Fecal Microbiota Transplantation Research over the Past Decade: Current Status and Trends

Background Fecal microbiota transplantation (FMT) is a current research hotspot, with a surge in the output of publications over the past decade. This study dedicates to the exploration of the research status and highlights significant themes and future trends in FMT research with the aid of bibliometric analysis. Methods FMT publications from 2012 to 2021 were retrieved on August 12, 2022, using the SCI-Expanded of Web of Science (WoS). The Bibliometrix in R program, Microsoft Office Excel, VOSviewer, and CiteSpace were utilized for bibliometrics and visual analysis, revealing the main publications, journals, countries, agencies, authors, and keywords distribution in FMT research. Results There were 2,931 papers included. FMT research presented a growing trend from 2012 to 2021. The countries with the most publications and contributions in FMT area were China and the United States. The high-yield institutions were Harvard University, Udice French Research Universities, and the University of California System. The primary authors were Nieuwdorp Max, Allegretti Jessica R, and Kassam Zain. Frontiers in Microbiology and Science were the top-ranked journals in publications and total citations, respectively. The important topics primarily included FMT-related mechanisms and the usage of FMT in Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), metabolic disease, neurological disorders, and psychiatric disorders. Future research would primarily concentrate on neurological disorders, chemotherapy and immunotherapy for malignant tumors, and FMT-related consensus and guidelines. Conclusion With the help of bibliometric analysis, we were able to obtain the understanding of the status and trends of global FMT-related research. The field of FMT is undergoing tremendous progress, and our findings can guide clinical researchers' and practitioners' future work in the rapidly evolving field of FMT.


Introduction
Fecal microbiota transplantation (FMT) means that the transfer of functional GM of healthy people into the intestine of patients to restore the balance of the patient's GM or rebuild the GM to study the causal relationship between GM and disease. FMT can even be traced back to ancient China [1]. In 1958, Eiseman et al. [2] frst reported that four patients with severe pseudomembranous colitis recovered after fecal enema, which is the origin of modern FMT research. In 1989, Bennet and Brinkman reported [3] the frst patient with ulcerative colitis (UC) treated with fecal enema. However, it was not until 2013 that the U.S. Food and Drug Administration classifed human feces as a drug, and FMT was frst included in the treatment guideline for CDI [4]. Since then, FMT research had developed rapidly. In the past decade, FMT-related research in recurrent CDI (rCDI) [5] and infammatory bowel disease (IBD) [6,7] has made signifcant progress. In addition, there are increasing applications of FMT in multiple other diseases, such as irritable bowel syndrome (IBS) [8], constipation [9], liver disease [10], cancer [11,12], diabetes [13], metabolic syndrome (MS) [14], autism [15], and neurological disorders [16].
Bibliometrics is a quantitative approach that employs mathematical and statistical strategies to assess the features of publications, enabling researchers to outline a complex graph of the knowledge structure and the development of specifc knowledge, and has obtained successful application types were limited to "article" and "review," (2) publication years were from 2012 to 2021, and (3) there was no language limit. All searches were completed and downloaded on August 12, 2022. A total of 2391 FMT-related papers were fnally obtained ( Figure 1). We extracted the key information from the raw data and saved it in TXTformat. Tese data do not relate to any personal information, so informed consent is not required. Te impact factors (IFs) and JCR partitions refer to "Journal Citation Reports ™ 2021." 2.2. Data Analysis. Te Bibliometrix R package (v 4.1.3 Windows, the R Foundation), VOSviewer (v 1.6.18, the Netherlands), CiteSpace (v 6.1.R3 Basic), and Ofce Excel 2019 (Microsoft, Washington, USA) were used in the analysis. Te Bibliometrix contains a set of tools undertaking quantitative research in scientometrics [23]. VOSviewer is widely used for bibliometric analysis due to its more beautiful visualization, especially keyword cooccurrence analysis [24]. CiteSpace is a visualization analysis software gradually developed for scientometrics. To aid comprehension of FMT research, each program provides for the creation and display of bibliometric networks. Tese tools specifcally examined the distribution of each analyzed component, including annual scientifc output, most relevant sources or authors or afliations, production and local impact of top journals and authors over time, country scientifc production and collaboration network, historical citation network, high-cited papers and references, common keywords, and cluster analysis.
Te number of papers (Np) can refect the author's scientifc productivity, and the analysis of the core authors can grasp the research trend and development trend of a certain feld. However, relying solely on the Np does not evaluate an author's outstanding contribution to FMT research, through a series of scientometric indicators such as total citation (TC) and H-index can further evaluate the author's contribution. Te TC is a useful index for determining the signifcance and efect of an author's cumulative papers and is used to assess a person's academic achievement. Te H-index was developed by American physicist Jorge E Hirsch to assess individual academic achievements, and it was then applied to assess the academic infuence of journals.

