key: cord-0945792-kiavd58r
authors: Liu, Yanghua; Alnababtah, Kal; Cook, Simon; Yu, Ying
title: Healthcare providers’ perception of faecal microbiota transplantation with clostridium difficile infection and inflammatory bowel disease: a quantitative systematic review
date: 2021-09-20
journal: Therap Adv Gastroenterol
DOI: 10.1177/17562848211042679
sha: f150e99ad819235ab5a612e09d343bee69ffb4c2
doc_id: 945792
cord_uid: kiavd58r

BACKGROUND: Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are global gastroenterological diseases that cause considerable burden on human health, healthcare systems, and society. Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides Difficile Infection (rCDI) and a promising therapy for IBD. However, indication for FMT in IBD is still unofficial. Consequently, the National Institute for Health and Care Excellence (NICE) is seeking healthcare providers’ advice on whether to update FMT guidelines. METHODS: A systematic review methodology was adopted for this study. Five databases (CINAHL, MEDLINE, Cochrane Library, Scopus, Web of Science) and grey literature were systematically searched for English language literature to 14 May 2021. The quality of the included studies was then appraised using the Institute for Public Health Sciences cross-sectional studies tool, after which the findings of the studies were narratively synthesised. RESULTS: Thirteen cross-sectional studies with 4110 validated questionnaire responses were included. Narrative synthesis found that 39.43% of respondents were familiar with FMT (N = 3746, 95%CI = 37.87%–41%), 58.81% of respondents would recommend FMT to their patients (N = 1141, 95%CI = 55.95%–61.67%), 66.67% of respondents considered lack of clinical evidence was the greatest concern regarding FMT (N = 1941, 95%CI = 64.57%–68.77%), and 40.43% respondents would not implement FMT due to concerns about infection transmission (N = 1128, 95%CI = 37.57%–43.29%). CONCLUSION: Healthcare providers’ knowledge of FMT is relatively low and education is an effective strategy to improve it. As knowledge of FMT increases, willingness to recommend it also increases. Strengthening FMT clinical efficacy and reducing infection can enhance its public acceptance, application and popularity. However, further research is required to explore the donor screening procedure.

disease in the 21st century due to the changing diets that accompany industrialising societies. 5 The pathogenesis and clinical course of IBD are directly influenced by diet and the higher animal-sourced and higher calorie intake characteristics of Western diets may have negative effects on gut microbiota. 6 IBD includes two chronic inflammation diseases into the gut: ulcerative colitis (UC) and Crohn's disease. 7 Currently, there are up to 300,000 patients suffering from IBD in the United Kingdom, an estimated 3.1 million in the United Studies, and about 350,000 from 2005 to 2014 in China. [8] [9] [10] CDI is more common in patients with IBD, which can lead to higher recurrence, worse disease course, longer hospitalisation, diarrhoea, and higher rates of colectomy and mortality. 11, 12 A review reported that the CDI directly caused mortality rate is estimated at 5%, while deaths associated with its complications stands at 15% to 25%. 13 Faecal Microbiota Transformation (FMT) has been attracting increasing interest as a treatment for CDI and IBD in recent years. FMT involves taking faeces from healthy donors to rebuild the gut microbiota of a diseased individual, [14] [15] [16] and has shown to be an efficient alternative therapy for recurrent CDI (rCDI) 17 and a potential treatment for IBD. 18, 19 Even though FMT has wideranging therapeutic potential, how precisely it works is still poorly understood. 20 As such, the use of FMT is lower than the interest in it. A survey undertaken in the UK revealed that only 22% of physicians reported FMT utilisation in their institution in the last 10 years, while only 6% reported performing over ten FMTs. 21 The perception of FMT as a treatment is also a key factor in its utilisation. From a patient perspective, a survey revealed that approximately 46% of patients with UC were prone to accept FMT as a treatment, and up to 94% of patients with rCDI were willing to accept FMT if it was recommended by physicians. 22 Likewise, another survey showed that although patients found FMT unappealing, > 81% were open to it and this number increased to 94% when advised by their physicians. 23 Consequently, healthcare providers and their perception towards FMT are very important and directly influence patients' acceptance of FMT. Therefore, the purpose of this systematic review is to analyse and synthesise contemporary evidence about the healthcare providers' perception of FMT for CDI and IBD.

