JNM

J Neurogastroenterol Motil, Vol. 28 No. 1 January, 2022

pISSN: 2093-0879 eISSN: 2093-0887
https://doi.org/10.5056/jnm21221
Journal of Neurogastroenterology and Motility Review

Clinical Practice Guidelines for Fecal Microbiota

Transplantation in Korea

Tae-Geun Gweon,1 Yoo Jin Lee,2 Kyeong Ok Kim,3 Sung Kyun Yim,4 Jae Seung Soh,5 Seung Young Kim,6 Jae Jun Park,7
Seung Yong Shin,8 Tae Hee Lee,9 Chang Hwan Choi,8 Young-Seok Cho,1* Dongeun Yong,10 Jin-Won Chung,11 Kwang Jae Lee,12
Oh Young Lee,13 Myung-Gyu Choi,1 and Miyoung Choi14; Gut Microbiota and Therapy Research Group Under the Korean Society
of Neurogastroenterology and Motility
1
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea; 2Department of Internal Medicine,
Keimyung University School of Medicine, Daegu, Korea; 3Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Yeungnam University College of Medicine, Daegu, Korea; 4Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Jeonbuk National University Medical School and Hospital, Jeonju, Jeollabuk-do, Korea; 5Division of Gastroenterology and Hepatology,
Department of Internal Medicine, University of Hallym College of Medicine, Hallym University, Anyang, Gyeonggi-do, Korea; 6Division of
Gastroenterology and Hepatology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do, Korea;
7
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; 8Division
of Gastroenterology and Hepatology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea; 9Institute
for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea; 10Department of Laboratory
Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea; 11Division of Infectious Diseases,
Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea; 12Department of Internal Medicine, Ajou University
School of Medicine, Suwon, Gyeonggi-do, Korea; 13Department of Internal Medicine, Hanyang University School of Medicine, Seoul, Korea; and
14
Division of Healthcare Technology Assessment Research, National Evidence-Based Healthcare Collaboration Agency, Seoul, Korea

Fecal microbiota transplantation (FMT) is a highly efficacious and safe modality for the treatment of recurrent or refractory
Clostridioides difficile infection (CDI), with overall success rates of 90%. Thus, FMT has been widely used for 10 years. The incidence
and clinical characteristics of CDI, the main indication for FMT, differ between countries. To date, several guidelines have been
published. However, most of them were published in Western countries and therefore cannot represent the Korean national healthcare
systems. One of the barriers to performing FMT is a lack of national guidelines. Accordingly, multidisciplinary experts in this field have
developed practical guidelines for FMT. The purpose of these guidelines is to aid physicians performing FMT, which can be adapted to
treat CDI and other conditions.
(J Neurogastroenterol Motil 2022;28:28-42)

Key Words
Fecal microbiota transplantation; Guideline; Treatment

Received: November 16, 2021 Revised: None Accepted: December 8, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.
org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work
is properly cited.
*Correspondence: Young-Seok Cho, MD, PhD
Division of Gastroenterology, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary’s Hospital, 222
Banpo-daero, Seocho-gu, Seoul 06591, Korea
Tel: +82-2-2258-6021, Fax: +82-2-2258-2038, E-mail: yscho@catholic.ac.kr
Tae-Geun Gweon and Yoo Jin Lee equally contributed to this article.

ⓒ 2022 The Korean Society of Neurogastroenterology and Motility

28 J Neurogastroenterol Motil, Vol. 28 No. 1 January, 2022

www.jnmjournal.org
 Korean FMT Guidelines

gastroenterologists, 1 professor of infectious diseases, 1 professor of

laboratory medicine, and 1 methodologist invited from the National
Introduction Evidence-based Healthcare Collaborating Agency. Six workshops
Fecal microbiota transplantation (FMT) is a highly effica- were held for all working participants. The first meeting took place
cious and safe modality for the treatment of recurrent or refractory on July 31, 2019. After the outbreak of the novel coronavirus dis-
Clostridioides difficile infection (CDI), with overall success rates of ease 2019 (COVID-19), 4 of the 6 meetings were held online.
90%.1 With the great success of FMT for CDI and the develop-
ment of next-generation sequencing, FMT has been tested for a Development Process
range of other diseases including metabolic and gastrointestinal (GI) The working group decided to follow the adaptation method
diseases such as irritable bowel syndrome (IBS) and inflammatory for guidelines development. Seven guidelines were assessed for
bowel disease (IBD), and several guidelines have been published.2-6 suitability for adaptation using the Korean Appraisal of Guidelines
Although FMT has been tried for non-CDI diseases, the methods for Research and Evaluation II.7 After rigorous review, 5 guide-
and results are mixed. While previous guidelines focused on FMT lines were included for adaptation (Table 1).2-6 For recent articles,
for the treatment of CDI, both disease prevalence and healthcare MEDLINE, Embase, and Web of Science were searched for
systems are heterogenous across countries. Korean FMT guidelines literature that were published after the reference guidelines between
are needed because the lack of national guidelines is one of the ma- January 2017 and September 2020. Human clinical trials were
jor hurdles for FMT. In the guidelines developed here, we focus on mainly extracted. For quality assessment, the RoB 1.0 and Ro-
the practical aspects of FMT, rather than on indication and basis. BANS 2.0 tools were used for randomized controlled trials (RCTs)
and observational studies, respectively.8 Efficacy and safety should
be considered together for the practical aspects of FMT. Optimal
Methods FMT practice should be done to increase efficacy and minimize
adverse events (AEs). For CDI, the efficacy of the first FMT was
Direction reported to be about 80%. The overall efficacy of FMT can be in-
The process of FMT includes donor screening, production of creased by the performance of multiple FMTs.9,10 However, this is
stool material, and delivery. Therefore, multidisciplinary expertise accompanied by increased medical costs, inconvenience for the pa-
is involved in the development of these guidelines. Members of the tient, and the possibility of AEs. Therefore, physicians should try to
Gut Microbiota and Therapy Research Group of the Korean So- enhance the success rate of the first FMT. Since FMT has become
ciety of Neurogastroenterology and Motility (KSNM) are mainly widespread for various indications, several fatal AEs have been
involved in developing these guidelines. Multi-academic societies, reported to date regarding endoscopy-related complications and
including the Korean Society of Gastroenterology, the Korean So- infectious complications. We emphasize the safety issue of FMT in
ciety of Infectious Diseases, and the Korean Society for Laboratory these guidelines. Case reports or conference abstracts were included
Medicine, participated as well. The working group consisted of 11 regarding fatalities in cases of FMT.

