Mechanisms underpinning the efficacy of faecal microbiota transplantation in treating gastrointestinal disease

Segal, Jonathan; Mullish, Benjamin H.; Quraishi, Mohammed Nabil; Iqbal, Tariq; Marchesi, Julian R.; Sokol, Harry

doi:10.1177/1756284820946904

Cited by 26 publications

(26 citation statements)

References 113 publications

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“…Potential factors could be the bacteriophages (Caudovirales) or the metabonomics, especially short-chain fatty acids (SCFAs) (Segal et al, 2020). A study showed a higher success rate of FMT with donor samples containing higher fraction of Caudovirales within the stool virome, and after FMT the abundance of the order of Caudovirales bacteriophages reduced significantly in the recipient's stool (Zuo et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

How to Apply FMT More Effectively, Conveniently and Flexible – A Comparison of FMT Methods

Varga

Kocsis

Sipos

et al. 2021

Front. Cell. Infect. Microbiol.

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PurposeMetronidazol and vancomycin were long the two best options against Clostridioides (formerly Clostridium) difficile infections (CDI). Now, the cost of new drugs such as fidaxomicin directs us towards alternative treatment options, such as faecal microbiota transplant (FMT). Its effectiveness is similar to fidaxomicin. There are questions regarding its safety, but the biggest challenges are prejudice and inconvenience. Most protocols refer to FMT applied in the form of a solution. We investigated different modalities of FMT.MethodsInstead of using nasoenteric tubes or colonoscopy, we place frozen or lyophilised stool in non-coated, size “00”, hard gelatine capsules or enterosolvent, size “0” capsules.ResultsWe found that non-coated, size “00”, hard gelatine capsules are appropriate for conducting FMT. Capsules containing lyophilised supernatant with a low number of bacteria have been proven to be non-inferior to other FMT modalities. The primary cure rate in the supernatant group was 93.75%, and 66.67% in the sediment group. The overall cure rate was 82.14%. Depending on the protocol, 4–7 capsules are sufficient per patient. Capsules can be stored for up to one year at -20°C.ConclusionsFMT is a feasible alternative to antibiotic treatments in CDI. Our method makes the process flexible and less inconvenient to patients. Long storage time allows a consistent supply of capsules, while small volume and formulation make the procedure tolerable.

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Section: Discussionmentioning

confidence: 99%

How to Apply FMT More Effectively, Conveniently and Flexible – A Comparison of FMT Methods

Varga

Kocsis

Sipos

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Intervention aiming to ameliorate this pathological environment with the delivery of targeted beneficial or wholesale bacterial populations in the form of probiotics and faecal microbiota transplantation (FMT), respectively, has been in clinical practice for many years (233,234). The various mechanisms by which probiotics and FMT exert their therapeutic effect has been reviewed in detail elsewhere (235)(236)(237), but centre on their interaction with the host mucosal immune system via MAMPs (238,239) or extracellular vesicles (240)(241)(242), the surrounding microbiota via AMPs (243), Downloaded from http://portlandpress.com/bioscirep/article-pdf/doi/10.1042/BSR20203850/913272/bsr-2020-3850c.pdf by guest on 07 June 2021 microbial cross-feeding (244) or nutrient competition, and their contribution to the broader mucosal metabolic environment (118,148). Here we review the latest developments and innovations in probiotics and FMT.…”

Section: Microbiota-targeted Therapiesmentioning

confidence: 99%

The role of the microbiome in gastrointestinal inflammation

et al. 2021

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The microbiome plays an important role in maintaining human health. Despite multiple factors being attributed to the shaping of the human microbiome, extrinsic factors such diet and use of medications including antibiotics appear to dominate. Mucosal surfaces, particularly in the gut, are highly adapted to be able to tolerate a large population of microorganisms while still being able to produce a rapid and effective immune response against infection. The intestinal microbiome is not functionally independent from the host mucosa and can, through presentation of microbe-associated molecular patterns and generation of microbial-derived metabolites, fundamentally influence mucosal barrier integrity and modulate host immunity. In a healthy gut there is an abundance of beneficial bacteria that help to preserve intestinal homeostasis, promote protective immune responses and limit excessive inflammation. The importance of the microbiome is further highlighted during dysbiosis where a loss of this finely-balanced microbial population can lead to mucosal barrier dysfunction, aberrant immune responses, and chronic inflammation that increases the risk of disease development. Improvements in our understanding of the microbiome are providing opportunities to harness members of a healthy microbiome to help reverse dysbiosis, reduced inflammation and ultimately prevent disease progression.

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“…The role that FMT plays in restoring colonization resistance via commensal bacteria outcompeting pathobionts for critical nutrients, alteration of pH or oxygen tension, and production of metabolites toxic to them is an another potential contributory mechanism of benefit (Kamada et al, 2013). Supporting this concept, FMT is recognized to restore gut microbial metabolites that are key to gut barrier function (including short chain fatty acids and bile acids) from the low levels found in an antibiotic-exposed gut back to higher levels comparable to healthy stool donors (McDonald et al, 2018;Monaghan et al, 2019;Mullish et al, 2019;Martinez-Gili et al, 2020;Segal et al, 2020). This restoration of gut barrier integrity may limit translocation of pathobionts from the intestinal lumen into the circulation, and therefore reduce the risk of bacteremia.…”

Section: Discussionmentioning

confidence: 99%

“…In mouse models, FMT has been seen to reverse the course of otherwise lethal human bacterial mediated sepsis by enhancing pathobiont clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner (Kim et al, 2020). As such, part of the benefit of FMT in this setting may involve gut commensal-mediated immune priming, without necessarily significantly suppressing MDRO that colonize the gut (Allegretti et al, 2019;Woodworth et al, 2019;Segal et al, 2020;Bar-Yoseph et al, 2021;Huus et al, 2021). The role that FMT plays in restoring colonization resistance via commensal bacteria outcompeting pathobionts for critical nutrients, alteration of pH or oxygen tension, and production of metabolites toxic to them is an another potential contributory mechanism of benefit (Kamada et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation

Innes

Mullish

Ghani

et al. 2021

Front. Cell. Infect. Microbiol.

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The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2% respectively, p=0.24) between the FMT-MDRO group and their paired non-MDRO cohort. Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by pre-HCT FMT, even in the absence of intestinal MDRO decolonization. Further work is needed to explore this observed benefit.

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Mechanisms underpinning the efficacy of faecal microbiota transplantation in treating gastrointestinal disease

Cited by 26 publications

References 113 publications

How to Apply FMT More Effectively, Conveniently and Flexible – A Comparison of FMT Methods

How to Apply FMT More Effectively, Conveniently and Flexible – A Comparison of FMT Methods

The role of the microbiome in gastrointestinal inflammation

Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation

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