This systematic review aims to explore healthcare providers' perception of FMT for CDI and IBD. This will be achieved through identifying, critically appraising and synthesising all available research that answers the following question:

• What are the knowledge and attitudes of healthcare providers regarding FMT for CDI and IBD?

To identify primary studies, CINAHL, MEDLINE, Cochrane Library, Scopus, Web of Science, Google Scholar and grey literature were searched. The search strategy was conducted by two authors independently (YL, KA). The following search terms were utilised: ["healthcare professional" OR "healthcare giver" OR "healthcare provider" OR "healthcare worker" OR "physician" OR "medical staff" OR "doctor" OR "nurse" OR "medical student" OR "healthcare personnel"] AND ["perception of FMT" OR "attitudes of FMT" OR "recognition of FMT" OR "awareness of FMT"]. Due to FMT being a novel treatment in recent years and a limited number of studies focusing on this topic, no date limitation was applied to the search, with all studies published up until the latest search date (14 May 2021) being considered.

Physicians, nurses, medical students, or associated health professions in any kind of healthcare settings globally were included in this systematic review.

Different types of studies were included if they were primary research and focused on healthcare providers' perception of FMT for CDI, rCDI, IBD, UC, Crohn's disease or CDI and IBD. However, other related gut microbial dysbiosis disease using FMT were excluded. Any reviews, editorials, letters, perspectives, commentaries, reports, and studies with insufficient related data were excluded as well.

journals.sagepub.com/home/tag 3

Two researchers (YL and KA) independently extracted data into a data extraction template which was pilot tested with two included papers. The authors extracted data after quality assessment to save time and reduce potential selection bias. 24 Any disagreements were discussed by the two researchers to reach a consensus and the other two authors were consulted if necessary. The researchers extracted data from each included study as follows: title, the first author, publication year, type of study design, setting, country, the approaches of data collection and analysis, targeted population, the number of participants included in the survey or questionnaires, healthcare providers' knowledge and attitudes towards FMT.

The selection process was guided by the PRISMA flow diagram shown in Figure 1 . All included studies were selected by following the three-stage screening process; the authors browsed and appraised the titles after removing duplicated studies from different databases; abstracts were assessed to double-check the qualification of those included by title and finally a full-text assessment was implemented to guarantee all inclusion criteria were completely satisfied. The whole process was undertaken with the assistance of Endnote software, which is recommended by Bramer and colleagues. 25 The authors YL and YY implemented and recorded the above process, and shared the record with the other authors for confirmation. Disagreements were discussed and solved by consensus.

Although an interest in perceptions may generally fall within the realm of qualitative research, the literature on FMT for CDI and IBD has exclusively explored this question through quantitative approaches so far, specifically through cross-sectional studies. Quality assessment of these studies was independently carried out by the authors YL and KA who used the quality assessment tool from the Institute for Public Health Sciences. 27 This is widely used for appraising descriptive/cross-sectional studies and is suitable for the questionnaire methods employed in the included studies. The other authors were consulted to resolve any discrepancies or disagreements in this process.

A narrative synthesis was conducted in this review due to the diversity in the participants' recruitment, different methodologies and statistical heterogeneity. To conduct the narrative synthesis the present researchers followed four main steps. 28 First, the authors organised results in a data extraction table (see Supplemental Appendix 1). Following that, the authors created a theming table to illustrate how themes were generated. The next step was to list results and chunk results into distinct sections. Finally, the authors labelled each section as a category and used categories to discuss results in the review. Through this approach, the present researchers integrated different studies to generate new understandings around healthcare providers' perceptions of FMT for CDI and IBD rather than simply summarising pre-existing research. This contributed to the high-quality of this research while any discrepancies were discussed to reach consensus among the authors.

Thirteen quantitative studies were included in this review for analysis, which are detailed in Table 1 alongside their bibliographic details and narrative outcomes.