Table 1. Selected Guidelines for Adaptation

Author Title Country Journal Year

Cammarota et al2 European consensus conference on fecal microbiota transplantation in clinical practice Europe Gut 2017
Mullish et al3 The use of fecal microbiota transplant as treatment for recurrent or refractory United Kingdom Gut 2018
Clostridium difficile infection and other potential indications: joint British Society of
Gastroenterology and Healthcare Infection Society guidelines
Cammarota et al4 International consensus conference on stool banking for fecal microbiota International Gut 2019
transplantation in clinical practice
Ng et al5 Scientific frontiers in fecal microbiota transplantation: joint document of Asia-Pacific Asia-Pacific Gut 2020
Association of Gastroenterology and Asia-Pacific Society for Digestive Endoscopy
Haifer et al6 Australian consensus statements for the regulation, production and use of fecal Australia Gut 2020
microbiota transplantation in clinical practice

Vol. 28, No. 1 January, 2022 (28-42) 29

Tae-Geun Gweon, et al

The guidelines and article assessments were performed by 2

independent members. In total, 103 articles were selected for the
resulting guideline. The working group formulated 18 statements
Inflammatory Bowel Disease
regarding methodology for FMT according to the quality of evi-
Statement 2: When fecal microbiota transplantation
dence and grade of recommendation (Table 2). Because there are
is performed in patients with inflammatory bowel
few experts in this topic, the Delphi method was not adopted. In-
disease, either for Clostridioides difficile infection or
stead, grade of recommendation was formulated through voting by
IBD treatment, a warning of inflammatory bowel dis-
members of the working group.
ease flare should be issued.
(Strong recommendation, high quality of evidence)
Fecal Microbiota Transplantation Indications IBD is a chronic and intractable intestinal disorder. Although
Statement 1: Fecal microbiota transplantation is rec- the causal relationship has yet to be determined, dysbiosis has been
ommended for patients with recurrent Clostridioides proved in patients with IBD. FMT has been tried in patients
difficile infection who have had at least 2 recurrences with IBD for the treatment of CDI or IBD itself.13-16 A recent
and can be considered in patients with refractory or population-based study reported that patients with underlying IBD
severe Clostridioides difficile infection. had a 4.8-fold higher risk of developing CDI than individuals with-
(Strong recommendation, high quality of evidence) out IBD. The risk of CDI in IBD patients is especially increased
among young patients and within the first year of diagnosis.17 A
Guidelines from the American College of Gastroenterology in systematic review reported that the mortality of CDI was higher in
2013 and Infectious Diseases Society of America and Society for IBD patients compared with non-IBD patients (odds ratio [OR],
Healthcare Epidemiology of America in 2018 recommend FMT 4.39; 95% confidence interval [CI], 3.56-5.42; I 2 = 93%).18 Stud-
for patients with second or subsequent recurrences of CDI who ies suggest that FMT is an effective option for the treatment of
have failed appropriate antibiotic therapy.11,12 In Europe and Austra- CDI in patients with underlying IBD. A recent systematic review
lia, guidelines or consensus statements strongly recommend FMT of 9 cohort studies reported that the initial cure rate was 81%, and
for the treatment of multiple recurrent CDI, and recommend that the overall cure rate after repeated FMT infusions was 89%,
FMT for refractory or severe CDI not responding to conventional suggesting that FMT is an effective treatment for recurrent CDI
antibiotic treatment.2-4,6 We recommend FMT for recurrent CDI in individuals with underlying IBD.19 A cohort study including 272
of at least 2 episodes. For refractory or severe CDI, FMT can be patients undergoing FMT for recurrent CDI showed that FMT is
considered at the physician’s discretion. To date, reports of efficacy less effective for treating recurrent CDI in IBD patients compared
of FMT for non-CDI diseases are mixed. When FMT is con- with those without IBD (74.4% vs 92.1%, P = 0.018).20
ducted for non-CDI diseases, it should be performed under regula- Some patients with IBD have been reported to have disease
tion or for the purposes of a clinical trial. flare after FMT. A large retrospective cohort study, including 67
patients, showed that a minority of patients (13%) had worsening

Table 2. Strength of Recommendation and Quality of Evidence

Strength of recommendation Position
Strong Most patients should receive the recommended course of action.
Conditional Different choices would be appropriate for different patients.
Quality of evidence Definition
High We are very confident that the true effect lies close to the estimate of the effect.
Moderate We are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of effect,
but there is a possibility that it is substantially different.
Low Our confidence in the estimate is limited. The true effect may be substantially different from the estimate of ef-
fect.
Very low We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the
estimate of effect.

