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Safety comparison of single-donor and pooled fecal microbiota transfer product preparation in ulcerative colitis: systematic review and meta-analysis

BMC Gastroenterology volume 24, Article number: 402 (2024) Cite this article

Abstract

Background

Multiple studies have evaluated fecal microbiota transfer (FMT) in patients with ulcerative colitis (UC) using single-donor (SDN) and multidonor (MDN) products. Systematic review and meta-analysis were performed to compare the safety of SDN and MDN products.

Methods

Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence to identify studies that compared FMT products manufactured using SDN or MDN strategies against control treatment in patients with UC. Fifteen controlled studies were selected for meta-analysis (11 randomized controlled trials and 4 controlled cohort trials). Safety of each treatment type was assessed using the counts of adverse events and serious adverse events using fixed- and random-effects models. Significance of the indirect difference between FMT preparations was assessed using a network approach. Benefit-risk ratios were calculated by multiplicative utility model, incorporating geometric mean of risk ratios (RRs) of efficacy and safety.

Results

Safety data was collected for a total of 587 patients (193 exposed to SDN products, 114 exposed to MDN products and 280 exposed to control treatment). The 12 studies showed similar overall safety event counts for MDN and SDN versus placebo (RRs: 0.90 and 1.09, respectively [P = 0.206 and P = 0.420, respectively]). Results indicated similar risk of safety events for MDN compared to SDN (RR: 0.83, P = 0.159). Positive benefit-risk ratios were demonstrated for MDN and SDN versus placebo (RRs: 1.70 and 1.16, respectively [P = 0.003 and P = 0.173, respectively]). MDN had a greater benefit-risk ratio compared to SDN (RR: 1.46, P = 0.072).

Conclusion

Similar safety profiles were observed for MDN and SDN strategies. Alongside previously described superior efficacy, treatment with MDN has greater benefit-risk ratio than SDN in patients with UC. Further development of MDN FMT treatment for UC should be considered.

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Background

Ulcerative colitis (UC) is a chronic, inflammatory bowel disease causing inflammation of the mucosal lining of the colon and rectum. While the exact cause remains unknown, research suggests that UC could be sustained by microbial antigens released by over-abundant proinflammatory bacteria triggering aberrant immune activation and chronic inflammation [1]. Randomized controlled trials (RCTs) evaluating the potential of fecal microbiota transfer (FMT) to restore microbial diversity [2] and gut homeostasis have shown promising results in UC. In line with this, previous meta-analyses support the use of FMT as an effective treatment to induce remission in UC patients [3, 4]. However, the difficulty in defining a “good” donor as well as the intrinsic variability of donor-derived products’ taxonomic composition limits the translatability and reproducibility of these studies. Thus, the pooling of donors’ feces has been proposed to homogenize product composition and achieve higher taxonomic richness and diversity. The superior efficacy of multidonor (MDN) compared to single-donor (SDN) products to treat UC patients has been demonstrated in several clinical studies [5]. Nevertheless, due to the multiplicity of source materials used, new safety concerns may be associated with MDN FMT, such as an increased risk of AEs or SAEs, especially infection by undetected pathogens.

The present systematic review with meta-analysis of RCTs builds on Levast 2023 to compare safety of MDN and SDN microbiotherapy products in UC patients and perform a benefit-risk assessment incorporating efficacy and safety data. The same literature search was performed, with the difference of collecting data up to a later cut-off date of 12 September 2022. In this study, the intervention was FMT, MDN product preparation strategy was defined as FMT product made from at least 2 different donors and SDN product preparation was defined as FMT product made from 1 donor.

Methods

The systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method [6]. The protocol was registered with the Internation Prospective Register for Systematic Reviews (PROSPERO, registration number: CRD42020210649). The statistical analysis plan was locked before statistical analysis.

