Category Archives: fecal transplant

Microbiota Transfer Therapy improves gastrointestinal and autism symptoms

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Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study

New research suggests a link between the microbiome and autism spectrum disorder.  Using a protocol that involved a fecal microbiota transplant (FMT) resulted in an improvement in both gastrointestinal symptoms but also behavioral improvements.  This small study is important as it reproduces the results of other adult studies that have shown an improvement in psychological symptoms following FMT.  It provides yet more evidence of a gut-brain connection and should encourage others to explore this important connection.

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Nutritional Keys for Intestinal Barrier Modulation

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Abstract

The intestinal tract represents the largest interface between the external environment and the human body. Nutrient uptake mostly happens in the intestinal tract, where the epithelial surface is constantly exposed to dietary antigens. Since inflammatory response toward these antigens may be deleterious for the host, a plethora of protective mechanisms take place to avoid or attenuate local damage. For instance, the intestinal barrier is able to elicit a dynamic response that either promotes or impairs luminal antigens adhesion and crossing. Regulation of intestinal barrier is crucial to control intestinal permeability whose increase is associated with chronic inflammatory conditions. The cross talk among bacteria, immune, and dietary factors is able to modulate the mucosal barrier function, as well as the intestinal permeability. Several nutritional products have recently been proposed as regulators of the epithelial barrier, even if their effects are in part contradictory. At the same time, the metabolic function of the microbiota generates new products with different effects based on the dietary content. Besides conventional treatments, novel therapies based on complementary nutrients are now growing. Fecal therapy has been recently used for the clinical treatment of refractory Clostridium difficile infection instead of the classical antibiotic therapy. In the present review, we will outline the epithelial response to nutritional components derived from dietary intake and microbial fermentation focusing on the consequent effects on the integrity of the epithelial barrier.

Front Immunol. 2015; 6: 612.

Figure 1 - Diet Modulation of Intestinal Permeability - De Santis et al.

Figure 2 - Diet Modulation of Intestinal Permeability

 

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Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection.

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  • 1Division of Infectious Diseases, Massachusetts General Hospital, Boston2Harvard Medical School, Boston, Massachusetts3Division of Infectious Diseases, Boston Children’s Hospital, Boston, Massachusetts.
  • 2Harvard Medical School, Boston, Massachusetts4Department of Gastroenterology and Nutrition, Boston Children’s Hospital, Boston, Massachusetts.
  • 3Division of Infectious Diseases, Massachusetts General Hospital, Boston.
  • 4Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • 5Harvard Medical School, Boston, Massachusetts6Division of Gastroenterology, Massachusetts General Hospital, Boston.
  • 6Division of Infectious Diseases, Massachusetts General Hospital, Boston2Harvard Medical School, Boston, Massachusetts.

Abstract

IMPORTANCE:

Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use.

OBJECTIVE:

To evaluate the safety and rate of resolution of diarrhea following administration of frozen FMT capsules from prescreened unrelated donors to patients with recurrent C. difficile infection.

DESIGN, SETTING, AND PARTICIPANTS:

Open-label, single-group, preliminary feasibility study conducted from August 2013 through June 2014 at Massachusetts General Hospital, Boston. Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C. difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C. difficile infection requiring hospitalization were enrolled.

INTERVENTIONS:

Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80°C (-112°F). Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months.

MAIN OUTCOMES AND MEASURES:

The primary end points were safety, assessed by adverse events of grade 2 or above, and clinical resolution of diarrhea with no relapse at 8 weeks. Secondary end points included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements.

RESULTS:

No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 patients (70%; 95% CI, 47%-85%) after a single capsule-based FMT. All 6 nonresponders were re-treated; 4 had resolution of diarrhea, resulting in an overall 90% (95% CI, 68%-98%) rate of clinical resolution of diarrhea (18/20). Daily number of bowel movements decreased from a median of 5 (interquartile range [IQR], 3-6) the day prior to administration to 2 (IQR, 1-3) at day 3 (P = .001) and 1 (IQR, 1-2) at 8 weeks (P < .001). Self-ranked health scores improved significantly on a scale of 1 to 10 from a median of 5 (IQR, 5-7) for overall health and 4.5 (IQR, 3-7) for gastrointestinal-specific health on the day prior to FMT to 8 (IQR, 7-9) after FMT administration for both overall and gastrointestinal health (P = .001). Patients needing a second treatment to obtain resolution of diarrhea had lower pretreatment health scores (median, 6.5 [IQR, 5-7.3] vs 5 [IQR, 2.8-5]; P = .02).

CONCLUSIONS AND RELEVANCE:

This preliminary study among patients with relapsing C. difficile infection provides data on adverse events and rates of resolution of diarrhea following administration of FMT using frozen encapsulated inoculum from unrelated donors. Larger studies are needed to confirm these results and to evaluate long-term safety and effectiveness.

JAMA. 2014 Nov 5;312(17):1772-8. doi: 10.1001/jama.2014.13875.

Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection

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Christine H. Lee, MD1,2,3; Theodore Steiner, MD4; Elaine O. Petrof, MD5; Marek Smieja, MD, PhD1,2,3; Diane Roscoe, MD6; Anouf Nematallah, MD4; J. Scott Weese, DVM7; Stephen Collins, MBBS8; Paul Moayyedi, MB8; Mark Crowther, MD2,3; Mark J. Ropeleski, MD5; Padman Jayaratne, PhD1,3; David Higgins, MB3; Yingfu Li, PhD9; Neil V. Rau, MD11,12; Peter T. Kim, PhD1,10

Importance  Clostridium difficile infection (CDI) is a major burden in health care and community settings. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues. Fecal microbiota transplantation (FMT) is a promising, but not readily available, intervention.

Objective  To determine whether frozen-and-thawed (frozen, experimental) FMT is noninferior to fresh (standard) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT.

Design, Setting, and Participants  Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada.

Interventions  Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema.

Main Outcomes and Measures  The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events. Noninferiority margin was set at 15%.

Results  A total of 219 patients (n = 108 in the frozen FMT group and n = 111 in the fresh FMT group) were included in the modified intention-to-treat (mITT) population and 178 (frozen FMT: n = 91, fresh FMT: n = 87) in the per-protocol population. In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group (difference, −1.6% [95% CI, –10.5% to ∞]; P = .01 for noninferiority). In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% [95% CI, –5.2% to ∞]; P < .001 for noninferiority). There were no differences in the proportion of adverse or serious adverse events between the treatment groups.

Conclusions and Relevance  Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea. Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting.

JAMA. 2016;315(2):142-149. doi:10.1001/jama.2015.18098.

 

The Excrement Experiment

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Treating disease with fecal transplants.

Some disease sufferers have benefitted from fecal transplantation, in which a healthy person’s stool is transferred to a sick person’s colon.
Some disease sufferers have benefitted from fecal transplantation, in which a healthy person’s stool is transferred to a sick person’s colon.CREDITILLUSTRATION BY OLIVER MUNDAY

One morning last fall, Jon Ritter, an architectural historian living in Greenwich Village, woke to find an e-mail from a neighbor, who had an unusual request. “Hi Jon, This is Tom Gravel, from Apt. 4N,” the e-mail began. “I wanted to check in and see if you may be open to helping me with a health condition.” Gravel, a project manager for a land-conservation group, explained that he had Crohn’s disease, an autoimmune disorder that causes inflammation of the intestinal tract along with unpredictable, often incapacitating episodes of abdominal pain and bloody diarrhea. His doctor had prescribed a succession of increasingly powerful drugs, none of which had helped. But recently Gravel had experimented with a novel therapy that, though distasteful to contemplate, seemed to relieve his symptoms: fecal transplantation, in which stool from a healthy person is transferred to the colon of someone who is sick. He hoped to enlist Ritter as a stool donor.

“I realize this is really out there,” Gravel wrote. “But I think you and your family are the nicest people in our building, and I thought I might start with lucky you.”

Bacterial composition following fecal microbiota transplantation

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Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection

Alexa Weingarden1,7†, Antonio González2, Yoshiki Vázquez-Baeza3†, Sophie Weiss4, Gregory Humphry5, Donna Berg-Lyons5, Dan Knights6,7, Tatsuya Unno7, Aleh Bobr8, Johnthomas Kang7,8, Alexander Khoruts7,8, Rob Knight2,9,10 and Michael J Sadowsky1,7*

Abstract

Background: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) that often fails standard antibiotic therapy. Despite its widespread recent use, however, little is known about the stability of the fecal microbiota following FMT.

Results: Here we report on short- and long-term changes and provide kinetic visualization of fecal microbiota composition in patients with multiply recurrent CDI that were refractory to antibiotic therapy and treated using FMT. Fecal samples were collected from four patients before and up to 151 days after FMT, with daily collections until 28 days and weekly collections until 84 days post-FMT. The composition of fecal bacteria was characterized using high throughput 16S rRNA gene sequence analysis, compared to microbiota across body sites in the Human Microbiome Project (HMP) database, and visualized in a movie-like, kinetic format. FMT resulted in rapid normalization of bacterial fecal sample composition from a markedly dysbiotic state to one representative of normal fecal microbiota. While the microbiome appeared most similar to the donor implant material 1 day post-FMT, the composition diverged variably at later time points. The donor microbiota composition also varied over time. However, both post-FMT and donor samples remained within the larger cloud of fecal microbiota characterized as healthy by the HMP.

Conclusions: Dynamic behavior is an intrinsic property of normal fecal microbiota and should be accounted for in comparing microbial communities among normal individuals and those with disease states. This also suggests that more frequent sample analyses are needed in order to properly assess success of FMT procedures.

Keywords: Short- and long-term changes in microbiota following FMT

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