30 Journal of Neurogastroenterology and Motility

 Korean FMT Guidelines

of disease.21 A systematic review, including 29 studies of 514 IBD to a specific region should be screened for region-specific endemic
patients, reported a pooled rate of IBD flare after FMT of 14.9%.22 diseases.
In subgroup analysis, the rate of FMT flare was 22.7% (95% CI, The first step toward donor screening is an interview for suit-
13-36%) in patients with CDI together with IBD, and 11.1% (95% ability for donation. Three key issues regarding the selection of
CI, 7-17%) in patients with IBD alone. The results of a prospective potential donors are as follows: (1) known history or risk factors for
study may be different from those of retrospective studies. A recent infectious diseases, (2) disorders potentially associated with pertur-
prospective multicenter study including 50 patients reported that bation of gut microbiota, and (3) drugs that can alter gut microbi-
disease activity in IBD after FMT was improved in 33 (67%), no ota. A questionnaire includes demographic characteristics, medical
change in 15 (31%), and de novo flare in 1 (2%), suggesting that condition, and recent travel history. The donor screening process,
IBD outcomes after FMT are better than reported in retrospective which was carried out in a single Korean center showed that 74% of
studies.23 Physicians should be aware of a possibility of IBD flare candidates were excluded based on this questionnaire,24 which was
after FMT, and patients should be informed of this risk. similar to data presented by other countries.25,26 The questionnaire
should be administered during screening and on the day of stool
donation.2,4 Even individuals who passed screening cannot donate
Donor Screening their stool if newly developed conditions are revealed by the ques-
tionnaire on the day of stool collection. The items for questionnaire
Statement 3: Stool donors should be assessed for gen-
and laboratory tests are summarized in Tables 3 and 4, respectively.
eral health status and gastrointestinal conditions by
Age is one of the most important risk factors for colorectal cancer.
clinical assessment, and serological and fecal tests.
Therefore, stool donation is recommended from young individu-
(Strong recommendation, low quality of evidence)
als aged < 45 years. For donors aged 45 years or above, absence
of colorectal cancer should be confirmed by colonoscopy within 3
Statement 4: Stool donors should repeatedly undergo
years of stool donation. Recently, young age onset colorectal cancer
the same clinical assessment, and serological and fecal
comprised up to 10% of total colorectal cancers in Korea. Colonos-
tests every 2-3 months.
copy might be done optionally for young donors aged < 45 years.
(Conditional recommendation, low quality of evidence)
Although colonoscopy can detect undetected colorectal diseases as
Donor screening is one of the most important steps for FMT. well as colorectal cancer, medical cost for donor screening should be
Stool can be obtained from a patient’s related donor or an unrelated considered. To date, transmission of colorectal cancer from donor to
donor (universal healthy donor). All donors should be approved for FMT recipient was not reported worldwide. Tests for transmissible
stool donation and this process should be done voluntarily. Donor infectious diseases should be included in stool and blood tests. In
candidates should be fully informed of the benefits and harms of stool tests, the United States (US) Food and Drug Administration
the donation and complete a written consent form. Donor’s infec- (FDA) recommends additional screening against multidrug-resis-
tious, metabolic, and other pathologic conditions can be transferred tant organisms (MDRO), because 2 previous case reports showed
to recipients. Therefore, a screening process including a clinical FMT-associated extended-spectrum beta-lactamases (ESBL)-
assessment, and serological and fecal tests should be carried out. producing Escherichia coli bacteremia.27 Therefore, screening for
Establishment of a non-profit stool bank has contributed to the MDRO was added to other viral, parasitic, and bacterial tests. In a
standardization of donor screening. In 2019, international guideline Korean study, only 19% of the initial donor candidate pool qualified
regarding donor screening was published.4 It is important to note as FMT donors after completion of overall screening.24 Although
that endemic diseases differ among countries. Tests for endemic the sample size of this report is much smaller than that of other
diseases that are specific to a region should be included along with countries,25,26 the results for suitability were acceptable. OpenBiome
common items for donor screening. High-risk countries include (Boston, MA, USA) reported that the pass rate of stool donation
regions at high risk of communicable disease/traveler’s diarrhea was only 3% among 15 317 eligible candidates.25 In consideration
(eg, South Asia, Africa, and the Middle East) and Creutzfeldt- of the extremely low rate of qualification for stool donation, interna-
Jakob disease (United Kingdom and Europe). In Korea, where the tional guidelines for stool banking have reported simplified general
prevalence of gastric cancer is high, donors should be screened for blood tests.4
Helicobacter pylori infection. Donors with a recent travel history

Vol. 28, No. 1 January, 2022 (28-42) 31

Tae-Geun Gweon, et al

CDI antibiotics (metronidazole or vancomycin) at least 24 hours

before administration of FMT. However, FMT is not a perfect
Preparation for Successful Fecal Microbiota treatment option for CDI.1,10 Considering FMT failure, it is chal-
Transplantation Delivery lenging for physicians to cease anti-CDI antibiotics, especially for
severe or fulminant CDI.34 Also, antimicrobial treatment can be
Antibiotic Discontinuation continued when primary infectious diseases were not resolved.

Statement 5: We suggest that fecal microbiota trans-

Bowel Lavage
plantation recipients with Clostridioides difficile in-
fection discontinue their antibiotics at least 24 hours Statement 6: We suggest bowel lavage before adminis-
before administration of fecal microbiota transplanta- tration of fecal microbiota transplantation. The ben-
tion. efits of bowel lavage should be balanced against the
(Conditional recommendation, low quality of evidence) problems faced by patients with swallowing difficulty
or at high risk of aspiration.
The ultimate goal of FMT is to restore the normal microbiome
(Conditional recommendation, low quality of evidence)
of the recipients’ intestine using healthy donors’ stools. Regardless
of the type of antibiotics, all antibiotics may adversely affect the When FMT is performed through colonoscopy, bowel lavage
FMT material. Therefore, most studies reported a washout period is essential. In addition to facilitating cecal intubation by removing
between completing antibiotics and administration of FMT. The solid material, pre-FMT bowel lavage may have several advantages
duration of the washout period varied from study to study. The such as eliminating residual antibiotics, C. difficile toxin, spores, and
shortest and longest durations were 4 hours28 and 3 days,29 respec- vegetative cells.35,36 Bowel lavage may facilitate both engraftment of
tively. The majority of studies advocated 24 hours.30-33 If possible, transplanted microorganisms and safe FMT procedures.3 In a me-
we recommend discontinuation of antibiotics for CDI and anti- ta-analysis, poor bowel preparation was an independent risk factor

