simple as a pregnancy test.

• By Kevin Bullis on October 2, 2014

Why It Matters

One in 20 people in the United States develops colorectal cancer.

The strips of paper shown here can be used to detect synthetic biomarkers tied to diseases such as colorectal cancer. The lines indicate the presence of such biomarkers in urine.

A spoonful of yogurt could soon offer a cheap and simple way to screen for colorectal cancer.

Sangeeta Bhatia, a professor at MIT, is working to replace costly and uncomfortable colonoscopies and MRIs with a helping of yogurt followed by a urine test—a cheap method that could improve the early diagnosis of colorectal cancer.

Bhatia is developing synthetic molecules that can be introduced into the body via yogurt, and will interact with cancer in a way that produces telltale biomarkers. These molecules can then be detected easily when passed in urine.

Bhatia previously developed nanoparticles that find their way to tumors, and are then broken into smaller pieces by enzymes produced by the cancer. The broken up particles are small enough to be collected and concentrated by the kidneys, after which they are excreted.

The first iteration of the technique involved the use of lab instruments to analyze urine and find the telltale markers. Now Bhatia has developed a paper-based urine test—like the one you’d use for pregnancy. So far this test has been demonstrated in mice for colorectal cancer and liver fibrosis.

The nanoparticle work, described in a paper earlier this year, requires an injection (see “A Paper Diagnostic for Cancer”). In new, as-yet-unpublished work, Bhatia is developing a way to deliver the nanoparticles by modifying a type of bacteria found in yogurt. The bacteria produces the nanoparticle biomarkers by interacting with a tumor.

Bhatia hopes the approach will “transform diagnostics,” and says she’s in the process of forming a company to commercialize the approach. Because the test requires no specialized equipment, it will be particularly helpful in poor countries, she says, where few people are currently screened for common cancers. But it might also replace or augment colonoscopies.

If detected early, 90 percent of people with colorectal cancer survive for at least five years. But only 40 percent of people are diagnosed early, partly because so few people get screened, according to the American Cancer Society.

Samuel Sia, a professor of biomedical engineering at Columbia University, says Bhatia’s synthetic biomarkers are an “interesting concept” for providing easy and inexpensive cancer tests. He adds that nanoparticle injections have shown good reliability—at least in mice. But without data from clinical trials, he says, “I wouldn’t say this is the solution yet.”