Hot Topic Review

Fecal Microbiota Transplantation for Ulcerative

Colitis: An Evolving Therapy

Ajit Sood, MD,* Arshdeep Singh, MD, DM,*, Vandana Midha, MD,† Ramit Mahajan, MD,
DM,*, Dina Kao, MD,‡ David T. Rubin, MD,§, and Charles N. Bernstein, MD¶,

Background: Fecal microbiota transplantation (FMT) is currently an approved treatment for recurrent and refractory Clostridioides difficile
infection. However, its use in ulcerative colitis is at an early stage and significant gaps remain in our understanding of the mechanisms and logis-
tics of its practical application.
Methods and results: This article aims to look into specific issues which remain unsettled for use of FMT in ulcerative colitis including donor
and recipient selection, route of administration, and duration of therapy. We also discuss optimal ways to assess response to FMT and the current
state of FMT regulations. In addition, we postulate the impact of diet on the microbiome profile of the donor and recipient. We also suggest a
change in the nomenclature from FMT to fecal microbiome transfer.
Conclusion: FMT is an evolving therapy. There are several considerations for its use in UC but its use and role should be directed by further
clinical trials.

Lay Summary
This article explores fecal microbiota transplantation (FMT) in the treatment of ulcerative colitis in regards to donor and recipient selection, ad-
ministration route, therapy duration, and donor diet. We discuss assessment of FMT response and the current state of FMT regulation.
Key Words: fecal microbiome transfer, fecal microbial transplantation, ulcerative colitis, randomized controlled trial

INTRODUCTION FMT was used for UC in 1989 by Bennet and Borody.3,4

Fecal microbiota transplantation (FMT) is defined as However, interest in FMT for inflammatory bowel disease
the administration of healthy donor whole stool (that consists (IBD) was heightened after 2 randomized trials evaluating
of microbial communities and their functional ecologies) FMT for induction of remission in UC were published with
into the gastrointestinal (GI) tract of an individual with conflicting results in the year 2015.5,6 Since then there have
the aim of correcting dysbiosis. It is currently the approved been 2 more randomized controlled trials (RCTs, both from
treatment for recurrent/refractory Clostridioides difficile Australia) demonstrating efficacy of FMT in inducing remis-
infection (rCDI).1,2 However, the use of FMT in ulcerative sion in UC.7,8 Benefit with multisession colonoscopic FMT
colitis (UC) is still evolving with many issued remaining in inducing remission in patients with steroid-dependent UC
unsettled. has also been reported.9 Though the literature suggests that
Inc., Genentech/Roche, Janssen Pharmaceuticals, Lilly, Mahana Therapeutics,
Received for publications June 11, 2020; Editorial Decision July 18, 2020. Medtronic, Merck & Co., Inc., Napo Pharmaceuticals, Pfizer, Prometheus
*Department of Gastroenterology, Dayanand Medical College and Hospital, Laboratories, Shire, Takeda, and Target PharmaSolutions, Inc. Ajit Sood,
Ludhiana, India; †Department of Internal Medicine, Dayanand Medical College Arshdeep Singh, Vandana Midha, Ramit Mahajan, and Dina Kao have no con-
and Hospital, Ludhiana, India; ‡Division of Gastroenterology, Department of flicts of interest to declare.
Medicine, University of Alberta, Edmonton, Alberta, Canada; §Inflammatory Author Contribution: Conceived on concept and wrote initial draft of man-
Bowel Disease Center, Department of Medicine, University of Chicago, Chicago, uscript (A.S., Ar.S., V.M., R.M.). Reviewed and approved final manuscript (A.S.,
Illinois, USA; ¶University of Manitoba IBD Clinical and Research Centre and Ar.S., V.M., R.M., D.K., D.R., C.N.B.).
Section of Gastroenterology, Department of Medicine, Max Rady College of
Address correspondence to: Charles N. Bernstein, MD, University of
Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg,
Manitoba, 804-715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
Manitoba, Canada
(Charles.bernstein@umanitoba.ca).
Funding: None.
© The Author(s) 2020. Published by Oxford University Press on behalf of
Potential Conflicts of Interest: Dr Bernstein has served on advisory boards or Crohn’s & Colitis Foundation.
consulted to Abbvie Canada, Ferring Canada, Janssen Canada, Pfizer Canada,
Shire Canada, Takeda Canada, Mylan Pharmaceuticals, and has received unre- This is an Open Access article distributed under the terms of the Creative
stricted educational grants from Abbvie Canada, Janssen Canada, Pfizer Canada, Commons Attribution Non-Commercial License (http://creativecommons.
Shire Canada, and Takeda Canada. He has been on the speaker’s bureau for org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution,
Takeda Canada, Abbvie Canada, Janssen Canada, and Medtronic Canada. and ­reproduction in any medium, provided the original work is properly cited.
David T. Rubin has received research funding from Takeda, and has served as For ­commercial re-use, please contact journals.permissions@oup.com
a consultant to Abbvie, Abgenomics, Allergan, Inc., Arena Pharmaceuticals, doi: 10.1093/crocol/otaa067
Biomica, Bristol-Myers Squibb, Dizal Pharmaceuticals, Ferring Pharmaceuticals, Published online 15 August 2020

