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Journal of the Formosan Medical Association (2018) xx, 1e9

Available online at www.sciencedirect.com

ScienceDirect

journal homepage: www.jfma-online.com

Review Article

Fecal microbiota transplantation: Review

and update
Jiunn-Wei Wang a,b, Chao-Hung Kuo a,c,d, Fu-Chen Kuo e,
Yao-Kuang Wang d, Wen-Hung Hsu a,c, Fang-Jung Yu a,c,
Huang-Ming Hu b,c, Ping-I. Hsu f, Jaw-Yuan Wang g,
Deng-Chyang Wu a,c,*

a
Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University
Hospital, Kaohsiung, Taiwan
b
Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
c
Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
d
Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
e
School of Medicine, College of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
f
Division of Gastroenterology, Kaohsiung Veterans General Hospital, National Yang-Ming University,
Kaohsiung, Taiwan
g
Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University, Hospital,
Kaohsiung, Taiwan

Received 8 August 2018; accepted 9 August 2018

KEYWORDS Fecal microbiota transplantation (FMT) is a method to directly change the recipient’s gut mi-
Fecal microbiota crobiota to normalize the composition and gain a therapeutic benefit. The history of FMT has
transplantation; been traced back to the 4th century and has been highly regarded since 2013, when the United
Intestinal microbiota States Food and Drug Administration approved FMT for treating recurrent and refractory Clos-
tridium difficile infection. Since then, the range of FMT applications extended rapidly and
broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor
selection with questionnaire, interview, blood tests, and stool examinations should be strictly
performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step
cautious fecal and recipient preparation along with adequately choosing delivery methods
based on individual clinical situations are key points of the FMT process. Although current ev-
idence deems FMT as a generally safe therapeutic method with few adverse effects, the long-
term outcomes of FMT have not been completely elucidated. Therefore, establishing period-
icity and length of regular follow-up after FMT to monitor the clinical efficacy and long-
term adverse events are other essential issues. In the future, we will look forward to person-
alized FMT for different patients and conditions according to varied hosts and diseases.

* Corresponding author. Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
Medical University, 100 Tz-You 1st Road, Kaohsiung 807, Taiwan. Fax: þ886 7 3135612.
E-mail address: dechwu@yahoo.com (D.-C. Wu).