Results
From 2012 to 2021, total 2931 papers were obtained based on SCI-E of WoSCC. FMT-related papers were published in 875 journals by more than 15,000 authors from more than 3,000 institutions in 81 countries and regions, of which 1,940 were "articles" and 991 were "reviews." Te English literature accounted for 99.17% of the total Np. Figure 2 shows that the Np in FMT research was on the rise from 2012 to 2021, and the annual average Np is 293. Te Np increased slowly from 2012 to 2017. From 2018 to 2021, Te Np rose rapidly before peaking in 2021 (n � 774, 26.4%). A polynomial model (f(x) � p 0 x n + p 1 x n−1 + p 2 x n−2 + p 3 x n−3 + . . . + p n ) was created to predict the output in 2022, and the formula was y � 9.1553x 2 − 36847x + 4E + 07. Te year and the Np showed a statistically signifcant link (R 2 � 0.9862), and the goodness-of-ft was well. We predict that the Np on FMT would reach roughly 920 in 2022 based on the ftting curve. Table 1 shows the academic output of top 10 journals. Frontiers in Microbiology ranked frst in Np (n � 66), next were Gut Microbes (n � 62), World Journal of Gastroenterology (n � 52), PloS One (n � 45), and Microbiome (n � 44). Te TC and H-index indicate the importance of the journals. Table 2 lists the top 10 high-cited periodicals, among which Science (n � 9744) receiving the most citations, followed closely by Gastroenterology (n � 6522), Gut (n � 4339), Microbiome (n � 3361), and Nature (n � 3212). Moreover, Microbiome was at the top of H-index, followed by World Journal of Gastroenterology, Gastroenterology, Gut, Gut Microbes, and PloS One (Table 2). Figures 3(a) and 3(b) highlight the top 10 journals' yearly and cumulative output.

Main Journals.
Tese journals had the highest cumulative Np of 454, accounting for approximately 15.5% of total output, showing that they were the most prolifc.    close. Te annual issuances by high-yield countries are shown in Figure 4(b). Te Np in China was growing rapidly. In 2021, China surpassed the US to become the country with the largest Np. Figure 4(c) shows the annual production of the top 10 high-yield agencies. Te top 10 institutions produced articles every year between 2016 and 2021. Figure 4(d) illustrates the major funding organizations, mostly from the United States and China, demonstrating that these countries are highly supportive of FMT-related studies.    Notably, Allegretti Jessica R., Cammarota Giovanni, and Khanna Sahil had gradually increased their output in recent years and could publish more papers in the next few years.

Historical Cited Papers in FMT.
By the aid of the historically cited papers analysis in the Bibliometrix, some classic FMT-related papers were found ( Figure 5). To examine their research signifcance, two indicators, LCS (local citation score in the current dataset) and GCS (global citation score in the WoSCC database), were used. Te classical papers were published in 2012-2017 ( Figure 5 depicts the citation network). In 2012, a multicenter follow-up study [25] showed prolonged efcacy of colonoscopic FMTfor rCDI. A clinical study [26] summarized standardized frozen preparation for FMT in rCDI treatment, marking the transition of FMT research to standardization. Moreover, a study found that after the infusion of microbes from lean donors, the insulin sensitivity of recipients increased, demonstrating the favorable efect of reconstituted GM on metabolic syndrome [27]. A review outlined the use of FMT in CDI and its promise in other GM dysfunction-related diseases [28]. In 2013, a paper, with the highest LCS and GCS, showed that infusion of donor stool was a potential therapeutic strategy for rCDI, which was the frst controlled clinical study of FMT in treating rCDI-related diarrhea [5]. A meta-analysis further confrmed that FMT had good efcacy and safety in CDI [29]. In 2014, several randomized controlled trials (RCT) of FMT in CDI treatment were published [30][31][32], and the guideline for CDI treatment was updated, which strongly recommend FMT for multiple rCDI [33]. In 2015, a RCT further showed that FMT using colonoscopy-infused stool for rCDI was signifcantly superior to the vancomycin regimen [34]. Two clinical studies in Gastroenterology showed that FMT had good clinical effcacy and safety in individuals with ulcerative colitis (UC) [7,35]. A review outlined the indications, methods, and mechanisms of FMT [36].
In 2016, a RCT confrmed that frozen FMT was comparable to fresh FMT in treating diarrhea in adults with rCDI, suggesting that frozen FMT has potential clinical advantages [37]. Te other RCT in JAMA confrmed that FMT using donor stool by colonoscopy seemed safe and was more efective in preventing CDI fares than FMT with the patient's own feces [38]. In 2017, another RCT in JAMA comparing oral capsule versus colonoscopy FMT on rCDI confrmed that oral capsule was noninferior in preventing recurrent infection in adults with rCDI for colonoscopy FMT [39]. A meta-analysis showed that FMT was efective in recurrent and refractory CDI treatment, regardless of setup method or delivery route [40]. A well-designed RCT demonstrated that FMT can promote clinical remission and endoscopic amelioration in active UC and was linked with signifcant microbial alterations, which was a promising new treatment option for UC [6]. Moreover, European consensus on FMT-related clinical practice was published [41]. Te classic papers on FMT mainly focused on CDI and application reports other than CDI continued to emerge.

