Remission rates and safety of fecal microbiota transplantation in inflammatory bowel disease in adult patients: A systematic review

Abstract

Background:

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic gastrointestinal disorder that substantially impairs quality of life. Conventional therapies are often limited by suboptimal efficacy, adverse effects, and diminishing response over time. Fecal microbiota transplantation (FMT) has emerged as a therapeutic strategy aimed at restoring microbial balance, reducing inflammation, and improving outcomes.

Objectives:

To systematically evaluate clinical remission rates and safety profiles of FMT in IBD.

Design:

A systematic review of randomized controlled trials, controlled clinical trials, and observational studies, reported in accordance with the PRISMA-2020 guideline.

Data sources and methods:

Searches were conducted in Google Scholar (November 17, 2024) and Scopus (November 19, 2024). Eligible studies included randomized controlled trials, controlled clinical trials, and observational studies published after 2015 that reported remission and/or safety outcomes in adult IBD patients. Reviews, protocols, pediatric or animal studies, non-English publications, and non-peer-reviewed sources were excluded. Risk of bias was assessed using an adapted Cochrane approach, with common concerns relating to blinding and subjective outcome assessment.

Results:

From 309 records, 22 studies met inclusion criteria. Mean remission rates were 46.6% for FMT via colonoscopy (41.75% for CD and 47.17 for UC), and 58.13% for alternative routes (capsules, enemas, tubes), yielding an overall mean remission of 47.61%. Adverse events were generally mild gastrointestinal symptoms; serious events were rare, including infections and procedure-related complications.

Conclusion:

FMT, particularly via colonoscopy, appears effective and generally safe for IBD. However, heterogeneity in donor selection and protocols, limited long-term data, and English-language restriction constrain generalizability. Larger, standardized, and longer-term trials are needed to consolidate evidence.

Trial registration:

This study was registered post-study at INPLASY registration number: INPLASY202620020, and no formal protocol was prepared; conducted as a coursework project but adhered to prespecified criteria and PRISMA-2020 reporting. Consequently, no amendments were made to the information provided at registration or in the protocol.

Keywords

inflammatory bowel disease fecal microbiota transplantation systematic review clinical remission safety Crohn’s disease ulcerative colitis

Background

Inflammation of the gastrointestinal tract arises from various factors, including infections, toxins, autoimmune responses, or ischemic conditions. In the absence of definitive causes, chronic inflammatory bowel diseases (IBDs), notably ulcerative colitis (UC) and Crohn’s disease (CD), may develop.¹ UC is a chronic inflammatory disorder that predominantly affects the colon, typically in the rectal area. Common symptoms encompass bloody diarrhea, abdominal discomfort, and weight loss. The inflammation is generally superficial and categorized as proctitis, left-sided colitis, or pancolitis, with potential involvement of the terminal ileum as backwash ileitis.¹ In contrast, CD, recognized by Burrill Crohn, impacts any segment of the gastrointestinal tract, with a focus on the terminal ileum. Symptoms include abdominal pain, diarrhea, and weight loss.¹

Fecal microbiota transplantation (FMT) is an emerging therapeutic modality that involves the transfer of gut microbiota from a healthy donor to a recipient through the gastrointestinal tract, aiming to restore microbial diversity and ameliorating disease.² It is an established treatment for recurrent Clostridioides difficile infection (CDI) and has become increasingly accessible due to stool banks. Research suggests that gut microbiota dysbiosis is linked to various conditions. Randomized controlled trials have shown FMT to be moderately effective in treating UC, irritable bowel syndrome, and hepatic encephalopathy.³ Although FMT is established for treatment of recurrent CDI, its effectiveness and safety in IBD remain under investigation. Despite the increasing use of FMT in clinical practice, uncertainties persist regarding the magnitude of benefit, optimal delivery routes, donor selection, and long-term safety. Heterogeneity in FMT protocols and donor microbiota composition has limited cross-study compatibility and prevented standardized recommendations. These gaps highlight the need for a comprehensive synthesis of recent evidence.

