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The Expanding Role of FMT: Hope or Hype?

Restoring gut eubiosis via microbiota transplants is promising but not the all-purpose magic bullet expected by some

by Diana Swift, Contributing Writer
December 23, 2019

In January, we reported on a study by researchers from Aarhus University Hospital in Denmark showing that adding a "chaser" of fecal microbiota transplantation (FMT) was superior to antibiotic treatment with either fidaxomicin or vancomycin alone for patients with recurrent or refractory Clostridioides difficile (C. diff) infection. This follow-up describes further developments in the exciting field of FMT.

That January study reinforced already solid evidence and recent Infectious Diseases Society of America guidelines that recommend FMT as part of standard care for controlling this sometimes lethal nosocomial threat.

But along with success, some red flags began to wave. Two cases of C. diff transmission prompted a national alert from the FDA in June warning clinicians to be aware of FMT risks and to share this knowledge with prospective patients.

This alert was echoed in amplifying calls for stricter criteria and screening standards for FMT stool donors. In October, a group from Massachusetts General Hospital in Boston reported details of the two cases that prompted the FDA warning. Two immunocompromised FMT trial patients became infected with extended-spectrum beta-lactamase (ESBL)�"producing Escherichia coli the day after undergoing FMT with stool from the same donor. That suggested that in addition to stricter donor standards, the risk-benefit balance of stool transplants per se need more scrutiny. "The two reported cases represent the tip of the iceberg of that FMT-transmitted infection," one observer commented.

Also in October, researchers from another Boston group at the Massachusetts Institute of Technology released a new conceptual framework for rationally selecting appropriate stool donors based on specific variations in patients' microbiomes, a move they said would increase the chance of clinical effectiveness and reduce the chance of false-negative outcomes.

November saw the publication of a Dutch study from Leiden University Medical Center reporting the first human transmission of Blastocystis subtypes 1 and 3 from donors to patients undergoing FMT for recurrent C. diff infection. Since transmission produced no gastrointestinal symptoms and did not impact treatment outcome, however, the authors surmised that the presence of this common parasite might not disqualify an FMT stool donor. The researchers, however, did observe a non-significant trend toward an increased rate of C. diff relapses and new episodes in patients treated with stool from Blastocystis-positive donors.

The general success of FMT in C. diff has sparked interest in its use for controlling other diseases such as inflammatory bowel disease (IBD). Results have been mixed, but in January of this year a small randomized trial from the University of Adelaide in Australia found that a three-dose, one-week induction course of anaerobically prepared donor FMT was more likely to induce clinical and endoscopic remission in active mild-to-moderate ulcerative colitis at week 8 than was autologous FMT. The study also showed a significant difference in favor of donor FMT for clinical remission and clinical response.

In May, results from Boston researchers in the ICON study presented at Digestive Disease Week (DDW) showed that FMT was safe and effective for IBD patients who also had C. diff infection.

Also, a small pilot study of primary sclerosing cholangitis patients by the same Boston group found FMT reduced alkaline phosphatase levels in 30% of patients and safely increased microbial diversity in all patients as early as week 1.

In liver cirrhosis patents with recurrent hepatic encephalopathy, a small randomized trial published in May by investigators from Virginia Commonwealth University in Richmond suggested FMT after antibiotic therapy might prevent long-term recurrence. The study also found long-term improvement in cognitive function.

Increasingly, FMT delivered to the gut is being tested as a gastrointestinal portal for treating metabolic and other diseases that are not specifically gastrointestinal. Also at DDW, researchers from Brigham and Women's Hospital, Boston, presented results from the first randomized controlled study of FMT in obesity showing that FMT capsules from a lean female donor changed the composition of the gut microbiota of otherwise healthy obese patients �" opening the door to a possible new and much-needed stratagem for weight loss. FMT did not, however, improve levels of glucagon-like peptide-1 or alter body weight. Future studies will likely shed light on the role of the intestinal microbiome in obesity and lead to targeted therapies.

In still another DDW presentation, slightly greater numeric improvements in insulin sensitivity emerged in obese patients given FMT versus placebo, although the improvements were not statistically significant. The authors concluded that this procedure alone may not be enough to significantly help most obese patients.

Not all the studies have been positive. In July, researchers from Albert Einstein College of Medicine in New York City reported disappointing results in a randomized trial of FMT for diarrhea-predominant irritable bowel syndrome. FMT failed to improve symptom severity, quality of life and depression scores, or Bristol stool form scale values.

In contrast, at October's United European Gastroenterology Week in Barcelona, investigators in a randomized, double-blind, placebo-controlled study from Norway's University of Bergen observed that FMT using a single "super donor" with a stellar microbial signature was effective and well tolerated for various types of irritable bowel syndrome. It resulted in high rates of clinical response and marked improvement in symptoms.

Acknowledging the importance of the gut-brain axis, researchers are also investigating the FMT for other microbiome-associated conditions such as Parkinson disease. In June, a Chinese group outlined the promising case of a patient with Parkinson's and constipation whose evacuation difficulty and tremors improved after FMT.

And at the University of Ghent in Belgium, the first randomized, double-blind, placebo-controlled trial of FMT in Parkinson patients is winding down at year's end. The analysis will report soon on the effects of gut dysbiosis and restoration of gut homeostasis on the development and progression of Parkinson's disease.

Central to the success of all types of FMT trials may be the selection of ideal stool providers �" the "super donors" �" with favorable microbiota profiles optimally matched to the diseases and patients under study. Although it's early days and FMT is still in its infancy, such donors may prove to be elusive recruits over the long term.

https://www.medpagetoday.com/gastroenterology/generalgastroenterology/84089?xid=nl_mpt_SRGastroenterology_2019-12-29&eun=g379602d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=GastroUpdate_122919&utm_term=NL_Spec_Gastroenterology_Update_Active

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Heather is the Administrator of the IBS Message Boards. She is the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!

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