Crohn’s & Colitis 360 • Volume 2, Number 4, October 2020 1


Sood et al Crohn’s & Colitis 360 • Volume 2, Number 4, October 2020

FMT increases the proportion of participants achieving clin- diversity within Firmicutes and an increased proportion of
ical remission in UC, no firm conclusions can be drawn at the Proteobacteria.13 FMT is expected to correct this dysbiosis and
moment.10 However, it has been consistently shown that re- thereby reduce gut inflammation in UC. However, to date, no
sponders to FMT experience microbial enrichment (increase in specific group of microbes have been established in relation to
microbiota diversity) and a shift in composition that resembles response to FMT in UC. Fuentes et al reported that an increase
the profile of their donor, similar to what has been found in in Anaerostipes caccae, Coprococcus eutactus, or Eubacterium
rCDI patients. rectale and decrease in Enterococcus species were associated
A comprehensive literature search was carried out on with good clinical response while persistence of Proteobacteria
MEDLINE, MedIndia, EMBASE, and Cochrane Central and Bacteroidetes and low levels of Clostridium clusters IV and
Register of Controlled Trials for relevant literature published XIVa were associated with treatment failure.14 Butyrate pro-
on use of FMT in UC. All the original articles, systematic re- ducing Eubacterium hallii, Roseburia inulinivorans, Eggerthella
views, meta-analyses, conference abstracts, and review articles species, and Ruminococcus bromii also correlated with re-
were included. Medical Subject Headings (MeSH) terms used sponse to FMT whereas Fusobacteria, Escherichia, Sutterella,
to coin search strategies were “faecal microbiota transplant” Streptococcus, and Prevotella were associated with lack of remis-
“fecal microbiome transplant” “fecal microflora transplant” sion in another RCT.15 However, Costello et al identified a dif-
“fecal bacteriotherapy” “stool transplant” “fecal transfu- ferent set of microbes (Anaerofilum pentosovorans, Bacteroides
sion” “donor feces infusion,” “fecal transplant,” “fecal trans- coprophilus, Clostridium methylpentosum, Acidaminococcus
plantation,” “fecal microbiota transplantation,” “intestinal intestine, and Senegalimassilia anaerobia) in association with
microbiota transfer,” “ulcerative colitis,” “colitis gravis,” “in- response to FMT. Interestingly, fecal short chain fatty acid
flammatory bowel disease,” “IBD,” and “bowel diseases, in- concentrations, including butyrate, did not correlate with any
flammatory.” The methodologies in published trials on FMT observed treatment effect with FMT.7
in UC are heterogeneous. The available literature lacks uni- The microorganisms within the intestinal tract not only
formity on practical application of FMT especially with regard synergistically cooperate in nutrient digestion and metabolism
to patient and donor selection, dose, route, and frequency, and but also intensely compete with each other for nutrients and