Focusing on remission rates is essential to evaluate FMT’s efficacy, while understanding its safety ensures that risks are well documented. This dual focus is critical for informed clinical decision and patient care. Given the growing interest in FMT as treatment for UC and CD, a comprehensive review of its impact on remission rates and safety is necessary to evaluate its clinical viability for IBD patients.

This systematic review aims to evaluate the efficacy of FMT in inducing remission in patients with IBD, and to assess its safety, including potential adverse effects, to determine its feasibility as a treatment. This review seeks to address current gaps in the literature by focusing on studies published after 2015, when more standardized FMT methodologies emerged, and by applying PRISMA-2020⁴ reporting to enhance transparency and reproducibility. This provides a clearer understanding of FMT’s role in managing IBD and contributes to the ongoing discussion of alternative treatment options.

Methods

The reporting of this systematic review conforms to the PRISMA-2020⁴ statement.

Eligibility criteria

Studies were excluded if they involved pediatric populations, animal models, or non-peer-reviewed sources.

Inclusion criteria were as follows:

- Studies focusing on FMT in the management of IBD, including CD and UC.

- Clinical trials (randomized controlled trials, controlled clinical trials, and observational studies) published after 2015.

- Studies reporting outcomes on clinical remission rate, safety, adverse events, long-term symptom management, or mechanisms of FMT.

Exclusion criteria included:

- Review articles, protocols, commentaries, and case reports.

- Studies not published in English.

Studies published from January 2015 to November 2024 were considered and grouped for synthesis based on study design, disease type, and reported outcomes.

Information sources

The following sources were searched:

- Google scholar: Search conducted for studies using key terms related to FMT and IBD, including safety and efficacy.

- Scopus: Search conducted using TITLE-ABS-KEY criteria with specific terms for IBD, FMT, treatment, and safety. Filters excluded reviews and protocols and limited results to publications after 2015.

The last search was conducted on November 17, 2024 for Google Scholar and November 19, 2024 for Scopus.

Search strategy

Google scholar

Search terms: “fecal microbiota transplantation” AND “inflammatory bowel disease” AND (“safety” OR “adverse effects”) AND (“clinical trial” OR “observational study” OR “controlled clinical trial” OR “randomized controlled trial”) -review (last search: November 17, 2024). The search was entered exactly as shown, with quotation marks and Boolean operators to ensure reproducibility. Results: 190 studies identified; relevant papers based on the title were uploaded to Zotero.

Scopus

Search terms: TITLE-ABS-KEY (“inflammatory bowel disease” OR “IBD” OR “Crohn’s disease” OR “ulcerative colitis”) AND TITLE-ABS-KEY (“fecal microbiota transplantation” OR “FMT”) AND TITLE-ABS-KEY (“treatment” OR “therapy” OR “safety” OR “adverse effects” OR “efficacy”) AND TITLE-ABS-KEY (“clinical trial” OR “observational study” OR “controlled clinical trial” OR “randomized controlled trial”) AND PUBYEAR > 2015 AND NOT TITLE-ABS-KEY (“review” OR “protocol”) AND (LIMIT-TO (OA, “all”)) (Last search: November 19, 2024).

Results: 119 studies identified relevant papers based on the title were uploaded to Zotero.

Filters and limits: Articles published after 2015, excluding reviews, protocols, and non-English studies.

Selection process

The selection process involved 5 reviewers, who screened 212 papers. The process was divided into two stages:

- Title and abstract screening: Each reviewer independently screened the title and abstract of 40 studies based on the inclusion and exclusion criteria. Disagreements were resolved through discussion. Studies were excluded for the following reasons:

• Focus on biological therapies not FMT.

• Studies addressing CDI or unrelated diseases/interventions.