Top 20 High-Cited Papers in FMT.
Highly cited papers refer to the most infuential papers in the present dataset in Table 5. According to the ranking of TC, important papers can be quickly located. Te more citations, the higher the academic value of the paper, and new discoveries and trends can be found from the paper. Te papers with high TC are generally important discoveries or new interpretations, often reviews or signifcant original articles.
As shown in Table 6, FMT was mainly used in mechanism research and clinical research, mainly focusing on CDI, UC, MS, cardiovascular and cerebrovascular diseases, mental diseases, and cancer immunotherapy. (1) CDI: Surprisingly, in the top 20 most cited papers, only one is about FMT treatment of CDI. Te research showed that FMT was a potential therapeutic strategy for rCDI [5]. (2) UC: Two clinical studies have shown that FMT can provide relief in patients with active UC [7,35]. FMT from ACE2 mutant mice into germ-free (GF) mice could impart an increased propensity to develop severe colitis [42]. (3) MS: A 2012 study showed, after 6 weeks of infusion of lean donor microbiota, recipients had increased insulin sensitivity and butyrate-producing GM [27]. A 2015 study showed that jet  lag-induced dysbiosis can promote glucose intolerance and obesity, which can be transferred to GF mice after FMT [43]. Two articles published in Nature confrmed that artifcial sweeteners can cause glucose intolerance by modulating the GM [44], and dietary emulsifers can afect the GM in mice to promote colitis and metabolic syndrome [45], which were confrmed by FMT experiments. (4) Cardiovascular and cerebrovascular diseases: It was observed that hypertension can be transferred through FMT from hypertensive human donors to GF mice, demonstrating the direct efect of GM on host blood pressure [46]. Antibiotic-induced GM changes can reduce ischemic brain damage in mice, an efect that can    Table 5).
be transmitted through FMT [47]. (5) Mental diseases (MD): Colonization of the "depressed microbiota" from patients with major depressive disorder caused depression-like behaviors in GF mice compared to "healthy microbiota" colonization from healthy individuals [48]. A study showed that anhedonia and anxiety-like behaviors, as well as changes in tryptophan metabolism, were all generated in recipient animals by FMT from depressed patients into microbiotadepleted rats [49]. Te other study showed that FMT can alter GM and alleviate gastrointestinal and autism symptoms [15]. (6) Cancer immunotherapy: In 2015 and 2018, four studies showed that the drug resistant to immune checkpoint inhibitors (ICIs) was related to GM, notable changes in the GM between ICI responders and nonresponders were also noted, and FMT can enhance the antitumor efect of ICIs [50][51][52][53].

