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Cited by 572Clostridium difficile and Clostridium perfringens researchGut microbiota and healthGastrointestinal motility and disorders

Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook

Open access
Kelly, Colleen R., Kahn, Stacy, Kashyap, Purna, Laine, Loren, Rubin, David, Atreja, Ashish, Moore, Thomas, Wu, Gary·2015·Gastroenterology
DOI 10.1053/j.gastro.2015.05.008PMC PMC4755303
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Abstract

The community of microorganisms within the human gut (or microbiota) is critical to health and functions with a level of complexity comparable to that of an organ system. Alterations of this ecology (or dysbiosis) have been implicated in a number of disease states, and the prototypical example is Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) has been demonstrated to durably alter the gut microbiota of the recipient and has shown efficacy in the treatment of patients with recurrent CDI. There is hope that FMT may eventually prove beneficial for the treatment of other diseases associated with alterations in gut microbiota, such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome, to name a few. Although the basic principles that underlie the mechanisms by which FMT shows therapeutic efficacy in CDI are becoming apparent, further research is needed to understand the possible role of FMT in these other conditions. Although relatively simple to perform, questions regarding both short-term and long-term safety as well as the complex and rapidly evolving regulatory landscape has limited widespread use. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current "whole-stool" transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future.

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Crossref · 10.1053/j.gastro.2015.05.008

Cites

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Claims the paper makes

0 of 178 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    A mouse study suggests that cefoperazone alters the fecal metabolome related to microbial function.

    “A more recent study in mice treated with the antibiotic cefoperazone suggests that antibiotic treatment alters the fecal metabolome related to microbial function.48”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Khanna, 2012, The epidemiology of community-acquired Clostridium difficile infection: a population-based study, Am J Gastroenterol source

      Not checked in the free run.

  • Premisecitation

    Patients with recurrent CDI are deficient in bacterial phyla normally dominant in the colon.

    “Indeed, studies have demonstrated that patients suffering from recurrent CDI are deficient in phyla of bacteria normally dominant in the colon6,45 (Figure 1).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Khoruts, 2010, Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea, J Clin Gastroenterol source

      Not checked in the free run.

    • cites [45] Rupnik, 2009, Clostridium difficile infection: new developments in epidemiology and pathogenesis, Nat Rev Microbiol source

      Not checked in the free run.

  • Premisecitation

    Administration of a cocktail containing a member of Lachnospiraceae was reported to cure CDI in mice.

    “and administration of a cocktail containing a member of Lachnospiraceae was reported to cure CDI in mice52.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Rea, 2010, Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • Interpretationnone given

    Published data do not show a significant difference in FMT success when donor stool is mixed with tap water, milk, or normal saline.

    “Published data do not demonstrate a significant difference in success with FMT whether the donor stool is mixed in tap water, milk, or normal saline (sterile, nonbacteriostatic), although the latter is presumed to be less likely to affect the microbiota of the donor specimen.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    FMT is beneficial in patients with severe or recurrent CDI.

    “Numerous case reports, retrospective case series and a single randomized controlled trial have demonstrated benefit of FMT in patients with severe or recurrent CDI with cure rates as high as 100% and a mean cure rate of 87–90% for the over 500 cases reported in the world literature to date.3–5”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [3] Cammarota, 2014, Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review, J Clin Gastroenterol source

      Not checked in the free run.

    • cites [4] Van Nood, 2013, Duodenal infusion of donor feces for recurrent Clostridium difficile, N Engl J Med source

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    • cites [5] Kassam, 2013, Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis, Am J Gastroenterol source

      Not checked in the free run.

  • May combine two claims. 71
  • Classified as probably not a substantial claim. 31

  • May combine two claims.

    Findingnone given

    FMT seems safe, and few short-term adverse events or complications have been directly linked to it so far.

    “Though FMT appears to be safe, with few short-term adverse effects or complications directly attributed to the procedure yet reported”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The gut microbiota is integral to human physiology and contributes to metabolism, immune function, and gut homeostasis.

    “It is now understood that the gut microbiota coevolved with the human host over thousands of years and are integral to overall human physiology, playing a pivotal role in metabolism, immune system function and maintenance of gut homeostasis.1, 2”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] Backhed, 2005, Host-bacterial mutualism in the human intestine, Science source

      Not checked in the free run.

    • cites [2] Ley, 2006, Ecological and evolutionary forces shaping microbial diversity in the human intestine, Cell source

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  • May combine two claims.

    Premisecitation

    FMT durably alters the recipient's gut microbiota, with post-transplant communities resembling the donor.

    “Moreover, the restoration of more typical microbial communities, which come to resemble those of the donor post-transplant, persists in a durable fashion after FMT.6, 7”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [6] Khoruts, 2010, Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea, J Clin Gastroenterol source

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    • cites [7] Hamilton, 2013, High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria, Gut Microbes source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Successful FMT restores members of Lachnospiraceae and other butyrate-producing organisms, supporting their potential role in outcompeting C. difficile.