long-term follow-up policy. This review discusses the informa- space. The exclusion of competitive niche by FMT-induced res-
tion and gaps in our understanding of the mechanisms of toration of microbial communities (and thereby preventing op-
FMT pertaining to its application in UC. portunistic pathogens to persist and proliferate) is one of the
plausible mechanisms for its therapeutic effect.16–18
HOW DOES FMT WORK IN UC The mucosal immune system is characterized by its ex-
Gut microbiome within an individual is variable and clusivity. Commensal microorganisms play an important role
dynamic and therefore defining a “normal” healthy gut in development as well as maturation of the mucosal immu-
microbiome is not possible at the moment. The gut-microbial nity. Several immune mechanisms that work in tandem with
health is characterized by 3 parameters: (1) resistance to dis- the microbiota to establish and maintain gut homeostasis are
turbances in the intestinal ecologies, (2) resilience to revert back dysregulated in patients with IBD.19–23 FMT attempts to re-
to original composition even if disturbed, and (3) functional re- store the equilibrium by correcting microbial dysbiosis. Animal
dundancy if there is delay in regaining the predisturbance com- models have shown reduced colonic inflammation following
position so that compositional shifts do not affect the functions FMT due to reestablishment of colonic CD4+ and Treg cells,
of ecological niches. The gut-microbial health therefore hangs increase in interleukin-10 (IL-10) production, reduced ability
in a delicate balance with the potential to be influenced by a of antigen presenting cells to present bacterial antigens to the
large number of environmental factors. If the effects induced colonic T cells, and restoration of intestinal memory/effector
by external factors exceed the ability of microbial community T cell populations.24–26 The only clinical trial assessing the im-
to resist the change, resulting dysbiosis can affect the function- munological changes with FMT failed to demonstrate any
ality of the intestinal microenvironment culminating in unfa- significant changes in mucosal T cell subsets.7 The current un-
vorable consequences.11,12 derstanding of immunoregulatory changes with FMT is limited
Whether the immune-mediated damage in IBD is due to and well-designed focused studies with adequate sample sizes
recognition of particular bacterial epitopes or due to molec- are needed.
ular mimicry-mediated autoimmune reactions is still obscure.
Further, whether dysbiosis is a cause (that sets the inflamma- UNSETTLED ISSUES REGARDING FMT FOR UC
tory process in motion) or an effect (of altered immune and
metabolic environment of the inflamed mucosa) is unclear Patient Selection
and it complicates the feasibility of an in-depth analysis of The majority of the participants in the random-
changes brought by FMT in patients with IBD. Dysbiosis in ized trials published so far have been middle-aged with
IBD is characterized by reduction in Bacteroidetes, reduced mild-to-moderately active UC who were on stable doses of