Most Local Cited References of FMT Research.
Local cited references refer to the most cited references in the present dataset. According to the ranking of TC, important references in the feld can be quickly located.
Checking the references can trace the development history of FMT, so we can have a more comprehensive understanding of FMT.    As shown in Table 7, we mainly reviewed the FMTrelated articles before 2012, and found that the research types were mainly case reports. In 1958, Eiseman et al. [2] reported that four patients with severe pseudomembranous colitis recovered after fecal bacterial transplantation, which was the origin of modern FMT research (refer to several FMT review articles). In 1981, a study showed that 16 patients with pseudomembranous enterocolitis received restoration of foral homeostasis by fecal enema [54]. In 1983, a case report in Lancet showed rectal infusion of homologous stool may cure recurrent Clostridium difcile enterocolitis [55]. In 1989, an article in Lancet showed that implantation of normal colonic fora treats UC [3]. Te other article reported the efect of bacteriotherapy on six patients with chronic recurrent Clostridium difcile diarrhea (rCDI-related diarrhea) [56]. Moreover, altering the GM could be a potential treatment for altering IBD and IBS [57]. In 2000, an article reported on the recurrent Clostridium difcile diarrhea treatment by direct administration of donated feces via colonoscopy [58]. In 2003, a case series reviewed the medical records of 18 subjects receiving donor feces via a nasogastric tube for rCDI and found favorable outcomes [59]. A case report showed that colonic infusion of donor feces could reverse UC in certain patients [60]. In 2004-2011, there were multiple case reports showing the potential role of FMT in CDI, which gradually attracted the attention of researchers. Simultaneously, some basic studies had shown that FMT can be used to study the mechanism of GM in disease occurrence [61,62]. Notably, FMT-related research had been in a slow development stage until 2012.

Evidence-Based Medicine Research.
Meta-analysis is used to compare and summarize the fndings of research on the same scientifc question based on statistical method. It is often used for quantitative combined analysis in systematic reviews. Table 8 lists the top 20 cited systematic reviews and meta-analyses in FMT, and we can fnd FMT-relatedmetaanalyses mainly focused on several aspects, including CDI, IBD, UC, IBS, and so on.
Te burst keywords can help us to know the evolutions and dynamics of hotspots, development trends, and frontier in a certain time. Figure 6(b) depicts the top 25 burst keywords. As we can see, in the early years, FMT for CDI and antibiotic-associated diarrhea was the main focus. Subsequently, the focus was mainly on the efects of FMT in IBD especially UC, diet-induced obesity, and clinical practice guideline of FMT. Overall, FMT-related research had undergone the stages from infectious disease to noninfectious disease, from case reports to RCT studies, and from empirical application to clinical consensus issued.

Cluster Analysis of Common Keywords.
Te cluster analysis is carried out based on cooccurrence keywords. Tis study uses hierarchical clustering to classify and merge the clustered keywords into a category, and proves the similarity of keywords in the feld of FMT. We analyzed all the included keywords through VOSviewer, showing a network diagram of cooccurrence relationships. Figure 7(a) shows the clustering analysis of common keywords (frequency set to 20), which was divided into fve types.

Cluster 1 (Red Topic).
Tis sort of keywords is principally related to the application of FMT in CDI. Major research topics include Clostridium difcile infection, antibiotic-associated diarrhea, diarrhea, clinical practice guidelines, risk factors, diagnosis, prevalence, prevention, and treatment. Cluster 2 (Green Topic). Tis sort of keywords is principally linked to the mechanisms of FMT and GM in health and disease, and involves many aspects such as immunity, metabolism, infammation, expression, oxidative stress, and barrier function. Cluster 3 (Light Blue Topic). Tis sort of keywords focused on FMT for neurological and psychiatric diseases. Major topics include Alzheimer's disease (AD), Parkinson's disease (PD), anxiety, depression, autism, stress, gut-brain axis, neuroinfammation, central nervous system, metabolome, and immune. Cluster 4 (Yellow Topic). Tis category is mainly linked to the application of FMT in metabolic syndrome. Major topics include obesity, insulin resistance, diabetes, fatty liver disease, cirrhosis, nonalcoholic steatohepatitis, Akkermansia muciniphila, chain fatty acids, bile acids, and glucagon-likepeptide-1. In addition, there was also the application of FMT in cancer, the main keywords include cancer, colorectal cancer, Fusobacterium nucleatum, immunotherapy, and chemotherapy. Cluster 5 (Deep Blue Topic). Tis category is mainly linked to the application of FMT in IBD and IBS. Major research topics include IBD, Crohn's disease, ulcerative colitis, IBS, butyrate-producing bacteria, and mucosaassociated microbiota.