https://doi.org/10.1016/j.jfma.2018.08.011
0929-6646/Copyright ª 2018, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Wang J-W, et al., Fecal microbiota transplantation: Review and update, Journal of the Formosan
Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.011
 + MODEL
2 J.-W. Wang et al.
Copyright ª 2018, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
Introduction
The human gastrointestinal (GI) tract is colonized by numerous
bacterial species, which have the function of aiding digestion,
assisting in nutritional provision, facilitating maturation of the
colonic epithelium, and protection from pathogens.1e3
Human gut microbiome differs by individual and is relatively
stable and resilient over time; however, environmental fac-
tors, including diet, probiotics, prebiotics, viruses, and drugs,
particularly antibiotics, can alter the composition.4e7 Many
different groups of diseases are connected to the gut micro-
biota, including infectious conditions (infectious gastroen-
teritis, Clostridium difficile infection (CDI)), autoimmune
diseases (allergic disease, diabetes, inflammatory bowel dis-
ease (IBD)), some general conditions (overweight, functional
GI disorders), and behavioral diseases.8 Currently, a wide va-
riety of medical therapeutic strategies are used to correct gut
dysbiosis, but a great majority of them do not present satis-
factory clinical effects, except for fecal microbiota trans-
plantation (FMT). FMT, namely stool transplantation, is a
method that places stool from a healthy donor into another
patient’s GI tract to directly change the recipient’s gut
microbiota to normalize the composition, gaining therapeutic
benefit.9,10 Currently, multiple studies have proven FMT as a
successful therapy for recurrent and refractory CDI, even in
patients who have comorbid conditions or are
immunosuppressed.11e13 Beyond the application in CDI, more
extensive use of FMT has been seen in recent years.14
History of fecal microbiota transplantation
The first records of FMT has been traced back to the fourth
century China, where human fecal material was called yellow
soup and was used in patients of severe diarrhea.15 Until China
Ming Dynasty in the sixteenth century, there were descriptions
of fresh or fermented fecal suspensions applied in patients
with GI conditions, including diarrhea, constipation, and
abdominal pain.15 Eiseman and his colleagues successfully
treated patients with FMT for pseudomembranous colitis in
1958, the first report in the medical literature.16 Italian sur-
geon Acquapendente created the term “transfaunation,”
which means transference of gastrointestinal content from a
healthy to a sick animal, and was applied extensively in the
field of veterinary medicine.17,18 Els et al. carried out the first
randomized controlled trial in 2013. The study showed that
duodenal infusion of donor feces in patients with recurrent CDI
had more significant efficacy in resolving symptoms than an-
tibiotics use alone.19 Since that time, increasing subsequent
case studies have proven high cure rates of recurrent and re-
fractory CDI with FMT. Additionally, the earliest record of FMT
applied in a non-infectious disease was published in 1989.
Borody et al. performed “an exchange of bowel flora” on a 45-
year old male with refractory ulcerative colitis (UC), showing
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Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.011
full and lasting clinical recovery after treatment.20 After the
clinical use of FMT shifted from infectious to non-
communicable disorders, the range of FMT applications
extended rapidly. Moreover, new insights connecting gut
microbiota to the extraintestinal diseases would further
broaden the clinical practice of FMT.
Indications and contraindications
Most current clinical experience with FMT has originated
from treatment of recurrent or refractory CDI.21 Multiple
studies have demonstrated remarkable effectiveness of
FMT in cases of recurrent and refractory CDI, which may
be attributed to sustained restoration of the normal
microbiota after FMT.22,23 The cure rate is surprisingly up
to approximately 90% in recurrent or refractory CDI, which
is much superior to prolonged anti-microbial therapy with
20e30% success rates.19,24,25 As a result, it is now already
listed in several expert guidelines of standard practice for
treating recurrent and refractory CDI,10 and it is the only
indication approved by the United States (US) Food and
Drug Administration (FDA) since 2013.26 Apart from CDI,
there is a high level of interest in FMT use as a potential
therapy targeting IBD. Promising case reports and
increasing clinical trials demonstrated that FMT may play
a useful primary therapeutic role.27e30 However, response
rates have not been as impressive as FMT for the indica-
tion of CDI. Therefore, modified strategies of FMT use,
step-up or intensive-dosing multidonor FMT, were per-
formed in IBD patients and indicated beneficial treatment
responses.30,31 Furthermore, current studies demon-
strated FMT can be a cost-saving intervention in managing
recurrent and refractory compared to antibiotics use and
in moderate-to-severe IBD treatment.32,33 In addition,
some clinical trials have applied FMT in functional bowel
disorders. Several meta-analysis and cohort studies have
shown improved bowel movement in irritable bowel syn-
drome patients after FMT.18,34e36 Beyond the gastroin-
testinal disorders, the applications of FMT rapidly
expanded to multiple fields of extra-gastrointestinal dis-
eases in recent years. Several studies have evaluated the
prospect of altering the gut microbiome as a potential
therapy for obesity and the metabolic syndrome.37e39
Vrieze and colleagues administered FMT in patients with
metabolic syndrome, and a significant increase in insulin
sensitivity in these subjects was proven after treatment.40
Several case reports and animal models have also revealed
the probable therapeutic effects of FMT in patients with
severe multiple sclerosis,41 autism,42 multidrug-resistant
organisms (MDRO) infections,43 and multiple organ
dysfunction in critical patients.44 Furthermore, recent
studies also demonstrated the positive effects of immu-
notherapy on melanoma with FMT in an animal model and
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Fecal microbiota transplantation 3

