Low Resolution rates in Open-Label and Randomized Controlled Trials of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-Analysis

Tariq, Raseen; Pardi, Darrell S.; Bartlett, Mark; Khanna, Sahil

doi:10.14309/00000434-201710001-00102

Cited by 31 publications

(50 citation statements)

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“…Case series or individual case reports have supported efficacy estimates up to 93%, but small uncontrolled trials are prone to bias [18]. Notably, a 2019 metaanalysis found that FMT was associated with lower cure rates in randomized trials (67.7%) compared with open-label studies (82.7%; P < .001) [19].…”

Section: What Is the Quality Of Data Supporting Fmt Efficacy In Reducmentioning

confidence: 99%

The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis

Wilcox

McGovern

Hecht

2020

Open Forum Infectious Diseases

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The leading risk factor for Clostridioides (Clostridium) difficile infection (CDI) is broad-spectrum antibiotics, which lead to low microbial diversity, or dysbiosis. Current therapeutic strategies for CDI are insufficient, as they do not address the key role of the microbiome in preventing C. difficile spore germination into toxin-producing vegetative bacteria, which leads to symptomatic disease. Fecal microbiota transplant (FMT) appears to reduce the risk of recurrent CDI through microbiome restoration. However, a wide range of efficacy rates have been reported, and few placebo-controlled trials have been conducted, limiting our understanding of FMT efficacy and safety. We discuss the current knowledge gaps driven by questions around the quality and consistency of clinical trial results, patient selection, diagnostic methodologies, use of suppressive antibiotic therapy, and methods for adverse event reporting. We provide specific recommendations for future trial designs of FMT to provide improved quality of the clinical evidence to better inform treatment guidelines.

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Section: What Is the Quality Of Data Supporting Fmt Efficacy In Reducmentioning

confidence: 99%

The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis

Wilcox

McGovern

Hecht

2020

Open Forum Infectious Diseases

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“…Since faecal transplantation of 'healthy stool' to patients with recurrent Clostridium difficile infections has been established as a therapy (60) , the principle of transferring microbiomes has also been applied to study metabolic health effects.…”

Section: Microbiome and Metabolic Healthmentioning

confidence: 99%

Diet and the gut microbiome: from hype to hypothesis

Daniel

2020

Br J Nutr

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Abstract Microbiome research in the last two decades has delivered as a key finding that the human intestine hosts a unique and complex ecosystem with many variables affecting the composition of the microbiota and in turn its function in metabolism and immune defence. Hundreds of external (environmental) factors have meanwhile been identified as significantly associated with bacterial biomass and diversity and, amongst these, diet is considered as a key determinant of microbial populations. However, dietary intervention studies, including those with fermentable substrates that have bulk effects on bowel functions, have revealed only very minor effects on overall microbiome composition and usually show only a very few species changing in population size. What that means in the context of hundreds of different species coexisting in competition or mutualism in the human colon is far from understood. This review addresses some of the current limits in research on diet effects by taking anatomical and physiological features of the intestine into consideration. It also provides some recommendations on future human studies needed to assess how the diet influences the microbiome and associated effects on metabolic health.

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“…It would certainly be desirable that future microbiome–disease association studies conduct power calculations with realistically anticipated effect sizes in their published results, as routinely done in the protocols for clinical trials. Such approaches plus meta‐analyses will help to distinguish true from spurious associations to allow focusing on promising microbiota–disease associations that lead the field from hype to hope (McKenney & Pamer ), with meta‐analyses of faecal transfer in C. difficile infection serving as an example (Tariq et al ., ).…”

Section: Introductionmentioning

confidence: 97%

“…One notable exception is faecal transplantation for the treatment of recurrent Clostridium difficile infections (CDI). However, despite clear data on its efficacy (Tariq et al ., ), its development into a commercial product meets regulatory hurdles (Vyas et al ., ; Verbeke et al ., ), and the FDA has recently issued a safety alert pertaining to its use (https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-safety-alert-regarding-use-fecal-microbiota-transplantation-and-risk-serious-adverse). Furthermore, the basic concept of this approach predates microbiome research (de Vos, ), and defined bacterial strains for recurrent CDI (Tvede and Rask‐Madsen, ; Tvede et al ., ) still need to be developed into registered products.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical intervention trials are finally the critical test for the practical value of microbiome research. The success of faecal transplantation in C. difficile infection is a sign of hope (Tariq et al ., ), but we need to decipher how it works mechanistically, both to achieve an industrial product and to understand why faecal transplantation works less well in other gastroenterology diseases (Imdad et al ., ).…”

Section: Introductionmentioning

confidence: 99%

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Problems with the concept of gut microbiota dysbiosis

Brüssow

2019

Microbial Biotechnology

173

137

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Summary The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning ‘dysbiosis’ that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case–control studies are underpowered necessitating more meta‐analyses that sort out consistent from spurious dysbiosis–disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe–microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.

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Low Resolution rates in Open-Label and Randomized Controlled Trials of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-Analysis

Cited by 31 publications

References 0 publications

The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis

The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis

Diet and the gut microbiome: from hype to hypothesis

Problems with the concept of gut microbiota dysbiosis

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