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Crohn’s & Colitis 360 • Volume 2, Number 4, October 2020 Intestinal Microbiome Transfer in UC

concomitant medications.5–8 As these RCTs are heteroge- same donor, the so-called “super donor.” Microbial diversity
neous with regard to the route and dose of administration, of the donor stool was the most important predictor of FMT
number of treatment sessions, choice of placebo, and the outcome.30 If this hypothesis was true, multidonor FMT infu-
exact indication for FMT, the results cannot be compared. sions to ensure greater microbial diversity than from individual
The lower response rates observed with severe disease in donors should result in a higher response rate.8 Despite using
these trials suggest that severe disease is less likely to re- multidonor intensive FMT, Paramsothy et al did not signif-
spond.5,6 While no significant interaction between age, sex, icantly increase the response rate (27% vs 24% in Moayyedi
disease duration and distribution, and concomitant medica- et al).5,8 Therefore, “one stool fits all” approach may not hold
tions was observed in the post hoc analysis of RCTs,5,7 the true in the context of treating microbial dysbiosis-associated
authors in India found younger age, disease extent E2 and chronic diseases. Detailed characterization of donors and
endoscopic Mayo subscore 2 to be associated with achieve- recipients with a multiomics approach (metagenomics,
ment of clinical remission (unpublished work). metatranscriptomics, and metabolomics) in an attempt to cor-
As is evident from RCTs and cohort studies, none of rect functional deficiencies through appropriate matching may
the studies used FMT as the only therapeutic agent or as potentially improve efficacy.31
initial therapy. Patients not responding to standard phar-
macotherapy including corticosteroids, 5-aminosalicylates Preparation of the Fecal Slurry
(5-ASA), thiopurines, and/or biologics were subjected to The process of preparation of the fecal slurry has evolved
FMT. In the first focused open label uncontrolled study from using a blender to a more refined centrifugation plus fil-
evaluating role of FMT in a selective group of steroid- tration (using automated blenders) and centrifugation plus
dependent patients with moderately severe UC, high rates microfiltration (using automated purification system based on
of clinical response (75%) and steroid-free clinical remission GenFMTer).32 The refined techniques minimize manual hand-
(46%) were documented.9 With limited use of antibodies to ling of the fecal sample, prevent contamination, and result in
tumor necrosis factor (anti-TNF) biologics in developing uniform homogenization of the slurry. The experience with
countries due to high cost and prevalence of tuberculosis, laminar flow cabinet or tissue culture hood with UV-C germi-
FMT potentially presents itself as a salvage therapy in such cidal lamp during preparation of slurry is limited.
patients. This observation however needs further corrobora- There is evidence that the proportion of viable bacteria re-
tion in large randomized trials. duces when donor stool sample is processed in ambient air com-
pared to anaerobic processing.33 However, trials comparing aerobic
Donor Selection and anaerobic preparations are lacking at this moment in time.
The objective of donor selection through stringent The impact of storing and freezing donor stool on the microbial
screening is to prevent any adverse event related to the infused viability and therapeutic efficacy remains unknown. Costello et al
fecal material. Donor screening is usually conducted in accord- reported that the microbiome remained largely unchanged after
ance with local regulatory authorities or governing bodies. The 6 months of storage.34 On the contrary there are reports of declining
first step in selecting the potential donor is a detailed medical microbial viability when stool is stored for more than 8 hours.35 The
history and risk behavior assessment by use of a dedicated ideal situation would be to deliver the fecal slurry into the recipient
questionnaire. Once a potential donor has been found suit- bowel as early as possible in its purest form, free of preservatives. By
able based on the donor questionnaire, he/she is subjected to a incorporating this time control for preparation, higher rates of clin-
structured physical and laboratory evaluation.27–29 Interactions ical response can be expected.32 However, this may be challenging
between the donor screening staff and donors need to be sched- because of logistic difficulties and restrictions.
uled on a regular basis (preferably every 1–2 months) to identify
problems related to donation. Route of Administration
Apart from screening for infectious agents and multidrug- There is no consensus on the most appropriate route of
resistant organisms, profiling microbial diversity and function- administration of FMT. The RCTs with a colonic or rectal in-
ality holds the key to optimal donor selection. The genetic stillation of fecal slurry5,7,8 have shown better response rates
background and dietary intake of both recipients and donors compared to the upper GI route of administration.6 In a meta-
(which affects the gut microbiome) is not routinely analyzed analysis based on cohort studies, the pooled proportion of
currently but may become part of the standard workup in clinical remission rates with upper and lower GI tract adminis-
the future. tration of fecal slurry were 8% and 31%, respectively.36 Gastric
Moayyedi et al observed varied response to different acid can impairing the growth and survival of Bacteroides and
stool donors. Taxonomic profiles of the donors highlighted Firmicutes may be responsible for lower response rates with
distinct microbial differences between the 2 donors. Of the 9 upper GI delivery.37 However, this may be negated by using
patients who entered remission, 7 had received FMT from the proton pump inhibitors or delivering the fecal slurry into

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Sood et al Crohn’s & Colitis 360 • Volume 2, Number 4, October 2020