Table 3. Clinical Assessment for Donor Candidates

General questions
- Date of birth
- Gender (pregnancy status if female)
- Height and weight
- Logistrics

Questions associated with infectious/transmissible diseases

- High-risk sexual behavior
- Recent travel history to high-risk countries
- Infectious disease risk (piercing, tattoos, and imprisonment)
- Any relationship with a person with a transmittable disease

GI-related questions
- Recent GI symptoms or disease
- Atopic syndrome, asthma, and allergies
- Autoimmune disease
- Chronic pain
- Mental health condition (depression, ADHD/ADD, anxiety)
- Neurologic disease (eg, Alzheimer’s and Parkinson’s)
- Medical history (surgery, malignancy, and other diagnoses)
- Restrictive diet or eating disorder
- Family history (GI disorder and colon cancer)
- Medication or supplement use within three months (eg, antibiotic, antifungal, antiviral, prescription medicine, and herbal medicine)
GI, gastrointestinal; ADHD, attention deficit and hyperactivity disorder; ADD, attention deficit disorder.

32 Journal of Neurogastroenterology and Motility

 Korean FMT Guidelines

Table 4. Serologic Screening and Stool Test for Donor Candidates

Serological screening
Viral tests
- Hepatitis A virus IgM
- Hepatitis B virus surface antigen
- Hepatitis C virus antibody
- HIV I and II
- Epstein-Barr virus (IgG and IgM)
- Cytomegalovirus (IgG and IgM)
Parasitic test: not applicable
Bacterial test
- Syphilis reagin test
Other blood tests
- Routine chemistrya
- Amylase/lipase
- C-reactive protein
- LDL/HDL cholesterol
- Triglyceride
- Antinuclear antibody test
- Erythrocyte sedimentation rate
- Insulin
- Complete blood count
- Platelet count
Stool tests
Viral tests
- Viruses associated with diarrhea (RT-PCR): Rotavirus, Norovirus, Adenovirus, Astrovirus
Parasitic tests
- Parasites and ova (multiplex PCR): Ascaris lumbricoides, Cryptosporidium parvum/hominis, Ancylostoma duodenale, Necator americanus,
Strongyloides stercoralis, Giardia lamblia, Entamoeba histolytica, Trichuris trichiura, Clonorchis sinensis, Diphyllobothrium latum,
Blastocystis hominis
Bacterial tests
- Helicobacter pylori (nested PCR)
- Bacteria associated with diarrhea (PCR): Salmonella spp., Shigella spp., Vibrio spp. Campylobacter spp. (C. jejuni, C. coli ),
Yersinia enterocolitica, and Aeromonas spp.
- Multidrug-resistant bacteria: MRSA (Cx), CRE (Cx + PCR), VRE (Cx + PCR), and ESBL-producing Enterobacteriaceae (Cx)
Additional fecal tests
- Fecal white blood cell
- Occult blood
Additional tests
Chest (posteroanterior) radiography
COVID-19 tests (only for pandemic period)
- Nasopharyngeal swab
- Serology for SARS-CoV-2
- Stool testing for SARS-CoV-2
a
Routine chemistry tests include tests for calcium, inorganic phosphate, glucose, blood urea nitrogen, creatinine, uric acid, total cholesterol, total protein, albumin,
alkaline phosphatase, aspartate transaminase, alanine aminotransferase, serum glutamate-pyruvate transaminase, and total bilirubin.
HIV, human immunodeficiency virus; LDL, low density lipoprotein; HDL, high density lipoprotein; RT-PCR, reverse transcription polymerase chain reaction;
PCR, polymerase chain reaction; MRSA, methicillin-resistant Staphylococcus aureus; Cx, culture; CRE, carbapenem-resistant Enterobacteriaceae; VRE, vancomy-
cin-resistant enterococci; ESBL, extended spectrum β-lactamase; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease
2019.