clinical trial.45,46 The summary of current and potential
indications is shown in Table 1.41e44,47,48 In contrast, there
is no known absolute contraindication for FMT based on
the current clinical evidence.11
Donor selection
To reduce and prevent the occurrence of adverse events,
strict donor screening tests of FMT are recommended.47,49
The guidelines in the United States and European consensus
conference both suggest to use a donor questionnaire to
meet the exclusion and inclusion criteria (Table 2).21,49e52 To
evaluate any recent potentially harmful behaviors, screened
donors should undergo an additional interview on the same
day of the donation.49 Furthermore, standard donor
screening protocols should be set up to lower the risks of
infection transmission from the donor to recipient, and a
suitable donor ought to receive both blood and stool exami-
nations within 4 weeks before donation (Table 3).49,51,52 A
spouse or close relative was historically considered as an
ideal FMT donor. Fecal material from the spouse might
minimize the risk of infection transmission because shared
environmental risk factors. The similarity of microbial spe-
cies is expected between the recipient and his/her close
relative; therefore, adaptive immunity in the mucosal im-
mune system might present more tolerance towards the
microbiota from the donor.50 Nevertheless, additional clin-
ical evidence has proven no association between donor and
FMT outcomes.53,54 Unrelated FMT volunteer donors may be
more beneficial in cases where genetics play a contributing
factor in the disease, like IBD.55 Certainly, the time between
screening and donation is another important issue. The FMT
French group recommend that the period must be as short as
possible without exceeding 21 days in order to reduce the risk
of contamination.56 In sum, selection of an adequate donor is
a key point in FMT.
Fecal preparation
The optimal preparation of fecal material to manage re-
mains to be determined. It had been debated whether fresh
or frozen fecal material was the better choice for FMT at
the beginning of the FMT practice. Currently, several ran-
domized clinical trials and meta-analysis demonstrated
that frozen FMT has the same efficacy as fresh FMT in
clinical improvement of recurrent or refractory CDI.57e59
Fresh fecal material should be processed within 6 h of
donor production, and it can be stored at room tempera-
ture until further processing. Approximately 50 g (minimum
amount of 30 g) of fecal material is mixed with approxi-
mately 150 mL of sterile normal sodium chloride by
blender. The mixture is filtered with a filter or gauze to
clear away large particulate matter, which may obstruct
the endoscope channel. Finally, the filtrate is infused into
60-mL syringes (generally 4e5 tubes) and infused to the
recipient’s GI tract.49,52,56 In recent years, several stool
banks have been established worldwide in succession.
Collecting stool from a set of prescreened donors, prepar-
ing and dividing the donated fecal material, and freezing
aliquots of screened fecal material are processed in a stool
bank. Additionally, the final fecal material must be strictly
managed by clearly labeling, tracking, and storing at
80  C. On the day of FMT, the fecal suspension is thawed
in a warm (37  C) water bath, and the normal saline solu-
tion is mixed to obtain an expected suspension volume. It is
worth noting that repetitive thawing and freezing ought to
be avoided, and infusion should be performed within 6 h of
thawing.49,52 Nevertheless, the appropriate volume of fecal
infusion is difficult to define. Larger volumes of fecal ma-
terial have shown better FMT outcomes in CDI patients, as
demonstrated by a systemic review article, and up to a
four-fold higher risk for failure was noted for infusion vol-
umes less than 50 g compared to the larger volume.24
Recipient preparation
Regardless of the source of fecal material or chosen route
of administration, patients undergoing FMT need support
and education prior to treatment.60 Recipient should not be
administered with any form of antibiotics 12e48 h before
fecal infusion.49 Practical preparation for the FMT proced-
ure is similar to that of any other endoscopic procedure,
including a standard bowel preparation. The bowel should

Table 1 Current and potential indications of fecal microbiota transplantation.