Trends Analysis of Common
Keywords. Similar to concurrency graphs, overlay visual map in VOSviewer is a useful tool for forecasting future hotspots and trends in a variety of scientifc domains. As seen in Figure 7(b), the purple circles indicate the earlier keywords and the yellow represent keywords that have appeared recently. From 2012 to 2021, there are relatively unbalanced trends in the fve clusters, showing a tendency of diversifed development. Te trend in recent years (Figure 7(b)) shows that yellow nodes are mainly in the third and fourth cluster, and the main keywords include "Alzheimer's disease," "Parkinson's disease," " brain axis," "neuroinfammation," "chemotherapy," "immunotherapy," "consensus statement," and so on. Tese keywords mainly focus on neurological diseases and anticancer treatment.

Discussion
Bibliometric analysis can identify the characteristics of papers in specifc research areas, visualize the collaboration network between countries, institutions, and authors, show the citations and milestone articles, with unique advantages, and are widely used in various research felds. As a treatment method that has been written into the guidelines, FMT for CDI treatment has been applied in some countries, and the scope of its clinical indications has a trend of further expansion. To gain a better was in the stable and slow growth stage, which may be related to the fact that FMT was ofcially written into the clinical guidelines of CDI, indicating that FMT is beginning to be recognized by most investigators. 2017-2021 was a highyield period, and the Np in 2021 would reach its peak, indicating that FMT-related research is getting more and more attention, which may be due to the quick advancement of GM and FMT research, as well as rising researcher interest in FMT.
Few researchers know all relative journals in their feld, and researchers struggle to choose the most appropriate journals to output their research. Tis can be drawn from journal metrics obtained from the bibliometric analysis. From the source of papers, we found that most of the FMTrelated papers was mainly published in the specifc journals, such as Frontiers in Microbiology, Gut Microbes, and World Journal of Gastroenterology, which are world class journals and have greater impact on FMT research and ofer a publishing reference for FMT-related papers, and scholars may give priority to these journals. Frontiers in Microbiology ranked frst in Np, TC, and H-index, it is a renowned microbiology journal which advances our grasp of the role of microbes in addressing global challenges such as healthcare. Highly cited papers were mainly published in very wellknown medical journals, indicating that FMT-related research may represent medical cutting-edge research.
Most countries had participated in FMT research, of which the US and China had the highest Np, TC, and Hindex, and were at the center of global cooperation, showing their important contributions to FMT research, which was linked to their strong interest and backing on the microfora projects. In research institutions, Harvard University, University of California System and Harvard Medical School from the United States, and Udice French Research Universities and Inserm from France, as the top universities and institutions in the world, had published most papers. From prolifc authors, Nieuwdorp Max from the University of Amsterdam in the Netherlands had the highest Np, TC, and H-index, showing that his papers had a greater infuence on FMT research, who may afect the focus and direction of FMT research. He mainly focused on MS [14], such as insulin sensitivity, and obesity. Allegretti, Jessica R., and Kassam Zain from the US mainly focused on FMT for UC [63], IBS, and CDI. Cammarota Giovanni, Ianiro Gianluca, and Gasbarrini Antonio from Italy focused on FMT in CDI, psychiatric disorders [64], and cancer treatment [65]. Khanna Sahil from Mayo Clinic, Khoruts Alexander from University of Minnesota, and Kelly Colleen R. from Brown University in the USA mainly focused on FMT in rCDI [66,67]. Zhang Faming from Nanjing Medical University in China mainly focused on FMT in CD and UC, and some questionnaires and ethical issues on the perception of FMT among physicians and patient groups [68], and put forward the concept of washed microbiota transplantation (WMT) [69]. Notably, most of the top 10 authors participated in the formation of the FMT-related consensus [41,70]. In order to know the latest research progress in FMT research, we should focus on their work and give their research a relative priority.