duodenum or jejunum. The response rates when fecal slurry is to be feasible in North America and Europe. The development
delivered by enema varies from 24% to 32% in RCTs.5,7,8 In com- of purified capsular forms of select intestinal microbiome com-
parison when multisession colonoscopic approach was used, ponents may provide a more efficient and less expensive method
steroid-free clinical remission was achieved in 46.3% of pa- of maintenance.
tients.9 A small open label pilot study has demonstrated the ef-
ficacy of capsule-based long-term multidonor FMT. However, Impact of Diet on Response to FMT
the number of participants was small and 20% developed se- Diet is one of the most important determinants of
rious adverse effects and dropped out.38 Further studies with gut-microbial composition.44–46 It has been proposed that the
head to head comparisons of the oral and colonoscopic route habitual diet consumed over the long term decides the funda-
are needed to determine the optimal approach. mental microbial health.12 Complex interactions between die-
tary nutrients and microbiota shape the immune responses
Need for Maintenance Therapy that trigger/sustain the disease. Maintaining a healthy diet is
Because of complex and persistent pathologic mechan- hence important for both the donor and the recipient of FMT.
isms in UC, therapeutic microbial manipulation with a single A donor who is screened and selected today may not be ac-
session of FMT is unlikely to have sustained benefits.39 In one ceptable tomorrow if there are significant deviations in die-
study the median time for maintaining clinical response with tary patterns or lifestyle. Regular dietary follow-up of selected
FMT in Crohn disease patients was about 4 months.40 In an- donors may nearly be as important as screening for infections.
other study in patients with UC, all 9 patients who achieved re- Similarly, tracking the dietary habits and patterns of the re-
mission with FMT relapsed on follow-up.5 Maintenance therapy cipient are crucial. FMT attempts to restore the microbial
with FMT is, therefore, needed. A randomized pilot study from dysbiosis in UC. Once the dysbiotic microbiome is “corrected”
India, evaluated 8 weekly colonoscopic infusion of FMT for by FMT, it has to be sustained over time for a prolonged ben-
maintaining remission in UC. Patients who achieved clinical re- efit. The authors believe that, apart from maintenance FMTs,
mission with FMT were randomized to receive either FMT or a healthy diet that regulates gut homeostasis and maintains
placebo in addition to stable doses of 5-ASA plus azathioprine. a diversified microbiome, is vital for long-term response to
Among participants allocated to FMT plus pharmacotherapy FMT. Consumption of a “pro-inflammatory diet” (com-
27 of 31 (87.1%) were able to maintain steroid-free clinical re- prising of animal proteins, refined carbohydrates, n-6 polyun-
mission at week 48 vs 66.7% (20/30) patients assigned to the saturated fatty acids, food additives and emulsifiers, etc.) by a
pharmacotherapy alone (P = 0.111). Endoscopic [FMT: 18/31 FMT recipient is expected to increase the relative abundances
(58.1%) vs placebo: 8/30 (26.7%), P = 0.026] and histological of unfavorable microbes like Proteobacteria, Actinobacteria,
[FMT: 14/31 (45.2%) vs placebo: 5/30 (16.7%), P = 0.033] re- Bacillus species, Alistipes species, Bilophila species, Clostridium
missions were maintained in a significantly higher number of leptum, Escherichia coli, Mycobacterial species, Staphylococcus,
patients receiving FMT in addition to pharmacotherapy.41 Streptococcus, Klebsiella, Salmonella, and Pseudomonas species
The optimal interval between 2 sessions of FMT re- laying the foundation for persistence of an inflammatory mi-
mains to be determined. Microbial engraftment in patients lieu in the intestinal lumen, ultimately leading to therapeutic
with rCDI has been demonstrated to increase from days 2 to 6 inefficacy. The dietary patterns and practices of the donor and
after FMT and it plateaus by days 28 to 45. This engraftment is the recipient may thus influence the long-term effects of FMT.
typically sustained for months.42 However, in a persistent state Further studies addressing the optimal diets for recipients re-
of dysbiosis of UC, repeated FMT sessions are likely to be re- sponding to FMT are needed.
quired for sustained efficacy. Although there is no consensus,
intervals ranging from 1 to 12 weeks have been described.5–8,43 Assessing Response to FMT
In the Indian studies, a colonoscopic route for infusion of FMT Response to FMT depends on successful bacterial en-
was used and the sessions were scheduled at weeks 0, 2, 6, 10, graftment of the donor microbiota. However, many factors
14, 18, and 22 for induction of remission and subsequently like age, severity and behavior of underlying disease, genetic
every 8 weeks for maintenance of remission.9,41 The authors makeup of the patients, dietary patterns, indication for FMT,
acknowledge that multisession colonoscopic FMTs may not comorbidities, and concomitant medications can influence the
be an economically viable option in developed countries. But outcomes with FMT.
for developing countries where colonoscopies are not expen- Newer microbiota-targeted approaches including
sive (eg, US$50 per session in India) and use of biologics have bacterial genome reconstruction, studying functional ca-
constraints, FMT is an economically less demanding endeavor. pacity (including metabolomics, metaproteomics, and
The annual cost of FMT is comparable to the costs incurred on metatranscriptomics) and strain variation, and analyzing vir-
5-ASAs. However, it is an invasive and labor intensive proce- uses and eukaryotes (“kingdomagnostic” metagenomics) have
dure. This strategy of using frequent FMT sessions is not likely facilitated the assessment of the viability and engraftment of