Current indication
Recurrent and refractory Clostridium difficile infection
Indications in investigation and potential indications
Gastrointestinal diseases
- Inflammatory bowel disease (Ulcerative colitis, Crohn’s disease)
- Functional bowel disorders (Irritable bowel syndrome, Constipation)
Extra-gastrointestinal diseases
- Metabolic syndrome (Type 2 diabetes, Nonalcoholic steatohepatitis)
- Obesity
- Autoimmune disorders
- Parkinson’s disease
- Autism
- Multiple sclerosis
- Idiopathic thrombocytopenic purpura
- Multidrug-resistant organisms infections
- Multiple organ dysfunction in critical patients

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 + MODEL
4 J.-W. Wang et al.

Table 2 Donor inclusion and exclusion criteria.

Inclusion criteria
Aged 18e65 year
No history or current symptoms of gastrointestinal disease
No other major active medical comorbidities
Minimal regular medications with no medications that may interfere with stool viability, including no antimicrobials
(antibiotics, antifungals, antivirals)/probiotics in the preceding 3 months
Exclusion criteria
Risk of infectious agent
 Known HIV, hepatitis B, or hepatitis C infection
 Known exposure to HIV or viral hepatitis within the previous 12 months
 High risk sexual behavior (e.g., sexual contact with anyone with HIV/AIDS or viral hepatitis, men who have sex with men,
sex for drugs or money)
 Use of illicit drugs
 Tattoo or body piercing within the preceding 6 months
 Known current communicable disease (e.g., upper respiratory tract infection)
 Risk factors for variant CreutzfeldteJakob disease
 Travel within last 6 months to areas of the world where diarrheal illnesses are endemic or risk of travelers’ diarrhea is high
Gastrointestinal comorbidities
 History of or current IBD
 History of or current irritable bowel syndrome, chronic constipation, chronic diarrhea, or other intrinsic gastrointestinal
illness/condition
 History of or current gastrointestinal malignancy or known polyposis or strong family history of colorectal cancer
 History of major gastrointestinal surgery (e.g., gastric bypass, partial colectomy)
Factors that can affect the composition of the intestinal microbiota
 Antimicrobials (antibiotics, antifungals, antivirals) or probiotics within the preceding 3 months
 Major immunosuppressive medications (e.g., calcineurin inhibitors, biological agents, exogenous glucocorticoids)
 Systemic antineoplastic agents
 Household members with active gastrointestinal infection
Other conditions
 Systemic autoimmunity (e.g., multiple sclerosis, connective tissue disease)
 Atopic disease (e.g., moderateesevere asthma, eczema, eosinophilic disorders of the gastrointestinal tract)
 Metabolic syndrome, obesity (BMI > 30), or moderate-to-severe undernutrition/malnutrition
 Chronic pain syndromes (e.g., chronic fatigue syndrome, fibromyalgia) or neurologic/neurodevelopmental disorders
 History of malignant illness or ongoing oncologic therapy
 Incarceration or long-term care facility residence
 Body piercing or tattoo in prior 6 months
Abbreviation: HIV: human immunodeficiency virus, AIDS: Acquired immune deficiency syndrome, IBD: Inflammatory bowel disease, BMI:
Body mass index.

be virtually free of contaminated fecal material prior to the
donor feces infusion to ensure a healthy graft.60 Some
studies suggested loperamide use one hour before FMT in
order to ensure that the transplanted feces stay at least 4 h
long in the intestines.61e63
Delivery methods
The current administration of fecal material by means
include upper GI route (via esophagogastroduodenoscopy
(EGD), nasogastric, nasojejunal, or nasoduodenal tube),
lower GI route (via colonoscopy or retention enema), and
oral capsule. In general, FMT via the upper GI route can be
administered in patients with an inflamed colon; however,
the discomfort sensation during tube placement, risks of
aspiration, and inability to evaluate the colon mucosa or to
collect mucosa tissue samples are weak points. FMT via
colonoscopy has superiority in recolonizing the entire colon
with favorable bacteria, and bowel cleaning can probably
reduce the number of residual organisms and spores to
visualize the entire colon, but it is a relatively risky,
expensive, and invasive procedure. FMT via retention
enema is more affordable and less invasive than colonos-
copy, but the donor fecal material cannot be delivered to
the entire colon and is limited to the distal colon. Although
the efficacy of retention enema had been once doubted,
Orenstein and Dubberke et al. have proven it more efficient
and safe than placebo in phase I and phase II recurrent CDI
clinical trials.64,65 Oral capsule for FMT administration has
the advantages of less invasion and high patient accept-
ability, but the expense and large capsule burden are its
disadvantages.52,66 There have been a number of studies to
evaluate the various methods of FMT administration.
Youngster et al. conducted a randomized pilot study
comparing upper and lower GI routes of FMT, and the report
found a non-significant difference in cure rate between the
two different administration methods.67 However, another