Current Frontiers and Trends in FMT.
Common keywords are utilized to identify the hotspots, while the cluster analysis can locate the primary study materials under the hot topics. Common keywords and cluster analysis showed the primary status and hotspots in FMT, which mainly concentrated on the mechanism and treatment of FMT.
Currently, many studies have explored the clinical application of FMT, including the following aspects: (1) rCDI: Te most efcient and well-researched indication for FMT to date is rCDI. Numerous studies had shown that FMT was established as a highly restorative treatment for rCDI [71]. Several meta-analyses had shown considerable promise for FMT in rCDI [29,40,67,[72][73][74]. Te routes, infusions times, and fecal dose may afect the efcacy of FMT for rCDI [73]. Moreover, colonoscopy and the oral route were superior to stool enemas; FMT in relapsed CDI also was more efective than refractory CDI [67]. (2) IBD: IBD, especially UC, is another current hotspot in FMT. Two meta-analyses [75,76] showed that FMT may be safe and efcient for IBD treatment. FMT was an efcient way for the treatment of CDI in IBD patients [77], FMT may be a novel therapeutic option for IBD. Some systematic reviews and meta-analyses suggested that FMT is a safe, welltolerated, and efective treatment for certain diseases other than rCDI, with the most compelling evidence for active UC [78][79][80]. (3) IBS: Some studies have shown that FMT can help restore the GM and its function in IBS patients, and the richness and diversity of GM increased in IBS patients after FMT [8,81]. Two meta-analyses showed that delivery of fresh or frozen donor feces may be benefcial for IBS [82,83]. However, some studies also showed no disparity between FMT and control groups in RCTs in improvement or changes of the IBS symptoms and the living quality of patients, and FMT is considered inefective for IBS [78,83]. (4) MS: MS is a group of clinical syndromes characterized by central obesity, hyperglycemia, dyslipidemia, and hypertension, and insulin resistance serves as the common pathophysiological basis. Several studies had shown that FMT had advantages for MS, possibly improving insulin sensitivity by modifying the GM [13,27,84]. FMT may play a role in treating MS, but there is currently insufcient evidence to support its clinical practice [84]. (5) MD: Some papers showed that the pathogenesis of depression and anxiety disorders is closely linked to the changes of GM [15,48,49]. FMT may cure psychiatric disorders by adjusting the brain-gutbacteria axis, providing new ideas for depression and anxiety disorders. FMT can efectively enhance psychiatric disorders in recipient animals. Preclinical and clinical studies suggested that reversing or alleviating dysbiosis appears to be a promising strategy for restoring behavioral disorders or achieving remission of psychiatric symptoms [64].
At present, the evidence-based medical research of FMT mainly focuses on CDI, IBD, and IBS (Table 8). Notably, FMT may play a role in IBS treatment, but there is currently insufcient witness to support its clinical application. For example, a 2020 meta-analysis showed that FMT markedly enhanced clinical remission rates in active UC, but there was no apparent change in IBS symptoms after FMT [78]. In addition, although this bibliometric study and some clinical trials had shown the potential therapeutic efect of FMT in some diseases such as MD and MS, there is still a lack of evidence-based medical studies to further verify its clinical efcacy and safety. With the expansion of FMT application, more randomized controlled clinical studies will be available for evidence-based medical analysis.
Many studies explored the therapeutic mechanism of FMT, which may achieve therapeutic purposes by realizing new GM-host interactions, but the concrete origin of interactions remains unclear. Specifcally, the therapeutic effect of FMT is mainly mediated by the GM. Many studies show that there is a crosstalk among GM, metabolism, and immunity. GM dysbiosis can stimulate persistent infammation, and afect the host immune system and metabolism. GM and its metabolites are critical for the development of host immunity, and in turn, host immunity also afects the GM [85]. Te interaction of the GMmetabolome-immune network can be revealed through multiomics analysis, which is the current research focus [86]. Te normal GM maintains the balance of local immune responses and barrier integrity in the gut by exposing LPS and metabolites such as short-chain fatty acids [87]. Reactive oxygen species also have a key role in inducing programmed cell death and many diseases, and oxidative stress can be better known and controlled by tracking oxidative stress levels in feces to fnd proinfammatory components [88].
Tere are also some yellow nodes in other clusters, but they are scattered. Among them, neurological diseases (ND) and antitumor chemotherapy and immunotherapy research have received more attention in recent years, which may suggest future research directions. Te main keywords include AD, PD, chemotherapy, immunotherapy, and Clostridium difcile infection, showing that FMT in neurological diseases and antitumor drug treatment are the focus in the future. (1) Neurological diseases: GM plays a crucial role in the interplay between the gut and the brain, which could shape neurodevelopment, modulate neurotransmission, and infuence behavior, thereby afecting ND [16]. FMT may be a promising therapeutic option for several ND. Recent publications have highlighted GM imbalances in the development and progression of ND, and GM-related interventions may be used to treat neurological disorders [16]. FMT derived from AD mouse can impair memory function and neurogenesis in mice [89]. FMT can protect rotenoneinduced PD by inhibiting LPS-TLR4 signaling-mediated infammation via the microbe-gut-brain axis [90]. But the current research is still mainly focused on basic research. (2) Cancer treatment: Te GM may afect the efcacy and adverse efects of antitumor chemotherapeutics and immunotherapy. FMT is increasingly being studied to overcome cancer treatment resistance and side efects [91,92]. An animal study showed FMT can prevent chemotherapyinduced intestinal mucositis in colorectal cancer [93]. Specifc GM may contribute to chemotherapy-related side efects, and FMT can reverse chemotherapy-induced GM dysbiosis and side efects [94,95]. For immunotherapy, in 2015, two papers in Science pointed out that the efect of CTLA-4 inhibitor depends on GM, and FMT can improve antitumor immune response and facilitate anti-PD-L1 effcacy [52,53]. In 2018, two papers in Science found that the GM modulate antitumor response of the checkpoint blockade immunotherapy, and FMT can improve the efect of PD-1 inhibitors, which has important implications for research on the antitumor immunotherapy [50,51]. In 2021, two trials published in Science showed that FMT from ICI responders can overcome the resistance to immunotherapy [11,96]. Future eforts should focus on developing therapeutics targeting the GM. (3) Consensus and guidelines: Guidelines and consensus statements for FMT clinical practice can efectively standardize the diagnosis and treatment behavior of medical staf, improve the quality of medical services, and reduce medical costs. Several guidelines and consensus had been published regarding clinical FMT [41,70,97]. Fecal banks can give patients with consistent, timely, and equitable access to FMT, as well as traceable workfows to assure process safety and quality. An international consensus in 2019 provided detailed advice for FMT in clinical practice [70]. In addition, animal FMT has important implications for basic research, and the causal relationship between GM and disease models can be determined by performing FMT on animals such as mice [98]. A guideline reporting on animal FMT made detailed recommendations for FMT protocols from mice [99].