Vol. 28, No. 1 January, 2022 (28-42) 33

Tae-Geun Gweon, et al

for FMT failure.37 Therefore, bowel lavage was performed before suspension may be decreased while preserving the same quantity
FMT using the upper GI tract route, including oral capsules.30,38-40 of stool. The quantity of stool suspension differed among studies.
Bowel lavage carries a risk of vomiting and aspiration and may be In the first experience of frozen stool, the quantity of fecal suspen-
exempted for patients with high risk of aspiration.41 Adoption of sion presented was 220-240 mL, which contained 50 g of stool.46
bowel lavage should be conducted with caution for patients at high In a Korean stool bank (Microbiotics, Seoul, Korea), 125 mL of
risk of aspiration such as those with (1) swallowing difficulty, (2) fecal suspension contained 50 g of stool. In terms of efficacy, the
ileus, or (3) bedridden status. The benefits of bowel lavage should required quantity of stool for FMT should be at least 30-50 g. The
be weighed against the risks associated with high-risk groups. For stool quantity and method of FMT were heterogenous in studies
safety, polyethylene glycol is recommended for bowel lavage before on FMT for non-CDI. Therefore, it is challenging to define the
FMT. optimal quantity of stool for non-CDI FMT. The quantity of fecal
suspension should be restricted, especially for FMT via the upper
GI route. Infusion of a larger volume carries the risk of regurgita-
Factors Related to Fecal Microbiota Trans- tion or aspiration for upper GI tract infusions.47 The volume of
plantation Procedure fecal suspension should not exceed 250-300 mL for upper GI infu-
sions. For lower GI tract infusions, a larger-volume infusion may
Stool Amount not be related to AEs. Early evacuation of fecal suspension may
cause FMT failure or unintended spillage, which is an unpleasant
Statement 7: We recommend at least 30-50 g of stool
experience for recipients. Antiemetics for upper GI tract infusion
for fecal microbiota transplantation.
and loperamide for colonoscopic infusion may be helpful.
(Conditional recommendation, low quality of evidence)
There is limited information to determine the sufficient stool Stool Formulation
amount for FMT. In a recent systematic review including 168
Statement 8: If available, we recommend use of fro-
studies, the infused stool mass ranged from 25 g to 300 g.9 The
zen stool for fecal microbiota transplantation, which
optimal amount of stool differs among guidelines: 50 g for the Brit-
is manufactured from a stool bank or specialized insti-
ish guideline;3 30 g for the European guideline.2 The most recently
tute.
published guideline on stool banking recommends at least 25 g
(Strong recommendation, high quality of evidence)
based on the experience of OpenBiome.4
The British guideline recommends using > 50 g of stool in
Statement 9: Fresh stool, which was rigorously screened,
each FMT preparation based on the finding that the relapse rate
can be used for fecal microbiota transplantation.
after FMT was 4-fold higher when less than 50 g of stool was ad-
(Strong recommendation, high quality of evidence)
ministered (4% vs, 1% for ≥ 50 g).3,42 A recent meta-analysis also
confirmed that a fecal amount ≤ 50 g was associated with lower
Statement 10: A capsular product can be used for fecal
efficacy rates after a single infusion in recurrent CDI.43 Therefore,
microbiota transplantation for individuals without
it is important to provide a sufficient biomass to restore a healthy
swallowing difficulties.
microbiota, either by increasing the stool amount in each session,
(Strong recommendation, high quality of evidence)
or repeating infusion. In addition, there is wide variability in the
microbial content of stool samples between individuals and between In the developmental stage of FMT, fresh stool was used for
different donations, and the stool weight is an imperfect measure of FMT within 6-24 hours of evacuation. In 2012, Hamilton et al46
microbiota quantity.44 The development of a more objective mea- reported the process of manufacture and efficacy of frozen stool. In
sure of microbial richness and diversity could be more helpful than the US, frozen stool from a non-profit stool bank is the most com-
setting a specific amount. Regarding stool amount, only 1 study monly used formulation at the moment.48 Recently some novel stool
compared the efficacy of FMT between a higher amount and a formulations have been developed and investigated.49 However, the
lower amount of stool. For FMT in patients with IBS, 60 g of stool methods to manufacture these novel formulations are mixed and
showed better efficacy compared with 30 g.45 the efficacy of different formulations should be better investigated.
With advancement of stool processing, the quantity of fecal Therefore, we focused on comparing the efficacy between frozen

34 Journal of Neurogastroenterology and Motility

 Korean FMT Guidelines

Frozen Fresh Odds ratio Odds ratio Risk of bias

Study or subgroup Events Total Events Total Weight M-H, fixed, 95% CI M-H, fixed, 95% CI ABCDE F G
Jiang 2017 20 24 25 25 16.3% 0.09 [0.00,1.76]
Lee 2016 57 91 54 87 74.9% 1.02 [0.56, 1.88]
Mathew 2012 19 21 18 22 6.1% 2.11 [0.34, 12.97]
Satokari 2015 22 23 14 15 2.7% 1.57 [0.09, 27.21]

Total (95% CI) 159 149 100.0% 0.95 [0.56, 1.63]

Total events 118 111
2 2
Heterogeneity: Chi = 3.34, df = 3 (P = 0.34); I = 10% 0.01 0.1 1 10 100
Test for overall effect: Z = 0.18 (P = 0.86) Frozen Fresh
Risk of bias legend
(A) Random sequence generation (selection bias)
(B) Allocation concealment (selection bias)
(C) Blinding of participants and personnel (performance bias)
(D) Blinding of outcome assessment (detection bias)
(E) Incomplete outcome data (attrition bias)
(F) Selective reporting (reporting bias)
(G) Other bias

Figure. Forest plot of studies comparing frozen stool with fresh stool for fecal microbiota transplantation. M-H, Mantel-Haenszel.