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Crohn’s & Colitis 360 • Volume 2, Number 4, October 2020 Intestinal Microbiome Transfer in UC

transplanted gut microbiota.47 Successful engraftment is also same donor on different days. This poses a significant challenge
dependent on host immune responses and dietary patterns for the regulatory agencies since stool is unlike any other thera-
of both the donor and the recipient as they shape the mi- peutics approved for clinical use. Reports of transmission of
crostructure of gut microbiome.48 Li et al demonstrated that drug-resistant E. coli by FMT, though in immune-compromised
new microbial strains from the donor had a higher likelihood recipients, have further complicated the issue.55 As of now, there
of engrafting if the recipient already possessed that species.49 is no consensus on how FMT should be classified or regulated.
Further research focusing on these aspects will undoubtedly re- Currently FMT is regulated as a drug in Canada and in the
veal significant information and enrich the existent knowledge. United States and as a biologic in Australia; yet it remains un-
regulated in many countries. In North America, a treating phy-
sician can offer FMT to patients suffering from rCDI without
FMT in the COVID-19 Era the need to apply for an Investigational New Drug (USA) or
As the world reels under the coronavirus disease (COVID-
Clinical Trial Application (Canada), which are required for
19) pandemic, concerns regarding the screening of donors of
other indications. In the United Kingdom, a hospital can pre-
cellular or tissue-based products have been raised. The severe
pare FMT and treat its own patients under pharmacy exemp-
acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA
tion. If FMT is to be sent to another hospital, a special license
has been isolated from both intestinal tissue and fecal specimen.
would be required, and for use in a clinical trial, additional li-
Interestingly, the viral RNA is detected in fecal samples even after
cense (IMP license) is necessary. For many countries, an investi-
the respiratory samples test negative for COVID-19.50 The viral
gator simply needs to submit an application to the institutional
excretion in feces opens up the possibility for transmission of
ethics boards before conducting FMT trials. An entirely new
SARS-CoV-2 via feces, though the evidence is lacking at the mo-
framework is needed for the purpose of regulation. On the one
ment. Nevertheless, the international expert panel on FMT and
hand, we do need regulation of FMT for patient safety. At the
stool banking recognizes the risk and suggests screening of the
same time, we do not want to create barriers in the process to
donors for presence of typical COVID-19 symptoms (including
hinder patient access and scientific progress.
fever, fatigue, dry cough, myalgia, dyspnea, and headache) and
inquiring about history of travel/close contact with individuals
with proven or suspected infection, within the previous 30 days.51 NOMENCLATURE
The US Food and Drug Administration (FDA) recommends that The intestinal microbiome (comprising both structural
stool donated before December 1, 2019, can be used until proper and functional ecosystems of the microbial community) has an
testing and screening protocols are available.52 Development and important role in maintaining health and any imbalance in the
standardization of stool tests for SARS-CoV-2 have been a hurdle, composition and diversity can cause several diseases.56 The idea
though a protocol for stool SARS-CoV-2 viral quantification has that normalization of an altered microbiome and the restora-
been proposed.53 Since viral RNA can persist in stool even in the tion of balance alleviates disease is the backbone of the science
absence of respiratory symptoms, it may be prudent to test donors of transplantation (FMT). However, the term FMT seems to
at multiple timepoints. Appropriately equipped biosafety level 2 be a misnomer. The phrase fecal microbiota, in strict terms, re-
laboratories with trained staff and expertise in specimen handling fers only to luminal microbial community and does not repre-
would be required. sent the functional/metabolomic components. Substituting the
word “microbiota” with “microbiome” is likely to portray the
true picture.57 Secondly, the term transplantation denotes the
FMT Regulations process of taking an organ or living tissue and implanting it per-
FMT for patients with UC is still in an experimental stage
manently in another part of the body or in another body. FMT
and is currently not recommended as the standard of care. Its
is not precisely “transplantation” as the composition of trans-
use beyond clinical trials is therefore not recommended. Even
ferred microbiome is not constant and organism engraftment is
for rCDI the FDA exercises its discretion and places it under the
affected by various host and environmental factors. Therefore,
ambit of an investigational new drug. The experimental nature
replacing the word “transplantation” with “transfer” appears
of FMT, as well as its potential long-term consequences and the
scientifically logical. Although, the term FMT has been widely
likelihood of achieving therapeutic goals should be discussed
reported in the literature to date, and others have suggested an
with the patient in detail. FMT can be administered through
alternative,58 the authors believe that the term fecal microbiota
various routes, none of which is standardized at present. The re-
transplantation should be replaced by fecal microbiome transfer.
cipient should have sufficient opportunity to discuss and have all
of his/her questions answered to his/her satisfaction upon which
the informed decision about undergoing the procedure should THE WAY FORWARD
be made.54 FMT has caught the imagination of researchers around
Stool is a complex mixture. The exact composition of the globe. The future holds much promise for the potential ap-
FMT is not known, and will vary even if obtained from the plications of this approach in management of UC. Although our