    “Furthermore successful FMT restores members of Lachnospiraceae and other butyrate producing organisms supporting their potential role in outcompeting C. difficile.50”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Reeves, 2012, Suppression of Clostridium difficile in the gastrointestinal tracts of germfree mice inoculated with a murine isolate from the family Lachnospiraceae, Infect Immun source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a Netherlands RCT, duodenal infusion of donor feces resolved recurrent CDI in 81% of patients, compared with 31% for oral vancomycin.

    “This study, conducted in the Netherlands, showed duodenal infusion of donor feces to effectively resolve recurrent CDI in 81% of patients treated, compared to only 31% efficacy of a standard course of oral vancomycin.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Van Nood, 2013, Duodenal infusion of donor feces for recurrent Clostridium difficile, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The mechanisms by which FMT reduces C. difficile fitness likely include niche exclusion, nutrient competition, creation of an unfavorable nutrient milieu, antimicrobial production by healthy microbiota, and increased secondary bile acid production.

    “The mechanisms underlying decreased fitness of C. difficile following FMT still remain elusive but likely include niche exclusion, competition for nutrients and creation of a nutrient milieu unfavorable for growth, ability of members of healthy gut microbiota to produce antimicrobials that inhibit growth of C. difficile and an increase in secondary bile acid production.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    FMT has been shown to be safe, well-tolerated, and effective in young and old patients, including those with limited comorbidities and immunocompromised patients.

    “FMT has been examined in both young and old, patients with limited comorbidities as well as those considered to be immunocompromised,43 and the procedure has been shown to be safe, well-tolerated, and effective.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Youngster, 2014, Fecal microbiota transplant for relapsing Clostridium difficle infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study, Clin Infect Dis source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Oral administration of frozen fecal material is a viable alternative to endoscopic FMT, reducing cost and procedural complications.

    “They reported an overall 90% response rate making oral administration a viable alternative to the current practice of administering fecal material via an endoscopic procedure thus decreasing both cost and potential procedural complications.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Youngster, 2014, Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection, JAMA source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Decrease in Lachnospiraceae is associated with severe CDI, suggesting a protective role for members of this family.

    “Decrease in Lachnospiraceae has been associated with severe CDI suggesting a protective role for members of this family51”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Lawley, 2012, Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice, PLoS Pathog source

      Not checked in the free run.

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    Premisecitation

    A few case reports suggest FMT may be safe and effective in critically ill patients with severe CDI.

    “however a few case reports suggest that it may be safe and effective even in critically ill patients18–21.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [18] You, 2008, Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy, Ann Intern Med source

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    • cites [19] Weingarden, 2013, Resolution of severe Clostridium difficile infection following sequential fecal microbiota transplantation, J Clin Gastroenterol source

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    • cites [20] Trubiano, 2013, Faecal microbiota transplantation for severe Clostridium difficile infection in the intensive care unit, Eur J Gastroenterol Hepatol source

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    • cites [21] Neemann, 2012, Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient, Transpl Infect Dis source

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    Premisecitation

    A systematic review by Cammarota et al. found lower GI route led to higher eradication rates than upper delivery, with reported rates of 81-86% versus 84-93%.

    “In a systematic review, Cammarota et al. observed that lower gastrointestinal route (colonoscopy, enema) led to the achievement of higher eradication rates than upper delivery (gastroscopy, nasogastric or nasointestinal tube) (81–86% vs 84–93%, respectively)3.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Cammarota, 2014, Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review, J Clin Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In that RCT, FMT appeared safe with no serious adverse events.

    “Furthermore, FMT appeared safe, with no serious adverse events in these subjects.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Van Nood, 2013, Duodenal infusion of donor feces for recurrent Clostridium difficile, N Engl J Med source

      Not checked in the free run.

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    Premisecitation

    An early study found that antibiotic treatment decreased urobilinogen and fecal tryptic activity and decreased conversion of cholesterol to coprostanol.

    “An early study investigating the effect of antibiotics on gut microbiota function described decreased urobilinogen and fecal tryptic activity as well as decreased conversion of cholesterol to coprostanol following antibiotic treatment.25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Gustafsson, 1999, The effect of faecal enema on five microflora-associated characteristics in patients with antibiotic-associated diarrhoea, Scand J Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Across more than 500 reported CDI cases, FMT produced rapid response and a cure rate of nearly 90%, with negligible significant adverse events regardless of route.

    “of the over 500 cases reported to date3, FMT has demonstrated rapid response and a cure rate of nearly 90%, with a negligible significant adverse event rate, regardless of route.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Cammarota, 2014, Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review, J Clin Gastroenterol source

      Not checked in the free run.

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    Premisecitation

    A cost-effectiveness study found FMT less costly and more effective than vancomycin for initial CDI.

    “though a cost-effectiveness study showed FMT dominated (i.e. was less costly and more effective) than vancomycin for initial CDI42.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Kelly, 2014, Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients, Am J Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    FMT results in durable engraftment of new species from the donor and augmentation of species present at very low levels before FMT.