Languages, publication dates and countries. All included studies were in English and published between 2013 and 2020. Three studies were carried out in China and another 10 studies were conducted in other countries spanning Europe, North America, Jordan, Australia and Asia as shown in Table 1 .

Study design, participants, questionnaires' design and quality of included studies. All thirteen included studies were cross-sectional studies; four studies were conducted via field survey, while another nine studies were carried out via the Internet or e-mail. As shown in Table 1 , the targeted population was varied among the included studies, six studies focused on physicians, two studies focused on gastroenterologists, one study focused on healthcare providers, one study focused on clinicians (clinicians are all healthcare providers who directly treat patients, while physicians are clinicians who focus in a particular specialty involving non-surgical treatment), one study focused on registered nurses, two studies focused on medical students. All these participants could be classified as healthcare providers. A total of 9171 baseline questionnaires were distributed, while 4110 valid questionnaires were returned with an overall return rate of 44.82% and the range for the return rate of questionnaires was from 5.36% to 98.16%.

Due to there being no validated survey instruments assessing healthcare providers' perception regarding FMT available, seven studies used selfdesigned questionnaires. Another two studies' questionnaires were adapted from Ma and colleagues because they had similar research objectives, but there was no information about the questionnaire design in another four studies. However, among thirteen included studies, only three studies pilot tested their questionnaires before distribution, while another ten studies did not describe whether they tested their questionnaires before distribution. The present authors used the 11 questions included in the Institute for Public Health Sciences tool to appraise the quality of included studies; the detailed questions are presented in Table 2 and the quality assessment of each included study is shown in Figure 2 .

The answer to Q1 and Q2 among all the included studies were Yes (see Figure 2 ), thus, according to Institute for Public Health Sciences, it was 42% respondents reported a lack of evidence was the most commonly cited concern (95%CI = 28.58%-55.42%).

25% respondents agreed that there was a significant infection risk from donor stool despite screening (95%CI = 13.23%-36.77%).

12% respondents considered infection risk as their greatest concern towards FMT (95%CI = 0-20.83%).

Porter worth proceeding with the remaining questions. Q3 assessed the selection bias of each study, which could be evaluated by assessing the sample. Q4 checked the measurement bias and it could be assessed by whether the researchers used subjective or validated measurements in the studies. Q5 assessed whether the researchers collected data in a correct and justified way. Q6 aimed to explore whether the result of each included study was precise. Q7 regarded how results were presented in each study, which will be assessed in the results section. Q8 was about the studies' analysis process and whether in-depth description was provided or whether there was insufficient data to support the findings. Q9 focused on whether the researchers offered adequate discussion of the evidence and the reliability of their findings. Q10 aimed to explore the applicability of the research, which was considered through examining the similarities between research subjects and contexts to other settings. The last question was about the contribution of the studies. As Figure 2 shows, the overall quality of the included studies was assessed as 'good'. The main issues among the included studies were selection and measurement bias. Future studies would not only benefit from larger sample sizes and the validation of questionnaires to enhance reliability and generalisation, but also employing qualitative research approaches to understand perceptions in more depth.

Results and synthesis Familiarity with FMT. Nine studies mentioned this topic, and the detailed description is presented in Differences in theoretical and practical focus between medical students and physicians may be causing the differences in their readiness to recommend FMT, however more certain reasons would need to be explored in future studies.

Greatest concerns regarding FMT. Nine included studies assessed the greatest concerns regarding FMT from healthcare providers' perspectives. Each included study used percentages to narrow down the greatest concerns and apply descriptive statistics to analyse data. Three out of nine included studies reported that the greatest concern regarding FMT was lacking clinical evidence to support its safety. However, Dennis and colleagues reported that they would not refer FT due to not knowing where to access FT, whose conclusion was similar to Zipursky and colleagues's study. It is likely that access and knowledge of accessing FT have improved since these early studies as interest in FMT has grown. Compared with the previous five studies, Ma and colleagues pointed out that high expectations from patients and pressure on clinical efficacy were the greatest concerns towards FMT from Chinese clinicians. Ren and colleagues stated that acceptability to patients (79.2%) was the major concern of FMT from Chinese physicians' perspective. Similarly, another study carried out by Wu and colleagues also reported that 36.71% of Chinese medical students did not support FMT due to lack of analysis of patients' willingness or cost-effectiveness. The findings from these studies suggest that patients' perceptions and expectations regarding FMT are significantly important for its application and popularity in China, while the clinical efficacy and appropriate clinical situation of FMT is relatively more important in other countries. However, further research needs to be conducted to confirm this suggestion.