Search strategy and selection criteria

Two investigators (B.Le. and M.F.) independently performed a comprehensive literature research for articles, books, and abstracts related to the safety and efficacy of fecal microbiotherapies in inflammatory bowel disease, irrespective of language. The investigators searched for scientific articles containing clinical data on Scopus, PubMed, Web of Science, as well as Registers, and patents on Orbit Intelligence. They also identified records of interest by searching websites of organizations as well as through citation searching (see Supplemental Digital Content 1). Selected references were checked manually. The last search was performed on 12 September 2022.

B.Le. and M.F. independently assessed the abstracts of all selected articles for eligibility. Any disagreement was resolved by a third investigator (P.L.). Studies evaluating the safety and efficacy of fecal microbiotherapies in UC patients were selected. If several articles reported results associated with the same clinical trial, the article reporting the most extensive information was selected. Predesigned forms were used to independently assess eligibility of potentially relevant articles, according to predefined criteria. Studies were excluded after endpoint evaluation and because included patients did not meet the eligibility criteria for this analysis. Selected records were retrieved and further assessed for eligibility. A PRISMA flow diagram summarizing the selection process is presented in Fig. 1 [6].

Fig. 1
figure 1

PRISMA flow diagram showing the study selection process. n, number of records; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses. From Page et al. [6]

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All studies testing at least one efficacy endpoint and conformed to the following eligibility criteria were selected (Table 1):

  1. 1.

    All patients diagnosed with UC were selected. All variables such as follow-up duration, concomitant medication, sex, age or language were recorded and used as meta-regressive moderators;

  2. 2.

    Selected microbiotherapy interventions were FMTs administered at any individual treatment timepoint. FMT products were manufactured either with SDN or MDN strategies;

  3. 3.

    The following controls were considered as comparators in the study:Autologous FMT, defined as the patient’s own stool collected and stored at study inclusion, reconstituted and administered to the patient at the treatment timepoint. This allows to perfectly control the stool process and the potential benefit of the administration of exogenous microbiota. Potential changes in patient’s gut microbial composition between stool donation and autologous FMT treatment could introduce bias. In such case, the autologous FMT treatment could have a positive, negative, or neutral therapeutic effect on the patient;

    1. i.

      Autologous FMT, defined as the patient’s own stool collected and stored at study inclusion, reconstituted and administered to the patient at the treatment timepoint. This allows to perfectly control the stool process and the potential benefit of the administration of exogenous microbiota. Potential changes in patient’s gut microbial composition between stool donation and autologous FMT treatment could introduce bias. In such case, the autologous FMT treatment could have a positive, negative, or neutral therapeutic effect on the patient;

    2. ii.

      Saline buffer, administered into the patient’s gut, is the best inert control compared to FMT administration. While the quality of the blinding process is not as good for saline buffer as it is for autologous FMT, no activity bias is expected;

    3. iii.

      Standard medical therapies (e.g., 5 aminosalicylic acid, topical steroids) or specific diet interventions (e.g., anti inflammatory or UC exclusion diets) used to treat UC are expected to have therapeutic effects and are important to consider in the benefit-risk assessment of microbiotherapy products.

Table 1 Characteristics of eligible studies
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Study selection and data collection are described in Supplementary Materials.

Outcome assessments

To assess the safety of FMT treatments against controls, the main safety endpoint was the count of adverse events (AEs) and serious adverse event (SAEs) occurring during the follow-up. The safety analysis was based on all selected studies which had AE or SAE comparison available. Separate analyses were conducted considering the count of:

  1. 1.

    AEs only;

  2. 2.

    SAEs only;

  3. 3.

    AEs and SAEs.

The benefit/risk ratio (BRR) compared the overall efficacy and safety of SDN and MDN versus controls and was analyzed using all selected studies. BRR is the unweighted ratio of the risk ratios (RR) of efficacy (Binary therapeutic response) on safety (occurrence of AE and SAE) compared with control and log-transformed to preserve normality properties [7, 8].

Data availability

All data generated and analyzed during this study are included in this published article and its supplementary information.