stool and fresh stool for CDI. We included studies that compared aspiration, to date. We recommend FMT capsules for those with-
frozen and fresh stool. Single-arm studies were not included for out swallowing difficulty. More studies are needed to evaluate the
analysis. Two RCTs and 2 retrospective studies were included for efficacy of FMT treatment using capsule products.
meta-analysis.46,50-52 In total, 159 and 149 patients were included in
the frozen and fresh stool group, respectively. The success rate of Choice of Infusion Route
first FMT was 74.2% and 74.5% in the frozen and the fresh stool
Statement 11: When possible, colonoscopic infusion
group, respectively (OR, 0.95; 95% CI, 0.56-1.63; Figure).
of fecal suspension into the right colon (terminal il-
Considering the unsavory aspect of preparing fecal material,
eum or cecum) should be considered initially.
frozen stool provided by a certified stool bank is convenient for phy-
(Strong recommendation, high quality of evidence)
sicians because it makes the process of recruitment, screening of do-
nor stool, and preparation of a fecal suspension unnecessary. Fresh
Statement 12: Fecal microbiota transplantation en-
stool can also be used for FMT if the donor stool is rigorously
ema can be applied when fecal microbiota transplan-
screened, and stool processing is done in accordance with standard
tation via colonoscopy is not clinically appropriate.
processing.
(Conditional recommendation, high quality of evidence)
Capsule FMT is a promising formulation.40,53-55 Stool products
can be concentrated and prepared as capsules. Initially, capsules
Statement 13: Fecal microbiota transplantation via
contained concentrated liquid and were stored in a refrigerator.
upper gastrointestinal tract delivery can also be used
Subsequently, lyophilized capsules were developed. Lyophilized
where clinically appropriate. Upper gastrointestinal
capsules can be stored at room temperature, which is more ad-
tract should be avoided for patients with high risk of
vantageous compared with liquid capsules. The feces can be more
regurgitation or aspiration.
concentrated after lyophilization. One capsule of 0.65 mL contains
(Conditional recommendation, high quality of evidence)
1.6 g of stool.54,56 Currently, fresh, frozen, and capsular stool are
under investigation for CDI and non-CDI diseases. The resolution Fecal delivery can be performed via upper and lower GI tract.
of CDI with capsular FMT has been reported as 78-96%.40,51,56-58 Upper GI tract delivery is infusion of donor stools through a gas-
One RCT showed a comparable rate of CDI resolution after single troscope, nasogastric, nasojejunal, gastrostomy tube, or oral capsule.
FMT between capsule FMT and colonoscopic infusion (capsule, Lower GI tract delivery is used in the administration of donor
96% [51/53] vs colonoscopy, 96% [50/52]).40 FMT may be per- stools via colonoscopy, sigmoidoscopy, or retention enema. Choice
formed without the assistance of a physician using capsular stool. of infusion route is very important during the FMT procedure. Ef-
In terms of safety, no serious AEs has been reported, including ficacy and safety need to be considered together when adopting the

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Tae-Geun Gweon, et al

infusion route. In a nationwide registry of the US, 85% (221/249) scopic infusion is not indicated, the upper GI route infusion can be
of FMT was conducted using colonoscopy. Although the reason chosen. Patients should remain sitting for few hours after FMT.
for choosing the delivery method was not described in detail, the FMT using the upper GI route may be performed with or without
results of this study provide evidence that colonoscopic infusion is endoscopy (nasogastric tube and nasoduodenal tube). In a patient
the preferred method for FMT.48 survey, nasogastric infusion was the most unappealing infusion
We recommend colonoscopic FMT as the preferred infusion route for FMT.69 Endoscopic infusion may minimize patients’
route. Several systematic reviews and meta-analyses have revealed unpleasant sensations more so than methods other than endoscopy.
that the rate of successful FMT is significantly higher in patients Therefore, endoscopic infusion at duodenal second portion might
who received FMT via colonoscopy than other delivery meth- be recommended for FMT using upper GI route. Theoretically
ods.1,43,59,60 The most recently published meta-analysis reported that FMT using oral capsule can be regarded as upper GI tract FMT.
the overall cure rate of colonoscopic FMT was 94.8%. In a brief As discussed above, capsular FMT is favorable among upper GI
report from OpenBiome, FMT through colonoscopy showed bet- tract FMT, especially for patients without swallowing difficulty.
ter efficacy compared with the upper GI route.61 However, the stool However, capsular FMT has been regarded as different infusion
quantity of the 2 delivery routes differed. The provided stool quan- route, distinct from lower GI tract route or upper GI tract route.
tity was higher when FMT was performed using colonoscopy than The upper GI route is contraindicated for patients with frequent re-
that of the upper GI route. Researchers in the Netherlands pointed flux, vomiting, or ileus. When selecting a specific delivery route, an
out a limitation of the study and questioned the superiority of the individualized approach is needed that considers both the patient’s
lower GI tract route.62 Efficacy of FMT is affected by infusion clinical condition and local expertise.
route, bowel preparation, and quantity of stool. To date, there are
few studies comparing the efficacy of FMT according to infusion
route conducted under the same conditions.
Safety of Fecal Microbiota Transplantation
It is recommended that the infusion site of the lower GI access Statement 14: Patients should be informed of possible
using colonoscopy is the right colon.2,3 Guidelines suggest that the adverse events related to procedure and microbiota
preferred location for delivery of FMT is the cecum or terminal il- transfer before fecal microbiota transplantation.
eum, as this procedure may give the highest efficacy. Moreover, the (Strong recommendation, low quality of evidence)
ideal posture of a patient during FMT using colonoscopy has yet to
be elucidated. From an anatomical point of view, in order to increase Statement 15: The overall risk of adverse events of
the retention time of fecal suspension in the intestine, it is estimated fecal microbiota transplantation via lower gastrointes-
that the right lateral decubitus posture is more advantageous than tinal tract seems to be lower than that of upper gas-
the left decubitus posture during and after fecal infusion. For a se- trointestinal tract.
verely inflamed colon, colonoscopic infusion should be avoided. In (Conditional recommendation, moderate quality of evidence)
such cases, upper GI tract (upper endoscopy or capsule) or, alterna-
tively, the lower GI route (enema or sigmoidoscopic infusion) may FMT has been reported to be safe for the treatment of recur-
be chosen. rent CDI even in immunocompromised or organ transplantation
Although there is some evidence that FMT enema is less effec- individuals.39,70,71 Serious AEs (SAEs) were observed in 3.2% of
tive than FMT via colonoscopy,10,60 FMT enema has the practical cases, and there was no FMT-related bacteremia after solid organ
benefits of making FMT easily applicable, being less invasive than transplantation.71 In a cohort study including 7 CDI patients un-
colonoscopy, and allowing repeated FMT.50,63 Where fecal infusion dergoing hematopoietic stem cell transplantation, FMT was effec-
is performed using an enema, it is advised that the patient retains the tive (86% of cure rates) and safe.72 A systematic review including
stool for at least 30 minutes after the fecal suspension infusion and 303 immunocompromised patients with CDI showed that 87%
maintains a supine position to minimize bowel movement.2,50 A recent had resolution after the first FMT, with 93% treatment success
meta-analysis reported that multiple infusion FMT showed a high after multiple FMTs. Reported AEs included 2 FMT-non related
success rate,43 and thus repeated FMT enema can be considered. deaths, 2 colectomies, 5 bacteremias or infections, and 10 subse-
Alternative delivery routes include nasoduodenal tube,64,65 quent hospitalizations.73 In patients with liver cirrhosis undergoing
upper GI endoscopy,30,41,45,66-68 and enteroscopy.47 When colono- FMT, the cure rate of CDI was 86% (54/63 patients), and only 5