Donor screening procedures. In total six included studies and 3176 participants responded to the donor screening procedure; however, their perspectives were different. Two studies referred to FMT banks and emphasised the consent of donors, and two studies showed their concerns regarding the infection risk from donor stool. Compared with the above perspectives, 30.7% of Iranian physicians assumed that stool preparation was the most unappealing aspect of FMT. Chinese physicians preferred donors who had a similar microbiota environment to the recipient, and 73.69% Chinese postgraduate medical students were willing to donate their faeces.

Causing the transmission of infection. From the data in Table 1 , it is apparent that the overall level of 40.43% of respondents would not implement FMT due to infection concerns. This varied between professions, however: 33.42% of doctors, 41.96% of nurses and 69% of medical students would not implement FMT due to these concerns.

The purpose of the current review is to evaluate healthcare providers' perception of FMT with IBD and CDI. The thirteen included studies include perspectives from healthcare providers in eight different countries. Among them, six studies were conducted in developing countries, while seven studies were undertaken in developed countries. All major outcomes are illustrated in the summary of the findings table which is presented in Table 3 . The overall rate given in Table  3 was calculated by dividing the overall number of people responding the topic by the total number of valid respondents.

Contributions to the literature Familiarity with FMT. Despite the 7-year timerange of included studies, the results of the present review's consistently suggests that the overall level of familiarity with FMT among healthcare providers is low. One possible implication of this is that healthcare providers' familiarity with FMT has not changed much despite the various advances that have been made in FMT. Ren and colleagues found that geographical region was an essential factor impacting their knowledge of FMT and this was also evident in this review. This phenomenon may be caused by the dissimilarity of the economy, the frequency of information exchange and the unequal allocation of medical resources, which can impact public acceptance and the speed of spreading new knowledge and technology. 37 Meanwhile, this review also found that ethics and culture are important elements of the geography of healthcare providers' FMT knowledge as discussed later.

Furthermore, healthcare providers' familiarity with FMT may positively influence their willingness to perform it. As found in other studies, Sofi and colleagues 41 reported that the lack of knowledge of FMT was the principal reason for their respondents not considering FMT. However, the familiarity with FMT does not guarantee healthcare providers are willing to experience it. Zipursky and colleagues argued that 100% of respondents in their survey treated rCDI, but only 20% chose FMT. This is similar to another study who reported that 40% of physicians had heard of FMT but were reluctant to try it. 42 More surprisingly, a survey conducted by Stevenson revealed that registered nurses' knowledge and perception of FMT were irrelevant to their age, education, years of experience and practice setting.

However, compared with Stevenson's finding, Ren and colleagues found that age, educational level, professional title, practice setting and working experience could influence physicians' knowledge. Similarly, Wu and colleagues reported that gender, speciality, university and health status can also affect postgraduate medical students' recognition level of FMT. However, other included studies did not analyse whether these confounding factors influenced the targeted population's knowledge. Consequently, it is difficult to draw a conclusion from current evidence of whether there is a relationship between healthcare providers' knowledge and these variants. Overall, healthcare providers have poor health literacy towards FMT, thus, it is urgent to improve their knowledge in the future.

This review suggests that healthcare providers' knowledge directly influences their attitudes towards FMT. Compared with other countries, Iranian physicians have the highest-level knowledge of FMT and their readiness to recommend it to patients is relatively higher. The most likely cause of this phenomenon was educational monthly seminars which were held by the Iranian Association of Gastroenterologists and Hepatologists. 35 Similarly, Wu and colleagues reported that Nanjing Medical University students have the highest rate of familiarity with FMT in this review, possibly due to the leading FMT centre and the Chinese FMT Bank being supported by this university. Thus, compared with other medical students, they may have more chance and medical resources to understand FMT. This also can explain why students in this university are more willing to donate faeces. Interestingly, Madar and colleagues indicated that low familiarity with FMT of Romania medical students owed to inadequate exposure through lack of lectures focusing on FMT. Consequently, education would appear to be an effective strategy to improve healthcare providers' knowledge and attitudes towards FMT.