Meta‑analysis

All studies were analyzed for certainty of evidence based on the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach [9]. The Cochrane Collaboration’s risk-of-bias tool [10] was used to evaluate bias and filled in by 3 reviewers on the 15 controlled studies, among which 12 had available safety comparison data and were included in the safety analyses (Table 2). Each study was separately analyzed for risk of bias or indirectness. Heterogeneity (using a random model), imprecision, and publication bias (using funnel plots) were evaluated at the meta‑analysis level. Meta-regression was performed using evidence level as moderator. The significance of the indirect estimate of the difference between MDN and SDN treatments was sought through a frequentist network approach [11]. The risk ratio (RR) was calculated as the main calculation of effect size. A random-effects model was assumed to be most likely where difference may be expected among studies, and the fixed model was performed for sensitivity purposes. All results were compared with an alternative fixed statistical model, and heterogeneity tests were used. Correlated pairwise comparisons in multiarm studies were corrected by the weight reduction approach [12]. Model fit was assessed by generalized Cochrane Qt [13, 14]. Treatment ranking by P-scores measured the extent of certainty that any one treatment was better than another, averaged over all competing treatments [15]. Statistical analyses were performed using R statistical packages (version 3.2.4) and the meta-library Netmeta [16].

Table 2 Selected studies
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Data values provided as standard error of the mean (SEM) were converted into SDs as per the formula SD = SEM*sqrt(n). For endpoint calculation and effect size, given the heterogeneity of the studies in their clinical definition, the following transformations were also needed for direction and measurement.

  1. 1.

    Severity scores (higher values meaning higher severity) were converted into improvement scores;

  2. 2.

    Two alternative methods were used to aggregate scales based on quantitative values or proportions:

    1. i.

      Converting the proportions x/n into quantitative values in assimilating this value to a normal approximation of mean (P = x/n and SD = √(P(1-P))/n);

    2. ii.

      Conversion of quantitative difference distributed according to a normal distribution N(m,σ), assuming a success proportion of 0.5 for the tested drug.

The difference between SDN and MDN strategies was analyzed comparing all selected studies, and sensitivity analyses were performed by excluding studies with Moderate Certainty of Evidence (MCE) for each studied arm and for both arms as follows:

  1. 1.

    Analysis of studies with High Certainty of Evidence (HCE) for MDN and all studies of SDN;

  2. 2.

    Analysis of studies with HCE for SDN and all studies of MDN;

  3. 3.

    Analysis restricted to studies with HCE for both MDN and SDN.

The efficacy of MDN and SDN was also assessed separately vs placebo in discussing the heterogeneity and directness of the studies. Finally, meta-regressions were conducted by using the available baseline variables as potential moderators with the double purpose of assessing the confounding effect of publication date and type of study (RCT vs non-RCTs). For each covariate, a factorial model was used in testing the treatment effect, the covariate effect, and its possible interaction with the treatment. Given the low expected power of the interaction, a maximum P value of P = 0.2 was considered as significant.

Risk of bias and certainty of evidence

Risk of bias and certainty of evidence are tools that were used to measure the quality of selected studies and resulting meta-analytical results. They are detailed in [17,18,19,20]. We summarize them in adding quantification of some conditions (Supplementary Material).

Results

The search identified 1846 records in medical databases (376 records after deduplication) and 285 records from other sources (Fig. 1). After exclusion of 332 studies, 44 records were retrieved and assessed for eligibility. The main criteria for further excluding studies were nonpredominance of patients with UC over those with Crohn’s disease or pouchitis and case reports with fewer than 4 patients. Four pediatric studies were included (n = 48 exposed to FMT). Only 1 report identified by the patient search tool could be retrieved and assessed for eligibility [21]; this was also identified in medical database search.

From the 44 studies identified (29 noncontrolled studies, 11 RCTs, and 4 controlled cohort [CC] studies), 15 studies with a control arm were selected as eligible [22]; 29 studies were non-controlled and were therefore excluded from the analyses. Of the 15 eligible studies, only 12 had safety comparison data available and were included in the safety analyses. Most patients in the selected studies were adults with UC; there were a few patients with Crohn’s disease who were not considered in the calculation. Overall, 567 patients with UC were considered, with 173 exposed to SDN products, 114 exposed to MDN products and 280 exposed to controls. Disease history, grading, and follow-up were heterogenous between studies but documented in this work.