    “FMT appears to result in durable engraftment of new species from donor as well as augmentation of species present at only very low levels prior to FMT6.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Khoruts, 2010, Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea, J Clin Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    FMT is one of the most efficacious treatments for recurrent CDI, though its exact mechanism remains unclear.

    “FMT represents one of the most efficacious treatments available for recurrent CDI, though the exact mechanism of effect still remains to be elucidated.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Reported cure rates for FMT in severe or recurrent CDI reach 100%, with a mean cure rate of 87-90% across more than 500 cases.

    “Numerous case reports, retrospective case series and a single randomized controlled trial have demonstrated benefit of FMT in patients with severe or recurrent CDI with cure rates as high as 100% and a mean cure rate of 87–90% for the over 500 cases reported in the world literature to date.3–5”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [3] Cammarota, 2014, Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review, J Clin Gastroenterol source

      Not checked in the free run.

    • cites [4] Van Nood, 2013, Duodenal infusion of donor feces for recurrent Clostridium difficile, N Engl J Med source

      Not checked in the free run.

    • cites [5] Kassam, 2013, Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis, Am J Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dethlefsen et al. found that ciprofloxacin reduced microbial taxonomic diversity, richness, and evenness in three individuals, with differing magnitude among individuals.

    “Dethlefsen et al. investigated the effect of ciprofloxacin in three individuals and found reduced microbial taxonomic diversity, richness and evenness, although the magnitude of effect differed among individuals.47”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Theriot, 2014, Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection, Nat Commun source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fecal transplant from healthy individuals modified those antibiotic-induced changes, with increased appearance of coprostanol and urobilinogen.

    “Interestingly these changes were modified following fecal transplant from healthy individuals with increased appearance of coprostanol and urobilinogen.25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Gustafsson, 1999, The effect of faecal enema on five microflora-associated characteristics in patients with antibiotic-associated diarrhoea, Scand J Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Moayyedi et al., 75 patients with active UC were randomized to weekly FMT or water enema for 6 weeks, and there was a statistically significant difference in remission, the primary outcome, between groups.

    “In the study by Moayyedi et. al, seventy-five patients with active UC were randomized to a weekly FMT or water enema for 6 weeks, and there was a statistically significant difference in remission, the primary outcome, between the two groups.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [77] Rossen, 2015, Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis, Gastroenterology source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    It is difficult to infer robust conclusions about FMT safety and efficacy for IBD from these studies because they were underpowered, open-label, lacked uniform protocols and delivery, and had no control groups.

    “Unfortunately, it is difficult to infer robust conclusions about the safety and efficacy of FMT for IBD from these studies because they were under-powered, open-labeled, lacked uniformity in treatment protocols and delivery approaches, and did not include control groups.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The exact mechanisms by which gut microbiota influence obesity remain unclear.

    “The exact mechanisms by which gut microbiota influence obesity still remain to be elucidated”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Preliminary case reports of FMT enemas in UC and Crohn's disease reported clinical remission and long-term maintenance in many cases.

    “Preliminary case reports of FMT enemas in patients with ulcerative colitis (UC) and Crohn’s disease (CD) were promising, reporting that patients achieved clinical remission, and maintained remission over long-term follow-up in many of the cases61, 62”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [61] Borody, 1989, Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome?, Med J Aust source

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    • cites [62] Borody, 2003, Treatment of ulcerative colitis using fecal bacteriotherapy, J Clin Gastroenterol source

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  • May combine two claims.

    Premisecitation

    IBD dysbiosis is characterized by decreased species-level diversity, decreases in Bacteroidetes and Lachnospiraceae, and increases in Proteobacteria and Actinobacteria.

    “The dysbiosis is characterized by a decreased diversity at the species level, with notable decreases in the Bacteroidetes phylum and the Lachnospiraceae group within the Firmicutes phylum and increases in Proteobacteria and Actinobacteria.59”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Sokol, 2008, Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients, Proc Natl Acad Sci U S A source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    IBS is a widely prevalent chronic gastrointestinal disorder affecting nearly 20% of the North American population.

    “IBS is a widely prevalent chronic GI disorder affecting nearly 20% of the North American population85”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [85] Matto, 2005, Composition and temporal stability of gastrointestinal microbiota in irritable bowel syndrome—a longitudinal study in IBS and control subjects, FEMS Immunol Med Microbiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Flares of FMT in patients with both UC and Crohn's disease have been described, raising questions about safety and potential to worsen disease in some patients.

    “Furthermore, flares of FMT in patients with both UC and CD have been described,43, 75, 76 raising important questions around safety and the potential to worsen disease in some patients.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [43] Youngster, 2014, Fecal microbiota transplant for relapsing Clostridium difficle infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study, Clin Infect Dis source

      Not checked in the free run.

    • cites [75] Kelly, 2014, New diagnosis of Crohn's colits 6 weeks after fecal microbiota transplantation, Inflamm Bowel Dis source

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    • cites [76] Moayyedi, 2015, Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized, controlled trial, Gastroenterology source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    IBS is associated with significant morbidity and health care expenditure.