36 Journal of Neurogastroenterology and Motility

 Korean FMT Guidelines

possibly related SAEs occurred.74 A retrospective study from Israel mize the possibility of transfer of donor’s enteric pathogens. Even
including 34 patients aged 60 years or older with at least 1 signifi- so, all pathogens cannot be perfectly screened. Therefore, some
cant comorbidity showed a 90% clinical improvement with a few studies have investigated the efficacy of mixtures of purified bacte-
SAEs including suspected aspirations, suggesting that FMT is ef- rial strains, bacterial debris, or novel formulations.82,83
ficacious and safe for elderly patients with underlying illness.75 In terms of infusion route, nasal stuffiness, sore throat, rhinor-
Recently, some fatal AEs were reported and the safety of FMT rhea, and upper GI hemorrhage, were considered as definitely as-
was questioned.76-78 Before FMT, physicians should discuss with sociated with upper GI routes of administration.76,84,85 In addition,
their patients or clinical trial participants the risks associated with some of the common AEs after upper GI administration of FMT
the procedure. The choice of delivery route needs to be based on the are nausea and reflux.65,66 When performing FMT via the upper
specific clinical situation. AEs of FMT include procedure-related GI tract, one of the main concerns is regurgitation of fecal suspen-
complications and factors related to microbiota transfer. sion, which can lead to aspiration pneumonia, which in some cases
AEs can be classified as short- or long-term according to the can be fatal.47,65,76,86 Abdominal discomfort, one of the most frequent
interval between FMT and the occurrence of the AE. Short-term AEs associated with FMT, was reported in 29.9% (61/204) of
AEs include abdominal pain, diarrhea, flatulence, transient fever, patients after FMT by the upper GI route. For the lower GI route,
and procedure-related AEs.78 A systematic review including 129 13.0% (56/430) of patients developed abdominal discomfort after
studies (4241 patients) from years 2000 to 2020 documented the FMT. The upper GI route was more likely to develop abdominal
incidence of FMT-related AEs. The results showed that FMT- discomfort compared with the lower GI route.87 The exact mecha-
related AEs were identified in 19% of FMT procedures. Com- nism of higher incidence of abdominal discomfort for upper GI
monly reported immediate AEs after FMT were GI complications, infusion was not described. The small bowel is the longest part of
including diarrhea (10%), abdominal discomfort/pain/cramping GI tract. Despite limited information of the ecosystem of the small
(7%), nausea/vomiting (3%), and flatulence (3%). Most of these bowel, the diversity and density of microbiota in the small bowel
symptoms were self-limiting and disappeared within a few days. are lower than those of the colon.88 Large quantities of transferred
FMT-related SAEs, such as infections and deaths, were reported in donor’s microbiota may cause small intestinal bacterial overgrowth
59 patients (1.4%). Of 5 deaths, 4 were definitely FMT-procedure (SIBO) or adverse interactions between host and donor microbiota.
related, including 1 case of aspiration during sedation and 3 cases of Some cases of SIBO were reported after FMT to date.89 SAEs also
aspiration of the fecal suspension. One was probably FMT-related.79 have been reported regarding colonoscopic infusion. Bowel perfora-
The human gut microenvironment is regarded as an ecosys- tion was reported after colonoscopic delivery.90 Deaths related to
tem. Therefore, transfer of donor microbiota may cause donor– aspiration was also reported after FMT using colonoscopy.70 For
host reaction. Long-term safety or immunologic effects of FMT patients with high risk of aspiration, the decision to perform FMT
are relatively uncertain, including the occurrence of latent infections should be taken with caution.
and diseases or conditions related to changes in gut microbiota. One Few studies have reported that both upper GI route and lower GI
study reported the occurrence of peripheral neuropathy, Sjogren’s route were safe, with low incidence of AEs.66,91 However, in a system-
disease, idiopathic thrombocytopenic purpura, and rheumatoid atic review the rate of AEs was higher in the upper GI route than in
arthritis.29 However, the relationship between FMT and these con- the lower GI tract infusion.79 Death related to FMT was reported in 5
ditions is not clear. One study found that IBS developed in 4% of cases. Of these, there was 1 case of mortality after colonoscopic infusion.
patients after FMT.80 Observational studies have demonstrated that
FMT is relatively safe during long-term follow up.48,80
Transfer of pathogens is one of the serious concerns of FMT.
Follow-up After Fecal Microbiota Transplan-
The FDA has reported 6 cases of transfer of E. coli from the donor.
tation
Of these, 2 patients expired after FMT because of Shigatoxin-pro-
ducing E. coli .27 The donor’s stool was not tested for these bacteria Statement 16: All fecal microbiota transplantation
at that time. The FDA has requested that testing for MDRO such recipients are required to undergo follow-up in order
as carbapenem-resistant Enterobacteriaceae, vancomycin-resistant to assess treatment efficacy, disease recurrence, and
enterococci, and ESBL producing Enterobacteriaceae should be possible adverse events.
included in donor screening.81 Vigorous donor screening can mini- (Strong recommendation, high quality of evidence)