By contrast, Jordanian healthcare providers have the lowest familiarity with FMT and the most negative attitudes towards it. Two possible 29 Most people in Jordan are Muslim; it is significantly important to obey the religious commitment to halal non-alcoholic foods and beverages. 29 Likewise, Ontario physicians shared similar attitudes towards FMT and 76% respondents would not recommend it to patients, the most common reason being insufficient awareness of where to access the treatment. 30 Similarly, Zipursky and colleagues found that 65% respondents had not recommended FMT due to lacking the right clinical situation to perform FMT, which is in accordance with Dennis and colleagues. These results would seem to suggest that healthcare providers' readiness to recommend FMT to patients may improve with their knowledge of FMT increasing and FMT's wider application.

Meanwhile, the unpleasant nature of FMT is another barrier for healthcare providers in recommending it to their patients. 30, 40, 41 However, according to Brandt, physicians' reluctance to recommend FMT to patients is due to the inadequate number of randomised controlled trials to demonstrate its efficacy and safety. 43 This is congruent with Xu and colleagues who reported that clinical effectiveness is a significantly important factor to determine patients' positive attitudes regarding FMT and physicians' readiness to recommend it. 44 However, a growing body of evidence has reported the safety and effectiveness of FMT. A study by Hota and Poutanen 45 showed that FMT was an effective treatment to rCDI, and multiple FMT could achieve better patient outcomes than single FMT. Similarly, a prospective real-world study by Kelly and colleagues also suggested that FMT was highly effective and secure for CDI, 46 which was consistent with the conclusion from a systematic review by Moayyedi and colleagues. 47 Furthermore, a cohort study reported that the overall cure rate of CDI was high and most IBD patients acquired clinical improvement after FMT, and they found no severe adverse events directly contributed to FMT. 48 Meanwhile, a case report suggested that FMT could effectively improve Crohn's colitis patients' clinical, endoscopic, and histological symptom, 49 while FMT could also be significantly effective for active UC patients. 50 Similarly, Paramsothy and colleagues indicated that 90% of Australian gastroenterologists would recommend FMT to CDI patients, while 37% for UC and 13% for CD patients. Furthermore, a national survey conducted by Mcilroy and colleagues reported that 38% respondents had implemented FMT on CDI patients, while 34% would consider utilising FMT on IBD patients. It could be concluded that healthcare providers' perception towards FMT may change with increased evidence to support its safety and efficacy in CDI and IBD. However, not all of this evidence was available when the studies included in this review surveyed their participants, and therefore, may not have impacted on the perceptions reported here.

In conclusion, it seems that the limited knowledge, insufficient practising experience, unappealing nature of FMT and clinical efficacy may directly impact healthcare providers' readiness to recommend it. It also appears that healthcare providers' readiness to recommend would improve with their knowledge increasing and FMT's wider implication. Meanwhile, this review also suggests that ethical and cultural factors also need to be considered and the most effective educational style for enhancing FMT knowledge needs to be explored in the future.

Greatest concerns regarding FMT. Clinical efficacy and safety of FMT are the leading concerns among healthcare providers in this review, whose conclusion was consistent with the statement in the NICE's 2021 guideline. 51 Several factors play a role in determining this phenomenon. First, FMT is a novel therapy that is short of substantial clinical evidence to demonstrate its safety and effectiveness with the related disease, and only rCDI was written into the NICE's 2014 guideline. 39 Second, no worldwide and standardised FMT procedure is available, including donor selection, laboratory preparation and delivery approaches. 33, 39 However, a prospective surveybased study revealed that FMT was safe for longterm rCDI. 52 With efficacy varying with indication, healthcare providers' perception may also vary based on indications. Consequently, 12 journals.sagepub.com/home/tag future research should focus more on exploring FMT's safety and effectiveness, and standard treatment protocols also need to be developed.