Limitations of the Study.
Te study also has several limitations. First, while the included papers adequately refect the current state, we retrieved data only from the SCI-Expanded of WoSCC database. Second, bibliometric surveys of newly published high-quality articles will be ignored. Inherent biases such as bibliometrics against recently published papers may cause some signifcant papers to not be included in these analyses because it takes time to accumulate citations. Tird, the impact of an article and the progress in a feld cannot be known by the citations alone, nor should a low publication rate in a country imply a lower quality of scientifc research. Terefore, there may be discrepancies between bibliometric analysis and real studies.

Conclusions
One of the study's main strengths is that by including all journals generated within the FMT study area, we generated a diverse top-cited composition of corresponding authors, journals, articles, countries, and institutions. Furthermore, research hotspots and trends connected to FMT are studied and projected using keyword analysis, providing study suggestions for future research. Further optimization of FMT methods, such as capsule preparations and frozen fecal bacteria, can reduce costs by reducing the number and frequency of donor screening, relieve patient discomfort during operation, and increase the acceptance of patients and medical staf, which has a good application prospect. Well-designed randomized controlled clinical studies and high-qualityevidence-based medical studies are needed to identify the best indications, maintenance methods, and transplantation pathways for FMT. Te safety assessment of FMT is still in its infancy, and the consensus has not yet been formed, and more in-depth research is still needed. With the extensive attention of researchers and the advancement of technology, future research on FMT is likely to get rapid growth and previously unexpected applications, fecal therapy will continue to improve beyond "whole fecal" transplants. Tis study displayed the global research state and trends of FMT using bibliometrics and graphical analysis. It helps scholars in allied domains with a better grasp of the development and evolution process of FMT and provides a reference for the use of FMT in new disciplines by summarizing existing research hotspots and projecting future development trajectories.

Data Availability
Te Web of Science database contains the original data that were used in the study. Te associated authors can be contacted for more information. Te search link was as follows: https:// www.webofscience.com/wos/woscc/summary/5c068744-8c95-48a4-858f-14d0d436fe16-483dcde5/times-cited-descending/1.

Ethical Approval
Since the bibliometric study's data were taken directly from the database with no further human involvement, ethical approval was not required.

Conflicts of Interest
Te authors declare that they have no conficts of interest.

Authors' Contributions
SH wrote and proofread the manuscript, investigated the study, designed the fgures, and responsible for production. SY wrote the manuscript, investigated the study, prepared the tables, and was responsible for production. NZ gathered data and edited the manuscript. HC inquired, approached, and supervised the work. Tis article was written by all authors, who also gave their approval to the fnal product. Shaodong Hao and Shanshan Yang made an equal contribution to this work.