Main findings from individual studies

The variables were the number of AEs and SAEs reported in each study. There were 44 identified studies, 29 of them excluded and 15 deemed eligible. Characteristics of the 44 eligible studies are provided in Table 1 by study design, studied treatment group, sample size, number of AEs and treatment type (SDN or MDN) and for the 15 selected studies in Table 2. In the 15 selected studies, safety data considering between 1–84 FMT administrations over 2–48 weeks across countries in North America, Europe and Asia were evaluated. Most studies used the lower route of FMT administration, however the upper route and capsules were represented in 1 [23] and 2 [24, 25] studies, respectively. The MDN strategy was compared with controls in 3 RCTs [2, 22, 26], which reported 32 AEs and 2 SAEs in 41 patients, 3 SAEs in 38 patients and 26 AEs in 35 patients with FMT treatment and 33 AEs and 1 SAEs in 40 patients, 2 SAEs in 35 patients and 27 AEs in 31 patients with control treatments, respectively. The SDN strategy was compared with control treatments in 8 RCTs [23,24,25, 27,28,29,30,31] and 1 CC study [32].

Risk of bias and indirectness within studies

An acceptable risk of bias was determined for all controlled studies and is presented in Table 3. However, as a CC study was included in the meta-analysis, sensitivity analyses were needed to compare results. The selected studies were similar to routine medical practice in terms of patient population, interventions, comparators, and outcomes, confirming that there was no indirectness within this study. External validity is synonymous with indirectness when assessing whether the data include the population, intervention, comparator, and outcome in routine medical use.

Table 3 Summary of certainty of evidence, including risk of bias and directness for controlled studies
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Based on risk of bias and directness, 5 studies were considered as HCE (Rossen, Moyaedi, Paramsothy, Costello and Haifer), the 10 others associated as MCE (Table 3).

Synthesis of results: safety assessment

The sample size and number of AEs and SAEs for each treatment group in each selected studies are summarized in Table 1.

The 12 selected studies had HCE/MCE and compared MDN or SDN with control treatment. No substantial differences between fixed- and random-effects models were observed in all safety analyses, henceforth, results of the random-model are presented. Risk of AE/SAE occurrence tended to be reduced with FMT treatment, as indicated by risk ratios (RRs; 95% confidence intervals [CIs]) for comparisons of MDN and SDN versus control, 0.90 ([0.77; 1.06], P = 0.206) and 1.09 ([0.88; 1.34], P = 0.421), respectively (Fig. 2). Furthermore, a tendency towards lower risk of AE and SAE occurrence was observed in MDN versus SDN (RR [95% CI]): 0.83 ([0.64; 1.08], P = 0.159), with considerable homogeneity shown across all studies (generalized Cochran for homogeneity, P = 0.480, I2 = 0%). P-scores associated with control, SDN and MDN were 0.446, 0.145 and 0.909, respectively for both the fixed- and random-effects models.

Fig. 2
figure 2

Forest plot of safety analysis for all safety events. CI, confidence interval; MDN, multidonor; RR, risk ratio; SDN, single donor. Comparison of SDN and MDN was performed by using placebo as the null reference. RR SDN/placebo and MDN/placebo

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For sensitivity purposes the analysis was performed individually for AEs and SAEs, on studies with available comparison with control treatment. Considering the 7 studies with available AE comparison, similar results were estimated for comparative risk (RRs [95% CIs]) of AEs occurring with MDN and SDN versus control, 0.90 ([0.72; 1.12], P = 0.333) and 1.05 ([0.83; 1.35], P = 0.655), respectively. MDN tended to have a reduced risk of AE occurrence versus SDN (RR [95% CI]): 0.85 ([0.65; 1.12], P = 0.244). Regarding the 8 studies with available SAE comparison, results indicate a similar risk (RRs [95% CIs]) of SAE occurrence with both MDN and SDN versus control, 1.56 ([0.39; 6.25], P = 0.533) and 1.77 ([0.90; 3.49], P = 0.100), respectively. The risk of SAE occurrence in MDN and SDN was similar (RR [95% CI]): 0.88 ([0.19; 4.14], P = 0.871).