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understanding of the microbiome and mucosal immune system 17. Chen HC, Chang CC, Mau WJ, et al. Evaluation of N-acetylchitooligosaccharides
as the main carbon sources for the growth of intestinal bacteria. FEMS Microbiol
is moving forward rapidly, the science of the gut microbiome is Lett. 2002;209:53–56.
still in its infancy and the clinical use beyond clinical trials is not 18. Ellermann M, Arthur JC. Siderophore-mediated iron acquisition and modulation
of host-bacterial interactions. Free Radic Biol Med. 2017;105:68–78.
recommended at the moment. Despite the encouraging results 19. Hooper LV, Macpherson AJ. Immune adaptations that maintain homeostasis
from clinical trials, many issues need to be settled. Selecting appro- with the intestinal microbiota. Nat Rev Immunol. 2010;10:159–169.
20. Rossi M, Bot A. The Th17 cell population and the immune homeostasis of the
priate patients and advancements in fecal slurry preparation and gastrointestinal tract. Int Rev Immunol. 2013;32:471–474.
mode of delivery are necessary. Many unanswered questions like 21. Francino MP. Early development of the gut microbiota and immune health.
Pathogens. 2014;3:769–790.
whether shifting to selective microbiota transplantation tailored 22. Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents
according to a particular disease can substitute the whole stool intestinal inflammatory disease. Nature. 2008;453:620–625.
23. Glover LE, Lee JS, Colgan SP. Oxygen metabolism and barrier regulation in the
with its biological and chemical ecosystems; or should the donors intestinal mucosa. J Clin Invest. 2016;126:3680–3688.
and recipients be matched for genotype, diet, or environment; and 24. Burrello C, Garavaglia F, Cribiù FM, et al. Therapeutic faecal microbiota trans-
plantation controls intestinal inflammation through IL10 secretion by immune
to what extent can diet modulate the intestinal microbiota to in- cells. Nat Commun. 2018;9:5184.
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DATA AVAILABILITY 27. Kelly CR, Kahn S, Kashyap P, et al. Update on fecal microbiota transplantation
Data sharing is not applicable to this article as no new 2015: indications, methodologies, mechanisms, and outlook. Gastroenterology.
2015;149:223–237.
datasets were generated or analyzed during the current report. 28. Woodworth MH, Neish EM, Miller NS, et al. Laboratory testing of donors
and stool samples for fecal microbiota transplantation for recurrent Clostridium
difficile infection. J Clin Microbiol. 2017;55:1002–1010.
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