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Fecal microbiota transplantation 5

Table 3 Donor screening investigations.

Blood testing
Cytomegalovirus
EpsteineBarr virus
Hepatitis A, B, C, E
Syphilis
HIV-1 and HIV-2
Entamoeba histolytica
Complete blood cell count with differential
C-reactive protein and erythrocyte sedimentation rate
Albumin
Urea, creatinine, and electrolytes
Aminotransferases, bilirubin, gamma-glutamyltransferase, alkaline phosphatase
Human T-lymphotropic virus types I and II antibodies
Stool testing
Clostridium difficile toxin polymerase chain reaction
Fecal microscopy/culture/sensitivity with routine bacterial culture for enteric pathogens
Fecal Giardia antigen
Fecal Cryptosporidium antigen
Fecal ova/cysts/parasites (including B. hominis and D. fragilis)
Norovirus/Rotavirus enzyme immunoassay
Calprotectin
Fecal occult blood testing
Abbreviation: HIV: human immunodeficiency virus.

systemic review and meta-analysis study showed that the
lower GI route had higher clinical resolution rates than the
upper GI route in CDI patients.25 Moreover, Kao et al.
demonstrated that FMT via oral capsules had comparable
outcomes to delivery by colonoscopy in prevention of
recurrent CDI.68 Another key point to remember, FMT may
occur as a one-time therapy or with multiple intensive
doses, and it is based on the condition of the patient,
including the patient’s response to the treatment and the
efficacy of the therapy.69 In short, no current strong evi-
dence of the optimal FMT delivery method has been proven
in clinical practice, and the decision of the appropriate
method should depend on the individual clinical situation.
The schematic diagram of FMT process is shown as Fig. 1.
Patients monitoring and safety issues
Until now, the long-term outcomes of FMT have not been
completely comprehended. Based on current evidence,
FMT is viewed as a generally safe therapeutic method with
few adverse effects. Even so, every recipient of FMT needs
to be informed about the potential risks before the pro-
cedure. Most clinical trials and systemic reviews presented
that some minor adverse events, such as abdominal
discomfort, diarrhea, constipation, and low-grade fever,
were transiently noted after FMT, and uncommon severe
side effects were often associated with the possible com-
plications of endoscopy and sedation.17,19,66,70,71 The most
common adverse events are described in Table 4.47,52
Moreover, some case reports and cohort studies showed
that small populations of patients experienced IBD flares
after FMT.72e74 The definite mechanism of IBD flare after
FMT is still unclear, although Quera et al. suggested that
transient bacteremia may result in altered intestinal
permeability, resulting in a flare.74 Some experts are con-
cerned that there may be a greater risk for infection
following FMT in immunocompromised patients. A multi-
center, retrospective study examined FMT in 80 immuno-
compromised patients of CDI. There were not only absent
infection events related to FMT occurring, but also high
cure rates of 78% following a single FMT.11 Between the
different FMT delivery methods, there were no observed
differences in the proportion of adverse events.57,58,68
However, long-term immunologic effects of FMT is
another concern, but very little relevant information is
available. Several case reports have indicated that there
might be some undetermined link between FMT and certain
conditions, including peripheral neuropathy, idiopathic
thrombocytopenic purpura, Sjögren’s syndrome, and rheu-
matoid arthritis.17 Currently, the definite periodicity and
length of follow-up after FMT for monitoring of long-term
adverse events are not established. The European
consensus proposed that the follow-up period after FMT in
CDI patients should be at least 8 weeks, and the contents of
follow-up must include clinical and analytical data.49
Regulation
Regulation of FMT is an increasingly urgent requirement due
to the rapidly generating remarkable interest in this field.
There are vastly different regulations for FMT worldwide.
US FDA has approved that FMT is composed of a biological
product and a drug applied to diagnose, ease, treat, or
prevent disease or influence the structure or function of
the body.26 Health Canada regards FMT as a “New Biologic
Drug” and declares that all clinical studies must pass the
process of a clinical trial application to ensure it meets
quality and safety standards.75 In the United Kingdom, FMT