Benefit-risk evaluation

Benefit-risk ratios were calculated by multiplicative utility model, incorporating geometric mean of RRs of efficacy (binary therapeutic response, Levast 2023) [5] and safety (occurrence of AEs/SAEs). Tests of heterogeneity within designs and inconsistency between designs were performed and demonstrate a non-significant study effect (P = 0.18). Positive benefit-risk ratios [95% CI] calculated for both MDN and SDN versus control were 2.61 ([1.26; 3.95], P ≤ 0.001) and 1.43 ([0.67; 2.18], P ≤ 0.001), respectively (Fig. 3). MDN had a higher benefit-risk ratio compared to SDN [95% CI]: 1.18 ([-0.36; 2.72], P = 0.133).

Fig. 3
figure 3

Forest plot of benefit-risk analysis. CI, confidence interval; MDN, multidonor; RR, risk ratio; SDN, single donor. Comparison of SDN and MDN was performed by using placebo as the null reference. RR SDN/placebo and MDN/placebo

Full size image

Discussion

Through systematic review and meta-analysis, this study has collected data from studies of FMT treatments to compare the safety of FMT products prepared by single and multi-donor strategies in patients.

With the implementation of FMT as a well-recognized, approved, and life-saving therapy for the management of recurrent Clostridioides difficile infection, the short-term outcome and safety of FMT has been well documented [33]. When guidelines for the screening of donors and fecal material are followed, FMT treatment appears to be highly safe [34], with only transient, mainly gastrointestinal side effects and risks attributable to the method of administration (endoscopic procedures) rather than FMT itself [35, 36]. In the 15 studies selected for this analysis, most commonly reported AEs following FMT were mild and transient, consisting of abdominal discomfort, bloating, flatulence, diarrhea, nausea and low-grade fever. Most studies report that FMT-related AEs happened within hours following FMTs and were usually resolved under 48 h, in line with literature reports [37]. The study by Sood and colleagues [25] is the only study where the occurrence of AEs was followed through time, after each FMT administration. In this study, no significant difference in the number of AEs was observed between the placebo and FMT groups over time. In all other studies, AEs numbers were reported as the total of AEs that occurred during the follow-up period ranging from 2 to 48 weeks (Table 1), regardless of the number of FMT administrations. Only few or no SAE were documented in these studies, mostly consisting in colitis, worsening of UC disease activity or appearance of new conditions that were deemed unrelated to treatments. In particular, similar AEs and SAEs were reported in studies using either SDN or MDN products. These results are in line with the most common AEs described in the literature in response to FMT procedure, occurring in roughly 29% of patients and usually resolved under 48 h [37].

This analysis demonstrates similar safety profiles of SDN and MDN strategies with regards to AE/SAE counts. Weighing greater efficacy and comparable safety, an appreciable benefit-risk ratio of MDN FMT preparation over SDN was observed. In the context of an unmet medical need for relapsing UC and the relatively recent knowledge about fecal microbiota, this study provides a good overview of what a pooling strategy can bring to healthcare providers both in term of safety profile and treatment efficacy.

Despite promising results, the translatability and reproducibility of FMT treatment in UC patients remains limited due to the intrinsic variability of taxonomic composition of donor-derived products [38]. Because the objective of FMT is to restore a healthy microbial ecosystem in patients, the richness and diversity of FMT products is critical. Indeed, differences in donor stool composition translate into major changes in engraftment dynamics, directly affecting treatment efficacy. Moreover, microbial diversity was identified as a reliable predictor of FMT success [39,40,41]. In this respect, MDN microbiotherapies were designed to homogenize product composition, achieve higher taxonomic richness, and enrich specific bacterial genera with health benefits such as butyrate-producing bacteria to improve patient care [42]. In line, preclinical research has demonstrated the superiority of MDN microbiotherapies compared to corresponding SDN products to protect against infectious diseases in mice [43]. Similarly, prior research shows significant clinical benefit for UC patients treated with MDN and published meta-analysis indicates increased efficacy over SDN [5]. Enhanced efficacy may depend on donors possessing microbial taxa complementary to those lacking in receiver patients, conceivably easier to achieve with pooled FMT from multiple donors [40, 41]. Standardization of FMT preparation permits consistency between FMT treatments of a batch and can be used to generate product with greater certainty of safety and efficacy [44].