    “is associated with significant morbidity and health care expenditure.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [85] Matto, 2005, Composition and temporal stability of gastrointestinal microbiota in irritable bowel syndrome—a longitudinal study in IBS and control subjects, FEMS Immunol Med Microbiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In that meta-analysis, pooled remission estimates were highest in younger patients (7-20 years) and Crohn's disease patients, at 64.1% and 60.5%, respectively.

    “The pooled estimates were highest in younger patients (7–20 years old) and in patients with Crohn’s disease, with 64.1% and 60.5% achieving clinical remission, respectively.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] Suskind, 2015, Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease, Inflamm Bowel Dis source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The review found FMT was not associated with serious adverse events during short-term follow-up, but some patients experienced fever, chills, and gastrointestinal symptoms including bloating, flatulence, vomiting, diarrhea, and abdominal tenderness.

    “This review also found that although FMT was not associated with any serious adverse events during short-term follow up, a number of patients experienced fever, chills, and gastrointestinal symptoms including bloating, flatulence, vomiting, diarrhea, and abdominal tenderness.73”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] Suskind, 2015, Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease, Inflamm Bowel Dis source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    The pathophysiology of IBS symptoms is not well defined, though central and peripheral mechanisms have been implicated.

    “The underlying pathophysiology of symptoms in IBS is not well defined though both central and perpipheral mechanisms have been implicated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Transmission of enteric pathogens via FMT is an important concern but appears rare with current screening.

    “Transmission of enteric pathogens via FMT is also an important concern but appears to be rare with current screening.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [107] Kahn, 2012, Colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection in a child, Am J Gastroenterol source

      Not checked in the free run.

    • cites [108] Russell, 2014, Fecal transplant for recurrent Clostridium difficile infection in children with and without inflammatory bowel disease, J Pediatr Gastroenterol Nutr source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In an abstract-reported study, nearly 90% of FMT-treated IBS patients had improved defecation and decreased abdominal bloating, and 60% had long-term benefit from 9-19 months.

    “nearly 90% of patients who were treated with FMT had an improvement in defecation and decreased abdominal bloating after FMT with 60% showing long term benefit from 9–19 months.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [95] Hamilton MJ, Weingarden AR, Sadowsky MJ, et al. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol;107:761–767. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The second death occurred 13 days after FMT from progressive pneumonia and was considered unrelated to FMT.

    “The other died 13 days post-FMT secondary to progressive pneumonia, for which she was treated with antibiotics before and after FMT. This death was felt to be unrelated to the FMT.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Youngster, 2014, Fecal microbiota transplant for relapsing Clostridium difficle infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study, Clin Infect Dis source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    FMT appears relatively safe in the short term, especially compared with its efficacy in treating recurrent CDI.

    “FMT appears to be relatively safe in the short-term, especially when compared to its efficacy in treating recurrent CDI.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [4] Van Nood, 2013, Duodenal infusion of donor feces for recurrent Clostridium difficile, N Engl J Med source

      Not checked in the free run.

    • cites [27] MacConnachie, 2009, Faecal transplant for recurrent Clostridium difficile-associated diarrhoea: a UK case series, Q J Med

      Not checked in the free run.

    • cites [35] Mattila, 2012, Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection, Gastroenterology source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Microbiota composition changes in IBS are inconsistent across studies, possibly due to heterogeneous populations and differing sample preparation and analysis methods.

    “However, changes in microbiota composition are not consistent across studies, possibly due to heterogeneous study populations and differing methodologies for sample preparation and analysis.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [86] Balsari, 1982, The fecal microbial population in the irritable bowel syndrome, Microbiologica

      Not checked in the free run.

    • cites [87] Malinen, 2005, Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR, Am J Gastroenterol source

      Not checked in the free run.

    • cites [88] Simren, 2013, Intestinal microbiota in functional bowel disorders: a Rome Foundation report, Gut source

      Not checked in the free run.

    • cites [89] Crouzet, 2013, The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota, Neurogastroenterol Motil source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Long-term risks of FMT include possible transmission of infectious agents and development of diseases related to gut microbiota changes.

    “Such risks include the possible transmission of infectious agents via FMT or development of diseases/conditions related to changes in the gut microbiota.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    The influence of administration route on post-FMT symptoms is uncertain.

    “The influence of route of administration on development of symptoms after FMT is uncertain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In those two norovirus cases, donors were asymptomatic and testing for norovirus in one donor was negative.

    “In both cases donors were asymptomatic, and testing for norovirus in one of the donors was negative.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [107] Kahn, 2012, Colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection in a child, Am J Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    FMT is being actively investigated as a therapeutic strategy for metabolic syndrome, type 2 diabetes, fatty liver disease, multidrug-resistant organism eradication, hepatic encephalopathy, and pediatric allergy disorders.

    “FMT is being actively investigated as a therapeutic strategy for many other diseases including the metabolic syndrome, Type 2 diabetes mellitus, fatty liver disease, multidrug resistant organism eradication, hepatic encephalopathy and pediatric allergy disorders.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Those symptoms resolved within 3 hours in all patients and were not reported in the control group receiving only bowel lavage.

