Fecal Microbial Transplantation -Evidence for Use Beyond Recurrent Clostridium Difficile

Briefly noted: GR D’Haens, C Jobin. Gastroenterol 2019; 157: 624-36. This review sums up the emerging evidence for use of fecal microbial transplantation for conditions besides recurrent Clostridium difficile infection.

Table 2 succinctly provides list of disease, types of study/evidence, and potential effect.

  • Among gastrointestinal diseases, the authors note that there is an “overall positive” effect for ulcerative colitis, “suggestive” benefits for IBS, GVHD, post-antibiotic diarrhea, constipation, and hepatic encephalopathy.  No effect has been evident with Crohn’s disease or pouchitis.
  • Among nongastrointestinal diseases, the authors note a “suggestive” benefit in autism and metabolic syndrome and “unknown” effect with psoriasis and multiple sclerosis.

My take: The review indicates a need for more studies and the need to define which factors in fecal material mediate the therapeutic effects.

Related article: OC Aroniadis. Lancet Gastroenterology and Hepatology; 2019. https://doi.org/10.1016/S2468-1253(19)30198-0. In this double-blind, randomized, placebo-controlled crossover trial in patients aged 18–65 years with moderate-to-severe IBS-D with 48 patients, FMT (capsule study) was safe, but did not induce symptom relief at 12 weeks compared with placebo.

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FDA News: FDA Warning for FMT, IB-Stim Device Approval, Teduglutide Approval

1.From John Pohl Twitter Feed:  FDA Warns of One Death Linked to Fecal Transplants (6/13/19)

An excerpt:

The consent should include, at a minimum, a statement that the use of FMT to treat C. difficile is investigational and a discussion of its potential risks.

“Two immunocompromised adults who received investigational FMT developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli). One of the individuals died,” the agency said Thursday…

Openbiome, a nonprofit stool bank based in Cambridge, MA, told Focus: “We are saddened to hear of the recent patient death due to an infection from a multi-drug resistant organism (MDRO) transmitted through a fecal transplant. OpenBiome material was not involved. OpenBiome screens its donors and fecal transplant material for MDROs and related risk factors, and this serious event further highlights the importance of rigorous screening and clinical oversight for all fecal transplant procedures.”

 2. FDA approval for IB-stim (a.k.a. Neuro-stim) device.

Link:: FDA permits marketing of first medical device for relief of pain associated with irritable bowel syndrome in patients 11-18 years of age

An excerpt:

IB-Stim treatment resulted in at least a 30% decrease in usual pain at the end of three weeks in 52% of treated patients compared to 30% of patients who received the placebo, and at least a 30% decrease in worst pain in 59% of treated patients compared with 26% of patients who received the placebo.

:Kovacic K1Hainsworth K2Sood M1Chelimsky G1Unteutsch R1Nugent M3Simpson P3Miranda A4. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.

Link to abstract of relevant study:  Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial.

3. FDA Approves Gattex (Teduglutide) for Pediatric SBS

From CenterWatch: Gattex New FDA Drug Approval

Pediatric SBS: “In a 24-week pediatric study 59 pediatric patients with SBS aged 1 year through 17 years chose whether to receive Gattex or standard of care (SOC)…Based on patient-diary data, patients who received Gattex 0.05 mg/kg/day experienced a 42% mean reduction in PS volume (mL/kg/day) from baseline (-23 mL/kg/day from baseline). At week 24, 38% of patients (10/26) were able to reduce PS infusion by at least 1 day per week. Patients reduced their PS infusion time by 3 hours per day on average compared to baseline.”

Related blog post: Teduglutide for SBS

Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL, O’keefe SJ, Forbes A, Heinze H, Joelsson B Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology 2012 Dec;143(6):1473-1481

Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O’Keefe SJ Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut 2011 Jul;60(7):902-14.

Latest News: ‘Georgia Girl Saved by Fecal Transplant’

For those not able to see the live presentation…

GI Care for Kids physician, Jeff Lewis, helped bring fecal microbiota transplant (FMT) to Georgia. Here’s a success story from Fox5 Atlanta from August 31, 2015.  Here’s the link:

Georgia Girl Saved by Fecal Transplant  This link includes a 4:08 video and written summary as well.

From Twitter:

Screen Shot 2015-08-31 at 6.38.42 PM

 

 

 

OpenBiome -Nation’s 1st Human Stool Bank

From NY Times: http://t.co/LIIk4JNMfl

An excerpt:
Around noon on a recent Friday, Donor Five, a healthy 31-year-old, walked across M.I.T.’s frigid, wind-swept campus to a third-floor restroom to make a contribution to public health.

Less than two hours later, a technician blended the donor’s stool into preparations that looked like chocolate milk. The material was separated and stored in freezers at an M.I.T. microbiology lab, awaiting shipment to hospitals around the country. Each container was carefully labeled: Fecal Microbiota Preparation.

Nearly a year ago, Mark Smith, a 27-year-old doctoral candidate, and three colleagues launched OpenBiome, the nation’s first human stool bank. Its mission: to provide doctors with safe, inexpensive fecal material from screened donors to treat patients with Clostridium difficile, a gastrointestinal infection that kills at least 14,000 Americans a year.

“People are dying, and it’s crazy because we know what the solution is,” Mr. Smith said. “People are doing fecal transplants in their basements and may not be doing any of the right screening or sterile preparation. We need an intermediate solution until there are commercial products on the market.”…

The bacteria are increasingly resistant to conventional treatments. But researchers have discovered an alternative: A donor’s stool can be transplanted in the intestine or colon of a sick patient via an enema, colonoscopy or nasogastric tube. The healthy bacteria fight off C. diff and re-establish a normal community in the gut.

A study published last year in The New England Journal of Medicine found that fecal transplants were nearly twice as effective as antibiotics in treating patients with recurring C. difficile.

But where to get healthy donor stool? For doctors, it’s a tedious, time-consuming process, and some patients turn awkwardly to relatives or friends. Since September, OpenBiome has delivered more than 135 frozen, ready-to-use preparations to 13 hospitals. The nonprofit project fields dozens of requests from doctors, hospitals and patients every week. (The preparations are not sent directly to patients.) 

Carol Capps, 75, a retired nurse in Clemmons, N.C., had been in and out of hospitals for months with a C. diff infection that was not going away despite multiple courses of antibiotics. After a recurrence, her doctor suggested OpenBiome, and she received a fecal transplant. By that afternoon, Ms. Capps said, she felt like a new person and has been healthy since…

Because of the legal ambiguity, some researchers are not preparing fecal microbiota for sale (usually at cost) …

At the same time, Mr. Smith and Eric J. Alm, an M.I.T. microbiologist and adviser to OpenBiome, said the F.D.A.’s classification of fecal transplants as drugs hinders research into their possible uses to treat inflammatory bowel diseases and obesity.

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