Therapeutic Potential of Fecal Microbiota Therapy (FMT)

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 17105

Special Issue Editor

Special Issue Information

Dear Colleagues,

Fecal microbiota therapy (FMT) represents a new therapeutic approach that involves the application of a solution of fecal material from a healthy donor into the gut of the receiver with the intention of restoring gut dysbiosis. The therapeutic potential of FMT has been explored in the treatment of a multitude of diseases, both gastrointestinal and extraintestinal. The route to delivering FMT may be very different (upper vs. lower GI tract) in dependence of the disease that we are treating with FMT. From a clinical point of view, FMT has been shown to be a very effective method in the treatment of recurrent C. difficile infection that represents the most common hospital-acquired infection. FMT is currently tested as a therapeutic option for multiple diseases beyond Clostridium difficile. An important area of interest for FMT is the treatment of inflammatory bowel disease (IBD). Recently, the first randomized controlled trials exploring the use of FMT for treatment of IBD were published. The results are promising, but many questions remain unanswered in terms of donor selection, preparation of FMT, and route of treatment (foregut, hindgut, or a combination). FMT appears to be a promising option to treat functional gastrointestinal disorders, especially irritable bowel syndrome (IBS). However, the results of randomized studies show contradictory results. Preliminary studies indicate a possible potential of FMT to treat chronic liver diseases such as alcoholic and non-alcoholic steatohepatitis (ASH, NASH), complication of liver cirrhosis or primary sclerosing cholangitis (PSC). Further possible indications include neuropsychiatric diseases, autoimmune diseases, obesity, metabolic syndrome, and other dysbiosis-associated diseases. The main limiting factors for the expansion of this method are the potential risk of infections or transfer of propensity for the development of chronic diseases by an unknown microbial agent. In summary, the restoration of gut microbiota by FMT holds promise that this method may be effective in the treatment of infectious, inflammatory, and functional disorders of gastrointestinal tract and non-gastrointestinal diseases.

On these grounds, in this Special Issue, we welcome research articles, case reposts, and short communications to present the recent advances in the fecal microbiota therapy.

Prof. Dr. Peter C. Konturek
Guest Editor

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Keywords

  • fecal microbiota therapy
  • gut microbiota
  • Clostridium difficile infection
  • inflammatory bowel disease
  • gastrointestinal disorders
  • irritable bowel syndrome
  • gastrointestinal diseases

Published Papers (5 papers)