• Studies lacking information on clinical remission rates, safety, adverse events, long-term symptom management, or mechanisms of FMT.

This step narrowed the pool to 60 studies that matched the criteria. After removing duplicates, 55 studies moved to the next stage.

Full-text screening: Each reviewer evaluated 11 full-text articles. Studies that lacked information on remission rates or safety outcomes for FMT were excluded. By the end of this step, 24 papers were identified as eligible.

Final selection: After a collective review, two papers were excluded due to low patients’ number.

Data collection

Data collection was carried out by five independent reviewers, with each study’s data extracted in duplicate to ensure accuracy. Each reviewer extracted data from their assigned studies, and a second reviewer cross-verified the information. Disagreements were resolved by consensus or, by a third reviewer. The data extraction process involved filling out four separate tables for each study (Supplemental Tables 1–3).

Independence and data validation

Each reviewer worked independently to minimize bias. After extraction, the reviewers cross-checked their findings to ensure consistency. Discrepancies were resolved by discussion; if no consensus was reached, a third reviewer made the final decision. Data were managed and stored using Zotero and Microsoft Excel spreadsheets. No automation tools were used for extraction.

Data items and outcomes

The following prespecified outcome domains were targeted in the included studies, as defined in the eligibility criteria:

- Clinical remission rate:

Definition: The lessening of disease symptoms; the period during which this reduction takes place. (Medical dictionary)

• Results sought: Data on clinical remission rates were sought from studies that explicitly reported this outcome.

• Data collection approach: If a study reported clinical remission rates, the relevant data were collected. If not, this was marked as “Not specified.”

- Adverse events:

Definition: Negative side effects or complications related to FMT treatment, including gastrointestinal symptoms or more severe events.

• Results sought: Data on adverse events were sought from all studies that specifically reported any negative effects or complications experienced by participants.

• Data collection approach: If not provided, this was marked as “Not specified.”

- Long-term symptom management:

• Results sought: Data on long-term symptom management, such as the duration of remission and the time to sustained clinical response were recorded.

• Data collection approach: If not provided, studies were marked as “Not specified.”

- Safety:

Definition: The overall safety of FMT, considering short-term and long-term side effects or complications.

Results sought: Safety data were recorded, including any adverse events or complications.

Data collection approach: If not specified, the result was recorded as “Not specified.”

Methods used to decide which results to collect

No additional analysis or assumptions were made if a result was missing. This ensured transparency in data collection while maintaining consistency across studies. Studies that provided data on at least one of the primary outcomes, remission rate or safety, were included in the final synthesis and further analyzed in the “Results” and “Discussion” sections.

Risk of bias

The assessment of bias risk in the studies was conducted using criteria derived from the Cochrane Risk of Bias Tool (version 2.0).⁵ Each study was analyzed across three principal domains: two reviewers independently assessed risk of bias, and disagreements were resolved through discussion or consultation with a third reviewer.

Randomization—This domain evaluated whether suitable protocols were implemented for the allocation of participants.

Blinding—This aspect examined if participants, investigators, or outcome assessors were blinded to mitigate performance and detection bias.

Outcome assessment—This domain focused on clarity, objectivity, and consistency in the measurement and reporting of outcomes.

Each domain was classified as having a “Low,” “High,” or “Moderate” risk of bias, depending on the methodologies employed in the studies. Reviewers independently evaluated each study in duplicate, and any discrepancies were addressed through discussion. The bias assessment process did not utilize any automated tools.

Effect measures

For the synthesis and presentation of results, the following effect measures were employed:

Remission rates: Represented as proportions (percentages) of patients who achieved clinical remission, which was defined in each study through validated scoring systems such as the Harvey–Bradshaw Index (HBI) for CD, along with similar criteria for other conditions.