Alongside the advantage of using multiple donors to maximize microbial diversity of the prepared FMT product, importance must be placed upon the effect the recipient has on the outcome of FMT treatment. The interaction between the recipient’s uniquely composed endogenous microbiota and the bacteria introduced by FMT will influence both efficacy and safety of the treatment [45, 46], thus a personalized treatment would be ideal to maximize clinical benefit.

Although this study shows comparable safety of MDN and SDN strategies, pooled treatments have some hypothetical limitations. A greater number of donors contributing to a FMT preparation increases the chance of altering the recipient’s gut microbiome to the extent that they become prone to developing chronic conditions (e.g., autoimmune disorders) [47]. Additionally, an AE resulting from a donor’s sample would be challenging to determine the source donor and to correct the FMT product [42]. These potential issues emphasize the importance of donor selection and the processing and screening of samples in the manufacture of FMT product.

Efforts have been made to improve the preparation of FMT; washed microbiota transplantation, involving optimized automatic purification and centrifugation of microbiota has been shown to significantly reduce the rate of related AEs versus manual methods of FMT preparation [48, 49]. The washing method reliably reduced incidence of FMT-related AEs due to the improved intestinal mucosal permeability and decreased levels of proinflammatory metabolites of the washed preparation. Further refinement of standardized FMT processing may improve patient safety.

This study has limitations, and the meta-analysis should be verified by large-scale dedicated RCT. Because of the lack of standard protocol or regulatory framework to standardize FMT administration procedures, the studies described here are representative of the high heterogeneity of FMT-related clinical trials found in the literature. Differences in the dose or number of FMTs could affect the outcomes of the studies, as repeated administrations have been linked with higher response rates in patients with irritable bowel syndrome [50]. Of note, other factors can also influence the study results, such as the mode of delivery or the administration of concomitant treatments (Table 1). As such, the MDN FMT strategy is one of many ways to improve FMT procedures through standardization of microbial taxonomic composition and richness. A variety of control types were observed across the selected studies: autologous FMT, placebo (saline buffer) and standard medical therapy. All control types may each generate a different patient response to treatment, thereby affecting comparability and introducing a potential risk of bias to the meta-analysis. Meta-regressions on predictors at baseline, considering the therapeutic response were presented in Levast 2023 and indicated strong clinical benefit of the capsule formulation of FMT and antibiotic gut preparation before FMT treatment. These meta-regressions could be calculated using safety outcome data to estimate if the same predictors have a similar positive impact on the number of AEs and SAEs experienced by patients treated with FMT. Capsules have also been identified as a route of FMT treatment worthy of pursuit in recently published review [3] and a study for the indication of C. difficile infection found FMT capsules to have fewer AEs compared to lower route of administration [51]. The meta-analysis considered the count of AEs and SAEs; a detailed analysis of the nature of individual events could further inform the benefit-risk assessment of FMT treatments.

The variability of how AEs and SAEs are defined in each included study is also a concern that is inherent to meta-analysis. For example, a higher proportion of SAEs in patients receiving active FMT treatment was reported in [29] compared to other trials, probably due to a less stringent definition of SAEs [29]. Indeed, patient hospitalization was always classified as a SAE, even if this was necessary solely to initiate intravenous steroid treatments for active colitis. Development of C. difficile infection was also classified as a SAE, despite being unable to differentiate a recurrent infectious episode from an inflammatory UC flare. Most but not all selected studies had a description of AEs and SAEs, and the exact proportion of the symptoms contributing to the total reported AEs was also not provided in all studies. Thus, it was not possible to define and use our own criteria to stratify AEs and SAEs more accurately. Nevertheless, an analysis accounting for Common Terminology Criteria for Adverse Events (CTCAE) grading, relatedness to treatment, and system organ class analysis would provide this additional insight.