    “These symptoms, which resolved in all patients within 3 hours, were not reported in the control group receiving only bowel lavage.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Van Nood, 2013, Duodenal infusion of donor feces for recurrent Clostridium difficile, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Among 16 patients receiving FMT by duodenal infusion plus bowel lavage, 15 had diarrhea, 5 abdominal cramps, 3 belching, and 1 nausea.

    “Among 16 patients receiving FMT via duodenal infusion plus bowel lavage, 15 experienced diarrhea, 5 abdominal cramps, 3 belching, and 1 nausea.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] Van Nood, 2013, Duodenal infusion of donor feces for recurrent Clostridium difficile, N Engl J Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In that study, there were two deaths, one aspiration event related to FMT administration, and 17% of IBD patients had disease flare after FMT.

    “However, there were two deaths, one an aspiration event related to the procedure used to administer FMT and 17% of IBD patients experienced disease flare post-FMT.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Youngster, 2014, Fecal microbiota transplant for relapsing Clostridium difficle infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study, Clin Infect Dis source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These serious procedure-related events include endoscopy complications such as perforation and bleeding, and sedation side effects such as aspiration.

    “These include complications of endoscopy, such as perforation and bleeding, and side effects related to sedation, such as aspiration43.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Youngster, 2014, Fecal microbiota transplant for relapsing Clostridium difficle infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study, Clin Infect Dis source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Little data exists on long-term adverse events of FMT, and many are speculative.

    “Due to the recent emergence FMT, little data exists regarding long-term events and many are speculative.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Production of trimethylamine-N-oxide is dependent on gut microbiota, and higher levels are associated with more major cardiovascular events.

    “production of the pro-atherogenic metabolite trimethylamine-N-oxide is dependent on the gut microbiota, and increased levels of this metabolite are associated with an increase in major cardiovascular events111.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [111] van Nood, 2014, Fecal microbiota transplantation: facts and controversies, Curr Opin Gastroenterol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Patients with recurrent CDI are desperate for a cure and may seek guidance from online communities.

    “Patients suffering from recurrent CDI are desperate for a cure and may seek guidance from online communities.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Patients with recurrent CDI are desperate for a cure and may seek guidance from online communities.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A YouTube video describing do-it-yourself FMT has been viewed over 45,000 times.

    “a YouTube video describing do-it-yourself FMT has been viewed over 45,000 times.112”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [112] Allen-Vercoe, 2012, A Canadian Working Group report on fecal microbial therapy: microbial ecosystems therapeutics, Can J Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Subsequent reports of FMT for children with recurrent CDI without IBD via nasogastric tube, colonoscopy, and capsules show a cure rate of 92% (24/26) and no serious adverse events.

    “others have reported on the safety and efficacy of FMT for children with recurrent CDI without underlying IBD via nasogastric tube, colonoscopy, and capsules with a cure rate of 92% (24/26) and no serious adverse events reported.117, 121–124”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [117] Khanna S, Pardi D, Kelly C, et al. Clinical evaluation of SER-109, a rationally designed, oral microbiome-based therapeutic for the treatment of recurrent Clostridium difficile. 2014.

      Not checked in the free run.

    • cites [121]

      Not checked in the free run.

    • cites [122]

      Not checked in the free run.

    • cites [123]

      Not checked in the free run.

    • cites [124]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Australia's Therapeutic Goods Administration does not consider FMT a drug or regulate it for any indication and has provided no communications regarding FMT.

    “The Therapeutic Goods Administration in Australia, where FMT is not considered a drug or regulated for any indication, has provided no communications regarding FMT.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The IND process is largely tailored to the pharmaceutical industry and regulatory experts.

    “The IND process is largely tailored to the pharmaceutical industry and regulatory experts.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Brandt et al. surveyed 77 patients with recurrent CDI treated with FMT; 97% would want FMT for another recurrence, and 53% would have chosen FMT before antibiotics for first recurrence.

    “Brandt et al surveyed the perceptions of 77 patients who had experienced recurrences of CDI and were treated with FMT; 97% reported that they would want FMT in the event of another recurrence, and 53% of them would have opted for FMT as primary treatment prior to a trial of antibiotics for their first recurrence if given the option.32”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Brandt, 2012, Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection, Am J Gastroenterol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In children with recurrent CDI and underlying IBD, data are mixed, highlighting difficulty distinguishing infection response from underlying disease symptoms.

    “In children with recurrent CDI and underlying IBD, the data the data is mixed, highlighting the difficulty in distinguishing a clinical response to an infection that may have the same symptoms as the underlying disease.118, 121, 124”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [118] Petrof, 2013, Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut, Microbiome source

      Not checked in the free run.

    • cites [121]

      Not checked in the free run.

    • cites [124]

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Without large randomized controlled studies supporting safety and efficacy, FMT is an unapproved product and requires an investigational new drug application to administer.

    “without large randomized controlled studies to support safety and efficacy, it is an unapproved product and an investigational new drug application (IND) is required in order to administer FMT.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [128]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Currently there is no data to support FMT use for childhood food allergies, autism, or chronic diarrhea, and studies are ongoing.