Safety outcomes: Reported qualitatively and classified into categories of mild (e.g., gastrointestinal symptoms), moderate, and severe adverse events (e.g., infections or procedure-related complications). Effect measures for categorical outcomes were synthesized using descriptive statistics, including means, ranges, and standard deviations. Raw numbers were converted to percentages for consistency. The use of proportions for remission and categorical classification for safety was chosen due to variability in study designs and outcome definitions, which precluded meta-analysis. We documented any differences in outcome definitions across studies and reported them narratively.

Synthesis methods

Studies were grouped according to intervention characteristics, patient populations, and study methodologies relative to the prespecified inclusion criteria: FMT via colonoscopy, alternative approaches (capsules, enemas, tubes), and comparative treatment. Data preparation involved extracting and standardizing remission rates, ranges, and standard deviations. Missing values were marked as “Not reported” and excluded from quantitative summaries but described narratively; ambiguous values were omitted to maintain integrity. Results were tabulated and described narratively, with descriptive statistics calculated using Python (Version 3.0, Pandas).^6,7 Descriptive analyses were necessary due to marked heterogeneity in study design, populations, intervention, and outcome definitions, precluding meta-analysis. A PRISMA flow diagram illustrates study selection.

Heterogeneity was explored qualitatively by comparing delivery methods, baseline patient characteristics, and donor microbiota composition. Subgroup analyses were not performed due to insufficient data. Sensitivity analyses were not conducted as no statistical pooling was undertaken, through future meta-analyses could incorporate such testing. Risk of bias from missing results was not formally assessed, as all studies reported relevant outcomes. Certainty of evidence was likewise not graded using tools such as GRADE because of the descriptive synthesis, and substantial heterogeneity that prevented meta-analysis.

Results

Study selection

In total, 309 records were identified from the databases. After screening the titles and abstracts, 60 studies were shortlisted. Duplicate records (n = 5) were removed, leaving 55 studies for full-text assessment. Thirty-six studies were excluded because they were qualitative and irrelevant to the focus of this review. Twenty-four studies initially met the inclusion criteria; however, 2 were excluded due to a low number of patients (n < 9), resulting in a total of 22 studies included in the analysis. These studies specifically examined the remission rates and safety of FMT in patients with IBD. The study selection process is illustrated in the PRISMA flow diagram, which details the number of records identified, screened, excluded, and included, along with reasons for exclusion at each stage (Figure 1).

Figure 1.

PRISMA 2020 flow diagram summarizing the identification, screening, eligibility, and inclusion of studies in the systematic review.

Characteristics of included studies

The 22 studies encompassed a mix of randomized controlled trials, controlled clinical trials, and observational designs, published between 2015 and 2024. Sample sizes ranged from 9 to 174 participants, with patient populations diagnosed with UC, CD, or indeterminate colitis. Interventions included FMT delivered via colonoscopy, capsules, enemas, and nasojejunal/nasoduodenal tubes. Control groups, when present, received placebo, autologous FMT, or standard care. Follow-up durations varied from 4 weeks to 12 months. Outcomes reported included clinical remission, adverse events, long-term symptom management, and safety profiles. Variability in donor selection, stool preparation, and pretreatment protocols was noted across studies (Table 1).

Table 1.

Individual study outcomes.