However, apart from the clinical effectiveness and safety of FMT, patients' acceptability is another most common consideration for the therapeutic application of FMT. The possible reasons are the 'yuck factor' or the cleanliness/hygiene of the faecal matter. 22, 30, 32 Consequently, to enhance patients' acceptance, the FMT delivery route is essential. Compared with the upper GI tract, the lower GI tract is more acceptable by most patients. 22, 32 The upper GI route consists of gastroduodenoscopy, nasointestinal tube and oral capsule, while the lower GI route includes colonoscopy and retention enema. 37 To date, the optimal method is still unclear, but a systematic review reported that rCDI had a higher cure rate by FMT via colonoscopy than other routes. 53 Brandt and Aroniadis found that approximately 75% of FMT for patients with rCDI are conducted through the lower GI tract, while 25% through the upper GI tract. 54 Similarly, previous studies by Madar and colleagues and Paramsothy and colleagues revealed that colonoscopy was the most preferred routes for healthcare providers performing FMT. However, according to Chuong and colleagues, social stigma or concerns regarding facing stigma towards FMT is another factor which can impact its acceptance. 55 In such circumstance, social media should not exaggerate or underestimate the efficacy of FMT. 32 The conclusion can be drawn from these findings that enhancing social acceptance is crucial for FMT's future application.

Donor screening procedures. Due to there being no international regulatory or common legal framework regarding the donation of human faecal available, 56 different studies and guidelines hold different opinions towards FMT donor screening procedure. According to Ma and colleagues, FMT is more like blood donation rather than organ donation. Thus, different stool banks agreed that the pathogens included in the bloodscreening programme should be consistent with the screening procedure for blood donors. 57, 58 However, a recent consensus guideline released by Australian experts suggested that stool donors should be screened with a careful history together with blood and stool testing, and should test Multi Drug Resistant Organisms (MDROs) as well. 59 In addition, healthcare providers should also consider religion, culture and diets in donor screening processes. This argument is supported by Al-Bakri and colleagues and Bokek-Cohen and Ravitsky. 61 Islam is the predominant religion in Jordan, 29 and Muslim patients might have a strong prohibition to receive a faecal transplant from non-Muslim donors. 32 Similarly, kosher requirements for some Jews and vegetarian requirements for some Buddhists or Hindus may need consideration. 61 This phenomenon may result from recipients considering FMT as the ingestion of a derivative of food which they consider as forbidden, thus they may have a strong emotional rejection to receive a sample from these donors. 61 Although consent is a standard of care for FMT in most centres, healthcare providers should consider such religious or cultural factors when obtaining consent from recipients before performing FMT, especially the samples from unknown donors.

A recent international consensus conference reported that stool banks may offer trustworthy, timely and equal access to FMT for patients and a traceable procedure which can guarantee its safety and quality. 62 However, ethical issues regarding stool donors should also be given further consideration, including informed consent guidelines for stool banks and the privacy of stool donors. 63 To recruit and retain more donors, the organisers should motivate and express gratitude journals.sagepub.com/home/tag 13 to them, and highlight their positive influence on FMT research. 63 Therefore, healthcare providers should consider the challenges and concerns with stool banks when conducting FMT.

Nonetheless, in terms of the donor screening criteria, it should comply with the national regulatory guidelines or follow the most updated international expert consensus. 56 To select a healthy, stable and diverse faecal microbiota donor, age, weight criteria, healthy lifestyle and no antibiotic use within a certain period before donation should be considered as well. 56 Cammarota and colleagues hold a similar viewpoint which was presented in the European consensus conference, in which they summarised the donor selection procedure. In the preliminary stage, donors' medical history, lifestyle habits, age and medication history should be considered, while on the day of donation, donors' recent history, risk factors of selected and their laboratory outcomes also need to be checked. 57 In summary, the current evidence suggests that age, medical history, religion and cultural background, lifestyle habits, medication history, informed consent, and clinical testing (e.g. MDROs) should be taken into consideration when developing the donor screening procedure.