    “currently there is no data to support its use for these conditions and studies are ongoing.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Lack of adequate reimbursement for physician time may further deter FMT use.

    “lack of adequate reimbursement for the time required by physicians may be a further deterrent.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Lack of adequate reimbursement for physician time may deter FMT use.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The FDA maintains that donor eligibility determination and screening, stool processing, and infusion define the FMT product and fall under FDA jurisdiction.

    “the agency has maintained that, at this point, the process of donor eligibility determination and screening, stool processing and infusion defines the FMT “product” and falls under FDA jurisdiction.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [128]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Limited studies report that patients recognize FMT is unappealing but are open to considering it, especially when recommended by a physician.

    “Limited studies on patient perceptions regarding FMT done to date report that patients recognize the unappealing nature of FMT, yet are still open to considering it as a treatment, especially when recommended by a physician.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [113] US Food and Drug Adminstration. FDA drug definition. FDA Glossary of terms. Available at: http://www.fda.gov/drugs/informationondrugs/ucm079436.htm#D. Accessed May 1, 2015.

      Not checked in the free run.

    • cites [114] US Food and Drug Adminstration. Guidance for industry: enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat Clostridium difficile infection not responsive to standard therapies. July 2013. Available at: http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/UCM361393.pdf. Accessed May 1, 2015.

      Not checked in the free run.

    • cites [115] Kelly, 2014, Guidance on preparing an investigational new drug application for fecal microbiota transplantation studies, Clin Gastroenterol Hepatol source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Requiring physicians to hold an IND to administer FMT would prevent many from offering the therapy and ensure only commercial entities with means to navigate regulation and fund large trials control this effective therapy.

    “Requiring physicians to hold an IND to administer FMT would prevent many from offering this therapy and ensure that only commercial entities with the means to navigate the regulatory process and fund large clinical trials will control this effective therapy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    There is significant parental interest in FMT for childhood food allergies, autism, and chronic diarrhea.

    “There has also been significant parental interest in FMT for the treatment of other childhood diseases such as food allergies, autism, and chronic diarrhea”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    That case was a 2-year-old with recalcitrant CDI who failed multiple therapies and had complete symptom resolution within 36 hours of FMT.

    “The case involved a 2 year old child with recalcitrant CDI that had failed an exhaustive course, including probiotics, metronidazole, pulsed-dose vancomycin, rifaximin, and nitazoxanide, who experienced complete resolution of symptoms within 36 hours of FMT.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [118] Petrof, 2013, Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut, Microbiome source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Although several FMT trials are ongoing in China, there is no indication that the Ministry of Health intends to exercise authority over the procedure.

    “Though several FMT trials are ongoing in China, there has been no indication that The Ministry of Health intends to exercise authority over the procedure.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The FDA has determined that administered stool is a biological product and a drug.

    “The United States Food and Drug Administration (FDA) has determined that administered stool constitutes a biological product and a drug”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [128]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Health Canada considers FMT and related synthetic stool therapies a New Biologic Drug and requires clinical studies to go through a clinical trial application to ensure quality and safety standards.

    “Health Canada considers FMT and related synthetic stool therapies as a “New Biologic Drug” and requires any clinical study go through the process of a clinical trial application (CTA) to ensure that quality and safety standards are met.127”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Safety of such products would be monitored by post-market surveillance registries as required by the FDA for biologics and drugs.

    “In turn, the safety of such products would be monitored by post-market surveillance registries as required by the FDA for biologics and drugs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    A priori knowledge is not available about the impact of transferring complex gut microbial communities between individuals, although many mouse studies indicate gut microbiota composition can affect host disease susceptibility.

    “A priori knowledge is not available regarding the impact of transferring these complex communities from one individual to another, although many studies in mice indicate that the composition of the gut microbiota can affect host susceptibility to diseases.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationnone given

    Encapsulated fecal formulations would improve FMT accessibility, simplify clinical trials, and if proven safe could be used earlier in disease.

    “Encapsulated formulations of fecal material would help make FMT accessible to many more patients, simplify clinical trials and, if proven safe, could potentially be used earlier in the course of disease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    National societies have attempted to provide guidance through published guidelines and editorials, but adherence to these recommendations is unknown.

    “national societies have attempted to provide guidance to practitioners through published guidelines and editorials16, 130, 131 but the degree of adherence to these recommendations is unknown.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [16] Bakken, 2011, Treating Clostridium difficile infection with fecal microbiota transplantation, Clin Gastroenterol Hepatol source

      Not checked in the free run.

    • cites [130]

      Not checked in the free run.

    • cites [131]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Other dysbiosis-associated conditions are more complex than CDI, and microbial manipulation for them is unlikely to produce outcomes as dramatic or predictably effective as with CDI.

    “There is speculation that other conditions marked by dysbiosis can be treated with FMT in some form, though these conditions are more complex and the outcomes after microbial manipulation are unlikely to be as dramatic and predictably effective as with CDI.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Other dysbiosis-associated conditions are more complex than CDI.