Study ID	Study design	IBD subtype	Sample size	Intervention type	Remission rate	AEs
Březina et al.⁸	Randomized controlled trial	UC	45	FMT enemas	57% in FMT group at week 12. Endoscopic remission 14% at week 6 and 14% et week 12	57% in FMT group, out of which 19% were serious. The events included self-limiting gastrointestinal complaints, infection, abdominal pain, worsening of ulcerative colitis, bloating, and fever.
Chen et al.⁹	Open-label prospective trial	UC	9	Colonoscopy FMT by NJT or TET	Clinical remission 55.6% at week 12 and endoscopic remission 33.3% at week 12	Mild and self-limiting AEs in 33.3% including mild abdominal pain, diarrhea, and fatigue, all of which were self-limiting
Chen et al.¹⁰	Single-arm pilot clinical trial	UC	21	Capsulized FMT	Clinical remission of 57.1% (12/21) at week 12	Mild gastrointestinal complaints, no serious AEs.
Costello et al.¹¹	Randomized controlled trial	UC	73	FMT via colonoscopy	Clinical remission of 32% (12/38) at week 8 for donor FMT vs 9% (3/35) for autologous FMT	Serious AEs occurred in 3 donor FMT group (worsening colitis, Clostridium difficile colitis requiring colectomy, and pneumonia) and 2 in the autologous FMT group (both worsening colitis)
Fang et al.¹²	Prospective randomized pilot study	UC	20 (FMT: 10; Control: 10)	FMT via colonoscopy	90% (9/10) achieved remission at week 8; 62.5% (5/8) maintained remission at 24 months.	AEs included mild abdominal pain, bloating, nausea; EBV infection within 2 weeks post-FMT; no other serious AEs during long-term follow-up.
Jacob et al.¹³	Prospective open-label pilot study	UC	20	FMT via colonoscopy	Clinical remission 15% (3/20) at week 4	No serious Ads including fever, abdominal pain, and diarrhea.
Kedia et al.¹⁴	Randomized control trial	UC	73	FMT via colonoscopy, and anti-inflammatory diet (Nutrition)	At week 8: 60% (FMT-AID)	No serious AEs reported with common event including mild abdominal pain, bloating, diarrhea, and worsening of disease.
Lahtinen et al.¹⁵	Randomized controlled trial	UC	48	Single dose FMT or autologous transplant via colonoscopy	54% in FMT group, at 12 months	AEs infrequent, mild, and distributed equally between the groups, and included fatigue, gastroenteritis, and constipation.
Mizuno et al.¹⁶	Single-arm, open-label, non-randomized study	UC	10	FMT via colonoscopy	Not specified	No severe AEs reported.
Nishida et al.¹⁷	Single-center open-label single-arm study	UC	41	FMT via colonoscopy	Not specified	No AEs reported for 8 weeks.
Paramsothy et al.¹⁸	Randomized, double-blind, placebo-controlled trial	UC	81 patients (FMT n = 41; placebo n = 40)	FMT via colonoscopy	27% achieved clinical remission with endoscopic remission at 8 weeks	AEs were reported by 32 (78%) of 41 patients allocated FMT most were self-limiting gastrointestinal complaints
Smith et al.¹⁹	Prospective trial	UC	20	FMT via colonoscopy	8/20 (40%) achieved remission at first follow-up (week 6);	Minor AEs included self-limited abdominal pain, constipation, diarrhea, vomiting, abdominal discomfort, excessive flatulence, and fever.
Sokol et al.²⁰	Pilot randomized controlled study	CD	17	FMT via colonoscopy	Remission of 87.5% in FMT group at week 10	13 serious AEs reported including CD flares (3 in FMT group)
Sood et al.²¹	Pilot randomized study	UC	61	FMT via colonoscopy	Clinical remission of 87.1% at week 48	No serious AEs including fever, abdominal pain, and nausea
Tikunov et al.²²	Nonrandomized pilot study	UC	20	FMT via enemas	Clinical remission of 60% at week 8	5 AEs including fever, diarrhea, and abdominal pain.
Tkach et al.²³	Randomized controlled trial	UC	53	FMT via colonoscopy	Remission of 84.6% in FMT group, at 8 weeks	No serious AEs. 7.4% in the FMT treated group. Including short-term increase in abdominal pain and bloating, diarrhea, and constipation.
Uygun et al.²⁴	Prospective and uncontrolled trial	UC	30	Colonoscopy (FMT)	Clinical and endoscopic remission of 43.3% at 12 weeks	Mild AEs in 23.3% of patients including nausea, vomiting, abdominal pain, and diarrhea.
Van Lingen et al.²⁵	Randomized control trial	UC	24	FMT engraftment	Partial remission of 42% at week 14	16 AEs including abdominal cramps and constipation.
Vaughn et al.²⁶	Prospective open-label, uncontrolled	CD	19	Single donor FMT via colonoscopy.	53% clinical remission at week 4	No serious AEs including mild GI cramping/constipation.
Wang et al.²⁷	Single center trial	CD	139	FMT via mid-gut	20% (4/20) in the patients with AE, and 63.0% (75/119) in the group without AE	13.6% experienced mild AEs within 1 week including fever, abdominal pain, flatulence, hematochezia, vomiturition, bloating, and herpes zoster.
Xiang et al.²⁸	Registered trial cohort (long term follow-up)	CD	174	FMT delivered primarily via mid-gut routes: endoscopy, nasojejunal tube, or TET	9.2% (12/131) of patients achieved sustained remission. Sustained clinical remission: 20.1% (35/174) at final follow-up	No serious AEs clearly attributed to FMT.
Yang et al.²⁹	Randomized clinical trial	CD	27	FMT via colonoscopy and gastroscopy	66.7% achieved clinical remission at week 2	Mild AEs in 76.9% of gastroscopy group and 64.3 of colonoscopy group including diarrhea, aggravation of abdominal pain, reflux, and fever.