Causing the transmission of infection. As presented in this review, infection is one of the most common concerns regarding side effects of FMT, yet, the perceived risk may outstrip actual risk here; FMT seemed safe and the rate of infection transmission was low. 52, 64 However, there are other side effects as well, including physical detrimental events (e.g. fever and abdominal disorder) 64 and mental illness (anxiety and depression). 65, 66 Therefore, strict donor screening is an effective strategy to reduce this potential risk. However, Dennis and colleagues found that no physicians agreed that FMT could cause transmission of infection. This phenomenon may have been attributed to many hospitals in Canada having not performed FMT and this study having been carried out before publication of a randomised controlled trial (RCT) on FMT, thus Ontario physicians could not predict the side effects of FMT. It seems possible that over time, healthcare providers have become more concerned about the transmission of infection with FMT.

Apart from stricter donor screening, exploring a standardised procedure of collection, preparation and storage of faecal samples is also significantly important to reduce infection. In terms of the faecal sample, faeces should preferably be collected in a specific single-use container in the stool bank. 62 Meanwhile, to guarantee the quality, faecal samples should be manipulated and stored within 6 hours after defaecation in the stool bank. 62 Furthermore, every faecal sample is marked with a unique bar code to provide efficient donor-recipient trace back. 67 Finally, to assess potential infection after FMT, Gliklich and colleagues indicated that prospective registries recruiting large cohorts of recipients with long-term follow-up are the only practical approach to achieve this purpose. 68 In summary, effectively controlling possible infection is essential to ensure FMT safety and enhance patients' satisfaction in clinical practice.

In conclusion, this section has discussed that healthcare providers' knowledge and attitudes can be improved through education, while stricter donor screening procedures can effectively prevent infection and enhance clinical safety. Most patients experienced diarrhoea and constipation in the short-term follow-up after FMT, while 13% had gastrointestinal discomfort, 10% weight gain, and 11.8% new infections (all considered irrelevant to FMT) in the long-term follow-up. 52 Therefore, as a novel and promising therapy, more research is required to examine the longterm efficacy and safety of FMT.

Several limitations exist in the present review. First, due to time and language limitations, the authors only extracted data from studies published in English which may lead to language bias. Second, although the authors attempted to search as many as papers through several different databases, grey literature and manual searching, there was no qualitative evidence that focused on this review topic and the existing evidence was limited. Third, the small number of studies is also limits our evaluation of factors which may affect healthcare providers' perceptions. The main reason for this phenomenon may contribute to FMT being underused present and most studies only focusing on exploring its long-term efficacy and safety. Thus, few studies pay attention to the topic of this review. Finally, the questionnaires used in the included studies were varied, thus outcomes were heterogeneous and conducting meta-analysis was not suitable. All these weaknesses may impact the robustness of the review outcomes. Consequently, in the future, it is necessary to conduct qualitative research to explore this topic in greater depth, which could be useful in understanding these issues more deeply, and also create an internationally recognised and validated questionnaire on this topic.

This report was the first systematic review that focused on healthcare providers' perception and attitudes towards FMT with CDI and IBD, whose outcomes were valuable for FMT application and popularity, and have highlighted various avenues for future FMT research more widely. Through a comprehensive literature search, the critical appraisal of included studies, data extraction and narrative synthesis, five major outcomes were synthesised from thirteen cross-sectional studies to achieve the objective of this review. The familiarity with FMT and healthcare providers' readiness to recommend it could provide insight into their knowledge and attitudes of FMT with CDI and IBD, while donor screening procedures, greatest concerns regarding FMT and its potential transmission of infection could provide useful information towards the further improvements for FMT in the future.

We found that the overall level of healthcare providers' knowledge towards FMT is still low, while education may be an effective strategy to improve it. To enhance their recognition of FMT, strengthening the professional training of FMT together with positive portrayal within mainstream media may have a positive effect. In terms of educating medical students, medical lectures, classroom teaching and social media are effective ways. However, the mass media and mainstream media should neither exaggerate nor underestimate the function of FMT, which may mislead the public.