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Research

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13 pages, 755 KiB  
Article
Ten-Year Follow-Up of Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection from a Randomized Controlled Trial and Review of the Literature
Microorganisms 2021, 9(3), 548; https://doi.org/10.3390/microorganisms9030548 - 06 Mar 2021
Cited by 10 | Viewed by 2036
Abstract
Fecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT have been well documented, there still is a paucity of data with regard to long-term safety. In this report, [...] Read more.
Fecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT have been well documented, there still is a paucity of data with regard to long-term safety. In this report, we describe the long-term follow-up of the prospective cohort of the first randomized controlled trial of FMT for rCDI, and review the existing literature. A total of 34 patients were treated with FMT for rCDI. Seven patients were still alive after a follow-up of more than 10 years and three patients were lost to follow-up. None of the 34 patients had experienced a new-onset autoimmune, gastrointestinal, or malignant disorder during follow-up. We did not find any deterioration or amelioration of pre-existing medical conditions. Furthermore, no deaths directly attributable to FMT could be identified. These findings are in accordance with the data in available literature. In conclusion, no long-term adverse events or complications directly attributable to FMT were found in our prospective cohort. Review of the available literature does not point to long-term risks associated with FMT in this elderly population, provided that carefully screened fecal suspensions are being used. No firm conclusion on the long-term safety of FMT in younger patients could be drawn. Full article
(This article belongs to the Special Issue Therapeutic Potential of Fecal Microbiota Therapy (FMT))
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24 pages, 3878 KiB  
Article
An Oral FMT Capsule as Efficient as an Enema for Microbiota Reconstruction Following Disruption by Antibiotics, as Assessed in an In Vitro Human Gut Model
Microorganisms 2021, 9(2), 358; https://doi.org/10.3390/microorganisms9020358 - 11 Feb 2021
Cited by 11 | Viewed by 4832
Abstract
Fecal microbiota transplantation (FMT) is an innovative therapy already used in humans to treat Clostridioides difficile infections associated with massive use of antibiotics. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics, and cost constraints. [...] Read more.
Fecal microbiota transplantation (FMT) is an innovative therapy already used in humans to treat Clostridioides difficile infections associated with massive use of antibiotics. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics, and cost constraints. In the present study, an in vitro model of the human colon reproducing medically relevant perturbation of the colonic ecosystem by antibiotherapy was used to compare the efficiency of traditional FMT enema formulations and a new oral capsule in restoring gut microbiota composition and activity. Loss of microbial diversity, shift in bacterial populations, and sharp decrease in fermentation activities induced in vivo by antibiotherapy were efficiently reproduced in the in vitro model, while capturing inter-individual variability of gut microbiome. Oral capsule was as efficient as enema to decrease the number of disturbed days and bacterial load had no effect on enema performance. This study shows the relevance of human colon models as an alternative approach to in vivo assays during preclinical studies for evaluating FMT efficiency. The potential of this in vitro approach could be extended to FMT testing in the management of many digestive or extra-intestinal pathologies where gut microbial dysbiosis has been evidenced such as inflammatory bowel diseases, obesity or cancers. Full article
(This article belongs to the Special Issue Therapeutic Potential of Fecal Microbiota Therapy (FMT))
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15 pages, 4022 KiB  
Article
Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial
Microorganisms 2020, 8(6), 941; https://doi.org/10.3390/microorganisms8060941 - 23 Jun 2020
Cited by 20 | Viewed by 3232
Abstract
Background: The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics [...] Read more.
Background: The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. Methods: We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). Results: Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). Bifidobacterium species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. Conclusions: Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE. Full article
(This article belongs to the Special Issue Therapeutic Potential of Fecal Microbiota Therapy (FMT))
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Review

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17 pages, 753 KiB  
Review
Fecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Systematic Review
Microorganisms 2020, 8(9), 1433; https://doi.org/10.3390/microorganisms8091433 - 18 Sep 2020
Cited by 15 | Viewed by 2320
Abstract
The objective was to evaluate available literature on treatment of chronic pouchitis with fecal microbiota transplantation (FMT) focusing on clinical outcomes, safety, and different approaches to FMT preparation and delivery. A systematic review of electronic databases was conducted using Medline, EMBASE, and the [...] Read more.
The objective was to evaluate available literature on treatment of chronic pouchitis with fecal microbiota transplantation (FMT) focusing on clinical outcomes, safety, and different approaches to FMT preparation and delivery. A systematic review of electronic databases was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials Library from inception through April 2020. Human studies of all study types reporting results of FMT to treat chronic pouchitis were included. Nine studies, reporting FMT treatment of 69 patients with chronic pouchitis were found eligible for the review. Most studies were case series and cohort studies rated as having fair to poor quality due to high risk of bias and small sample size. Only one randomized controlled trial was included, finding no beneficial effect of FMT. In total clinical response after FMT was reported in 14 (31.8%) out of 44 evaluated patients at various timepoints after FMT, and clinical remission in ten (22.7%) patients. Only minor self-limiting adverse events were reported. FMT varied greatly regarding preparation, length of treatment, and route of delivery. The effects of FMT on symptoms of chronic pouchitis are not established, though some studies show promising results. Future controlled well-designed studies are warranted. Full article
(This article belongs to the Special Issue Therapeutic Potential of Fecal Microbiota Therapy (FMT))
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Other

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12 pages, 1741 KiB  
Brief Report
Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations
Microorganisms 2020, 8(10), 1486; https://doi.org/10.3390/microorganisms8101486 - 27 Sep 2020
Cited by 17 | Viewed by 3928
Abstract
Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- [...] Read more.
Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status. Full article
(This article belongs to the Special Issue Therapeutic Potential of Fecal Microbiota Therapy (FMT))
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