Conclusions

In conclusion, this systematic review and meta-analysis reveals similar safety profiles of MDN and SDN strategies in UC patients. Combined with favorable efficacy, MDN has a slightly higher benefit-risk ratio compared to SDN. Although these results support further development of pooled microbiotherapies in UC patients, they must be interpreted with caution due to the aforementioned limitations, and should be tested in RCT studies including a higher number of patients. Alternatively, a study comparing SDN and MDN treatments could be of great interest to resolve this question and improve UC patients care.

Data availability

All data generated and analyzed during this study are included in this published article and its supplementary information.

Abbreviations

AE:

Adverse event

CC:

Controlled cohort

CI:

Confidence interval

FMT:

Fecal microbiota transfer

GRADE:

Grading of Recommendations, Assessment, Developments, and Evaluations

HCE:

High certainty of evidence

MCE:

Medium certainty of evidence

MDN:

Multidonor

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO:

International Prospective Register of Systematic Reviews

RCT:

Randomized controlled trial

RR:

Risk ratio

SAE:

Serious adverse event

SD:

Standard deviation

SDN:

Single donor

SEM:

Standard error of the mean

UC:

Ulcerative colitis

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Acknowledgements

Medical writing support by Veristat is acknowledged together with any financial support for the study.

Funding

The study was funded by MaaT Pharma, France; http://www.maatpharma.com. An unconditional grant was provided to the authors, and MaaT Pharma was not involved in writing the protocol, statistical plan, or discussion of results.

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Authors and Affiliations

  1. MaaT Pharma, Lyon, France

    Bastien Laperrousaz, Benoît Levast & Mathieu Fontaine

  2. Department of Gastroenterology, Lyon-Sud Hospital, CHU de Lyon, University Claude Bernard Lyon 1 and CIRI-INSERM U1111, Lyon, France

    Stéphane Nancey

  3. CHU Rouen, Rouen Normandie University, INSERM 1073, Rouen, France

    Pierre Dechelotte

  4. Université Paris-Saclay, INRAE, MetaGenoPolis, AgroParis Tech, MICALIS, Jouy-en-Josas, 78350, France

    Joël Doré

  5. Faculty of Management, UCL, Louvain, Belgium

    Philippe Lehert

  6. Faculty of Medicine, University of Melbourne, Melbourne, Australia

    Philippe Lehert

Authors
  1. Bastien Laperrousaz
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  2. Benoît Levast
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  3. Mathieu Fontaine
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  4. Stéphane Nancey
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Contributions

B.La., B.Le. and M.F. performed the literature review. P.L. designed the study, calculated the meta analysis, performed all statistical tasks, scored the GRADE and quality of studies and participated in the data monitoring committee. B.Le. scored the GRADE and quality of the studies. B.La. wrote the manuscript. S.N. and J.D. contributed to discussions and reviewed the manuscript. All authors contributed to discussions, reviewed the manuscript and approved the final version of the article. Editorial support was provided by Veristat.

Corresponding author

Correspondence to Bastien Laperrousaz.

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Competing interests

The study was funded by MaaT Pharma, France; http://www.maatpharma.com. An unconditional grant was provided to the authors, and MaaT Pharma was not involved in writing the protocol, statistical plan, or discussion of results.

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Laperrousaz, B., Levast, B., Fontaine, M. et al. Safety comparison of single-donor and pooled fecal microbiota transfer product preparation in ulcerative colitis: systematic review and meta-analysis. BMC Gastroenterol 24, 402 (2024). https://doi.org/10.1186/s12876-024-03487-2

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BMC Gastroenterology

ISSN: 1471-230X

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