Over time, readiness to recommend FMT seems to have increased, which may be a result of increasing interest, evidence and guidelines surrounding its use. However, to enhance healthcare providers' willingness to recommend FMT, apart from increasing their knowledge and practising experience, optimising stool preparation and reinforcing FMT clinical efficacy, ethics and cultural components also need to be considered. Furthermore, knowledge had a positive influence on healthcare providers' attitudes towards FMT. The evidence from this review implies that education is the best strategy to improve healthcare providers' knowledge and willingness to recommend FMT, thus future practice should be taken into consideration to explore the most effective education time and methods.

This review demonstrates that clinical efficacy and safety are still the most significant concerns for healthcare providers. Therefore, future practice should focus on seeking a larger sample size RCT to demonstrate FMT's long-term efficacy and safety. This review has found concerns about infection transmission, while strict donor screening procedures are crucial to reducing this risk. Despite different healthcare providers holding different perspectives towards donor screening procedures, an increasing number of experts have reached the consensus of testing MDROs in donor screening which can provide some valuable information for future research. However, healthcare providers should also consider donors' age, medical history, religion and cultural background, lifestyle habits, medication history, informed consent, and clinical testing. In summary, future practice should emphasise investigating an international standard donor screening procedure.

In conclusion, as a novel treatment, FMT has a long way to proceed to achieve wide application and popularity. The most urgent strategies include improving healthcare providers' knowledge, demonstrating its long-term efficacy and safety, and designing an international standard donor screening procedure.

Kal Alnababtah and Yanghua Liu designed the study. Yanghua Liu drafted the manuscript; Ying Yu, Kal Alnababtah and Simon Cook were involved in the revision of the manuscript. Yongjian Zhou and Yong Lin provided professional consultation; Alice May offered language support. Yanghua Liu and Helen Ryba were responsible for literature retrieval. Kal Alnababtah supervised data collection and analysis. All of the authors have read and approved the final version of this manuscript.

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The author(s) received financial support for the research, authorship, and/or publication of this article from

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The recognition and attitudes of postgraduate medical students toward fecal microbiota transplantation: a questionnaire study

Physician attitudes toward the use of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection

Physician outlook toward fecal microbiota transplantation in the treatment of Clostridium difficile infection

Barriers to greater utilization of fecal bacteriotherapy for chronic Clostridium difficile infection

Editorial commentary: fecal microbiota transplantation: patient and physician attitudes

Clinical efficacy maintains patients' positive attitudes toward fecal microbiota transplantation

Is a single fecal microbiota transplant a promising treatment for recurrent Clostridium difficile infection?

Fecal microbiota transplantation is highly effective in real-world practice: initial results from the FMT National Registry

Faecal microbiota transplantation for Clostridium difficile-associated diarrhoea: a systematic review of randomised controlled trials

Fecal microbiota transplantation is safe and efficacious for recurrent or refractory Clostridium difficile infection in patients with inflammatory bowel disease

Fecal microbiota transplantation inducing remission in Crohn's colitis and the associated changes in fecal microbial profile

Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial

Faecal microbiota transplant for recurrent or refractory Clostridioides difficile infection

Long-term safety of fecal microbiota transplantation for recurrent Clostridioides difficile infection

Duodenal infusion of donor feces for recurrent Clostridium difficile

An overview of fecal microbiota transplantation: techniques, indications, and outcomes

Media discourse on the social acceptability of fecal transplants

How do I establish a stool bank for fecal microbiota transplantation within the blood-and tissue transplant service?

European consensus conference on faecal microbiota transplantation in clinical practice

Challenges in fecal donor selection and screening for fecal microbiota transplantation: a review

Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice

Screening of faecal microbiota transplant donors during the COVID-19 outbreak: suggestions for urgent updates from an international expert panel

Cultural and personal considerations in informed consent for fecal microbiota transplantation

International consensus conference on stool banking for faecal microbiota transplantation in clinical practice

Ethical implications of recruiting universal stool donors for faecal microbiota transplantation

Monitoring fecal microbiota transplantation practice in a rapidly evolving health and regulatory environment

Unraveling the influence of gut microbes on the mind

Systematic review: faecal microbiota transplantation therapy for digestive and nondigestive disorders in adults and children

Registries for evaluating patient outcomes: a user's guide