  • May combine two claims.

    Premisenone given

    Clinical trials of FMT for C. difficile do not fall under enforcement discretion and require an IND.

    “Furthermore, clinical trials of FMT for C. difficile do not fall under enforcement discretion and require an IND.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Frozen preparations of donor material will enable eligible patients to be treated more easily and facilitate clinical research.

    “Frozen preparations of donor material will enable eligible patients to be treated more easily and facilitate clinical research.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Information about FMT effectiveness and short- and long-term safety is not systematically collected, with only case reports available.

    “Information about the effectiveness of FMT as well as both short- and long-term safety data are not systematically collected, with the only available information being case reports published in the literature.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Commercialized preparations of human stool are currently in clinical trials, and the FDA might cease enforcement discretion entirely once one or more products are approved and commercially available.

    “Commercialized preparations of human stool are currently in clinical trials and it is conceivable that the FDA might cease to offer enforcement discretion entirely once one or more of these products is approved and commercially available.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The gut microbiota is a complex consortium with many components that have never been characterized.

    “The gut microbiota is a complex consortium with many components that have never been characterized.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Although the timeline is unknown, a number of commercial products are in late-stage development and may be available within a few years.

    “Although the timeline for the development of these products is currently unknown, a number are in late stage development and may be available within the next few years.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Openbiome is a stool bank located in Medford, MA, USA.

    “Openbiome is a stool bank located in Medford, MA USA.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    In the absence of other therapies, FMT remains the mainstay for management of recurrent CDI not responsive to conventional therapy.

    “In the absence of other therapies FMT remains the mainstay for management of recurrent CDI not responsive to conventional therapy.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    There has been considerable interest in developing a national FMT registry involving collaboration between national professional and advocacy societies.

    “there has been considerable interest in the development of a national FMT registry involving collaboration between national professional and advocacy societies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisereasoning

    The FDA's position on FMT regulation continues to evolve.

    “The position of the FDA on this matter continues to evolve.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The regulatory landscape will continue to evolve as microbiota-based therapeutics emerge.

    “It is clear that the regulatory landscape will continue to evolve as microbiota-based therapeutics emerge.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The regulatory landscape will continue to evolve as microbiota-based therapeutics emerge.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    These products include full-spectrum stool-based products and defined microbial consortia.

    “These include full spectrum stool-based products as well as defined microbial consortia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    They developed a defined microbial community of 33 strains called RePOOPulate based on antibiotic susceptibility, culturability, and community robustness, and administered it to two patients with relapsing C. difficile diarrhea in a proof-of-principle study.

    “They then developed a defined microbial community of 33 strains termed RePOOPulate based on antibiotic susceptibility profiles, culturability and community robustness and administered it to two patients with relapsing C. difficile diarrhea in a proof of principle study.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [133]

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    While FMT's value in treating recurrent CDI is clear, its potential long-term consequences, both beneficial and detrimental, are unknown.

    “While the value of FMT in treating recurrent CDI is clear, its potential long-term detrimental consequences, both beneficial and detrimental, are unknown.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The enforcement discretion policy has enabled many recurrent CDI patients to receive FMT but is probably only temporary.

    “This policy has enabled many patients suffering from recurrent CDI to receive FMT, but is probably only temporary.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Whole-stool FMT as currently practiced is very likely a short-term bridge for CDI treatment that will be replaced by commercially developed products.

    “it is very likely that whole-stool FMT, as currently practiced, is a short-term bridge for the treatment of CDI that will be replaced by commercially developed products.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Whole-stool FMT as currently practiced will be replaced by commercially developed products.

  • May combine two claims.

    Premisecitation

    Under enforcement discretion, the FDA will not enforce the IND requirement as long as providers obtain informed consent, detail procedure risks, and explain FMT is investigational.

    “the FDA will not enforce its own requirement that FMT be done under IND, as long as providers obtain informed consent, detail risks around the procedure, and explain that FMT is considered an investigational therapy.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [129]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Openbiome has supplied over 2000 doses of donor stool to over 200 U.S. institutions at about $250 per dose and has secured an IND for this product.

    “This non-profit organization has already supplied over 2000 doses of donor stool to over 200 institutions in the United States at a cost of around $250 USD per dose and has recently secured an IND for this product.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    Such a registry would serve as a unique national resource of information about clinical practice of FMT in the U.S.

    “Such a registry would serve as a unique national resource of information about the clinical practice of FMT in the U.S.”
    Quote in the paperNot a substantial claim
88 of 88

  • The paper relies on this without support.

    Alterations in gut ecology (dysbiosis) are implicated in multiple disease states, with CDI as the prototypical example.

    “Alterations of this ecology (or dysbiosis) has been implicated in a number of disease states, the prototypical example being Clostridium difficile infection (CDI).”

  • The paper relies on this without support.

    Patients with severe CDI are at greater risk for poor outcomes.

    “Certainly patients with severe CDI are at greater risk for poor outcomes and decisions to proceed with FMT, versus surgery or other standard of care modalities, should be made with caution.”