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Tae-Geun Gweon, et al

Statement 17: The first week after fecal microbiota

transplantation is important to identify symptom reso- Fecal Microbiota Transplantation During
lution and short-term adverse events, especially in COVID-19 Pandemic
patients with Clostridioides difficile infection.
(Strong recommendation, moderate quality of evidence) COVID-19 arising from the emergence and spread of severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rap-
Statement 18: The evaluation of primary outcome idly progressed into a global pandemic. Emerging evidence shows
should be performed at least 8 weeks after fecal mi- that SARS-CoV-2 RNA and/or SARS-CoV-2 virus may be found
crobiota transplantation. in stools of infected individuals and viral RNA may remain positive
(Strong recommendation, moderate quality of evidence) in stools even when viral RNA in the respiratory tract is no longer
detectable. These results suggest the possibility of transmission of
Post-FMT follow-up is required to evaluate efficacy and AEs. SARS-CoV-2 via a fecal-oral route.103,104 International expert panels
However, the follow-up duration and modality vary consider- recommend that at least a nasopharyngeal swab and serology should
ably between studies. The definition of cure in studies targeting be considered in potential FMT donors.105 Another expert opinion
recurrent and/or refractory CDI is mostly resolution of symptoms recommends that FMT should be delayed until COVID-19 is
including reduction of stool frequency and improvement of stool better controlled and may be performed only in cases of fulminant
consistency, generally over a period of several days. However, out- CDI without response to maximal combination therapy.106 Ng et
come parameters including symptom-free days, recurrence of CDI, al107 reported that a single negative study for stool does not guar-
and AEs have been assessed for more than 8 weeks. The first week antee the absence of SARS-CoV-2, and that testing donors at dif-
after FMT is important to identify short-term AEs and resolution ferent time points during the donation period is required. Further
of CDI. In studies selected by our committee, 2 studies, including research to develop a simple and effective method to find SARS-
an RCT, defined primary outcome as a progressive reduction in CoV-2 in stool samples is necessary until herd immunity is reached
diarrhea and clinical improvement within 1 week after FMT in by COVID-19 vaccination. Screening for SARS-CoV-2 should be
patients with CDI.92,93 In other studies, the short-term duration of considered in all donors and recipients if the pandemic persists.
follow-up ranged between 2 weeks and 1 month.71,91,94 When FMT In South Korea, there was an outbreak of Middle East Respi-
is conducted for CDI, symptom resolution was achieved within 1 ratory Syndrome in 2015. Widespread overseas travel can spread
week of FMT.30,95,96 In cases of primary non-response to FMT, any types of infectious diseases that are rare in Korea across the
repeated FMT may increase the overall cure rate.10 Therefore, re- country. During outbreaks of fatal infectious diseases, stool screen-
peated FMT or rescue therapy, such as oral vancomycin, should be ing should be performed in a strict manner and FMT may be bet-
considered at 1 week after FMT for non-response to FMT. When ter performed on a limited basis.
FMT is performed other than for CDI, the primary endpoint may
differ among studies. Short-term AEs should be followed at 1 week
after FMT.
Conclusion
Symptoms and recurrence of CDI, and AEs after FMT In this guideline, established by multidisciplinary academic
should be monitored over 2 months. The most common follow- societies, we provide the best practice for FMT in terms of efficacy
up period of primary outcome in CDI studies was about 2 and safety.
months.51,64,97,98 The studies defined the primary endpoint as clinical
resolution and/or absence of CDI recurrence. Early relapse after Financial support: This research was supported by a grant of
the Korea Health Technology R&D Project through the Korea
resolution of CDI is related to residual toxin from C. difficile . Some
Health Industry Development Institute (KHIDI), funded by the
studies followed the patients up to 3 months.38,40,50,99 Other studies
Ministry of Health & Welfare, Republic of Korea (Grant No.
used 13 weeks,50 120 days,100 and 6 months.101,102 The British guide-
HI19C0481, HC20C0099).
line recommends that all FMT recipients should be monitored
for at least 8 weeks in total to fully establish efficacy and AEs.3 For Conflicts of interest: None.
FMT other than for CDI, the primary outcome will be followed
until a predefined period. Author contributions: Tae-Geun Gweon have contributed in

38 Journal of Neurogastroenterology and Motility

 Korean FMT Guidelines

writing and editing the paper as the first authors; Miyoung Choi 2019;49:354-363.
helped in formulating clinical key questions, conducting relevant 10. Tariq R, Pardi DS, Bartlett MG, Khanna S. Low cure rates in con-
trolled trials of fecal microbiota transplantation for recurrent Clostridium
literatures search, and mentoring for extensive meta-analyses; Yoo
difficile infection: a systematic review and meta-analysis. Clin Infect Dis
Jin Lee, Kyeong Ok Kim, Sung Kyun Yim, Jae Seung Soh, Seung 2019;68:1351-1358.
Young Kim, Jae Jun Park, Seung Yong Shin, Tae Hee Lee, Chang 11. Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis,
Hwan Choi, Young-Seok Cho, Dongeun Yong, and Jin-Won treatment, and prevention of Clostridium difficile infections. Am J Gas-
Chung have contributed in the systematic review, the extraction troenterol 2013;108:478-498.
of recommendations, and writing the paper; Kwang Jae Lee, Oh 12. McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guide-
lines for Clostridium difficile infection in adults and children: 2017
Young Lee, and Myung-Gyu Choi have contributed as expert pan-
update by the infectious diseases society of America (IDSA) and society
el; and Young-Seok Cho has designed the guideline development as for healthcare epidemiology of America (SHEA). Clin Infect Dis
chairman of the Gut Microbiota and Therapy Research Group of 2018;66:e1-e48.
KSNM and have revised the manuscript critically. 13. Paramsothy S, Kamm MA, Kaakoush NO, et al. Multidonor intensive
faecal microbiota transplantation for active ulcerative colitis: a ran-
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