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6 J.-W. Wang et al.

Fig. 1 The schematic diagram of fecal microbiota transplantation process.

is also approved for treating CDI, and it is considered safe
and effective.14 From a clinical and research perspective,
any FMT application beyond treating CDI is deemed “off-
label”; therefore, the benefits and risks of clinical practice
must be carefully considered.52 In addition to the legal
regulation, another essential focus is to clearly explain
benefits, risks, process, and follow-up, and informed con-
sent for FMT should be provided to all patients before the
procedure.52,76
Challenges and future considerations
In spite of the clinically evident effectiveness and safety of
FMT, clinician and researchers are compelled to find sub-
stitutes for FMT owing to the risk of disease transmission
between the donor and recipient, patients’ acceptance,
undesirable outcomes, and the uncertain impacts on the
recipient’s immune system. Aside from standardization of
donor screening and clear protocols for adverse events
monitoring, a FMT registry should be set up to collect long-
term data and follow-up outcomes and complications.
Furthermore, we have gained much knowledge about the
bacterial population in the human intestine over the last
few years; however, little is known about the viral or fungal
composition in the gut and even the function of intestinal
bacteria. Additionally, another uncertainty of FMT is the
highly dynamic composition of live microbiota, which is
sensitive to external factors such as diet and drugs.6
Accordingly, future research should focus on identifying
the gut microbiota, defining their function, and further
manipulating the gut microbiota more precisely. In the

Table 4 Adverse events of fecal microbiota transplantation.

Minor
Abdominal discomfort
Bloating
Flatulence
Diarrhea/Constipation
Borborygmus
Nausea/Vomiting (particularly with oral FMT route)
Transient fever
Serious
Complications of endoscopy (perforation, bleeding)
Adverse effects related to sedation (aspiration)
Transmission of enteric pathogens
Peritonitis in a patient undergoing peritoneal dialysis
Pneumonia
IBD flares
Infection and/or sepsis (infection may be a long-term sequelae)
Post-infectious irritable bowel syndrome
Potential
Transmission of unrecognized infectious agents that cause illness years later (e.g., hepatitis C, HIV)
Induction of chronic diseases based on alterations in the gut microbiota (e.g., obesity, diabetes, atherosclerosis, IBD, colon
cancer, nonalcoholic fatty liver disease, IBS, asthma, autism)
Abbreviations: FMT: fecal material transplantation, HIV: human immunodeficiency virus, IBD: Inflammatory bowel disease.

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Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.011
 + MODEL
Fecal microbiota transplantation
years to come, we will look forward to personalized FMT for
different patients and conditions according to varied host
and disease genotypes/phenotypes.
Conflicts of interest
None.
Acknowledgments
This work was supported by grants from the Kaohsiung
Municipal Ta-Tung Hospital, Taiwan (KMTTH-106-028),
Kaohsiung Medical University Hospital, Taiwan (KMUH106-
6R02), and Ministry of Health and Welfare, Taiwan
(MOHW106-TDU-B-212-113006).
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