  • The paper relies on this without support.

    C. difficile generally causes disease in people with decreased diversity of gastrointestinal microflora, typically due to antibiotic use.

    “C. difficile is an opportunistic organism, which generally causes disease in persons with decreased diversity of the gastrointestinal microflora (typically as a result of antibiotic use).”

  • The paper relies on this without support.

    Bile acid composition significantly affects C. difficile growth, with primary bile acids such as taurocholate favoring germination of C. difficile spores.

    “Bile acid composition can significantly impact C. difficile growth with primary bile acids such as taurocholate favoring germination of C. difficile spores.”

  • The paper relies on this without support.

    A lack of effective non-surgical therapies for obesity is a reason to investigate factors that contribute to obesity.

    “The lack of effective, non-surgical therapies has led to investigation of potential factors contributing to the development of obesity.”

  • The paper relies on this without support.

    Gut microbiota can ferment dietary carbohydrates and provide additional energy to the host as short-chain fatty acids.

    “Gut microbiota can ferment dietary carbohydrates and provide additional energy to the host in the form of short chain fatty acids.”

  • The paper relies on this without support.

    Patients with recurrent CDI are desperate for a cure and may seek guidance from online communities.

    “Patients suffering from recurrent CDI are desperate for a cure and may seek guidance from online communities.”

  • The paper relies on this without support.

    Many patients are willing to travel great distances to undergo FMT.

    “Many are willing to travel great distances to undergo FMT.”

  • The paper relies on this without support.

    Some patients perform home enemas of donor stool when they cannot find a willing or able physician to perform FMT.

    “Some have even resorted to performing home-enemas of donor stool when they are unable to find a physician who is willing or able to perform FMT.”

  • The paper relies on this without support.

    Lack of adequate reimbursement for physician time may deter FMT use.

    “lack of adequate reimbursement for the time required by physicians may be a further deterrent.”

  • The paper relies on this without support.

    The regulatory landscape will continue to evolve as microbiota-based therapeutics emerge.

    “It is clear that the regulatory landscape will continue to evolve as microbiota-based therapeutics emerge.”

  • The paper relies on this without support.

    Whole-stool FMT as currently practiced will be replaced by commercially developed products.

    “it is very likely that whole-stool FMT, as currently practiced, is a short-term bridge for the treatment of CDI that will be replaced by commercially developed products.”

  • The paper relies on this without support.

    FMT has high therapeutic efficacy for recurrent CDI.

    “The high therapeutic efficacy of FMT for recurrent CDI is an important proof of concept”

  • The paper relies on this without support.

    Other dysbiosis-associated conditions are more complex than CDI.

    “though these conditions are more complex and the outcomes after microbial manipulation are unlikely to be as dramatic and predictably effective as with CDI”
14 of 14

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Unrelated FMT volunteer donors may be more beneficial in cases where genetics play a contributing factor in the disease, like IBD.

    “Unrelated FMT volunteer donors may be more beneficial in cases where genetics play a contributing factor in the disease, like IBD. 55”

    From Fecal microbiota transplantation: Review and update (2019) · cites this paper as [55]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Route comparison reverses the reported eradication-rate ranges

    Minor

    The text says lower-GI delivery achieved higher eradication rates, but the ranges given in the same sentence are 81-86% for lower-GI delivery and 84-93% for upper-GI delivery. The stated ranges do not support the claimed direction of the comparison.

  • Pediatric case is cited to a paper with a different year

    Minor

    The account dates the Russell pediatric case to 2010 but cites reference 118, which is listed as a 2014 paper. A separate Russell paper from 2010 appears as reference 28.

2 of 2

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Kelly, C. R., Kahn, S., Kashyap, P., Laine, L., Rubin, D., Atreja, A., Moore, T., & Wu, G.
Affiliations
  • Brown University (US)
  • University of Chicago (US)
  • Mayo Clinic (US)
  • Yale University (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • University of Pennsylvania (US)
Corresponding author
Kelly, Colleen R.
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2015-07
Volume
149
Issue
1
Pages
223-237
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2015.05.008
PMC
PMC4755303
OpenAlex
W1756046628
Cited by
572
References
118
Citations by year
2026: 25 · 2025: 29 · 2024: 45 · 2023: 31 · 2022: 44 · 2021: 44 · 2020: 69 · 2019: 74 · 2018: 67 · 2017: 75 · 2016: 56 · 2015: 12
FWCI
10.54
Type
journal article
Language
en
Update notices
erratum (2015-11-01)
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American College of Gastroenterology
  • National Institute of General Medical Sciences (R01GM103591)
  • National Institute of Diabetes and Digestive and Kidney Diseases (K08DK100638, R21DK093839)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
fecal microbiota transplantation, gut microbiota, dysbiosis, Clostridium difficile infection, recurrent Clostridium difficile infection, inflammatory bowel disease, irritable bowel syndrome, metabolic syndrome
MeSH terms
Adult, Biological Therapy, Clostridium Infections, Feces, Female, Humans, Male, Middle Aged, Clostridioides difficile, Microbiota

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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