AEs: adverse events; CD: Crohn’s disease; EBV: Epstein-Barr virus; FMT: fecal microbiota transplantation; FMT-AID: FMT with anti-inflammatory diet; NJT: Nasojejunal tube; TET: Transendoscopic enteral tube; UC: ulcerative colitis.

Intervention categories and statistics

The interventions analyzed were categorized into two groups: FMT via colonoscopy and FMT via alternative routes. Colonoscopy-based interventions, demonstrated significant efficacy in inducing clinical remission, with adverse events generally being mild and manageable as well as a safe and effective therapy for restoring gut microbiota, achieving the high remission rates, and mild gastrointestinal symptoms. Other methods, including capsules, enemas, and nasojejunal or nasoduodenal tube delivery, exhibited variable efficacy. While safety profiles were generally favorable, donor variability was identified as a significant limitation.

The analysis is summarized in Table 2. The average remission rate for FMT colonoscopy-based achieved the high average remission rate of 46.6% (41.75% for CD and 47.17 for UC), with all studies reporting adverse events. Alternative methods demonstrated an average remission rate of 58.13%, with all studies also reporting adverse events.

Table 2.

Summary of average remission rate across the different categories and diseases.

CD			UC
Category	Total studies	Average remission rate	Category	Total studies	Average remission rate
FMT via colonoscopy	5	41.75%	FMT via colonoscopy	14	47.17%
Alternative routes	0	–	Alternative routes	3	58.13%

CD: Crohn’s disease; FMT: fecal microbiota transplantation; UC: ulcerative colitis.

Remission rates

Across the included studies, FMT demonstrated variable efficacy depending on disease type and delivery approach. When stratified by intervention category, FMT administered through colonoscopy resulted in a mean remission rate of 41.75% in CD and 47.17% in UC, suggesting a modestly higher responsiveness among UC patients. In contrast, alternative delivery routes, including capsules, enemas, and nasoenteric tubes, achieved the highest average remission rate (58.13%). This variation highlights the influence of both disease phenotype and administration route on therapeutic outcomes. Overall, remission rates across categories ranged from 41.75% to 58.13%, indicating moderate heterogeneity in treatment effectiveness. The observed differences may reflect variability in study design, baseline disease severity, follow-up duration, and procedural factors rather than true differences in efficacy alone. As no statistical pooling was performed, these findings should be interpreted as descriptive trends rather than definitive comparative effectiveness.

Safety

Safety profiles of the interventions were consistently reported across the studies. Mild gastrointestinal symptoms, such as bloating, diarrhea, and cramping, were the predominant adverse events. Sporadic studies reported isolated cases of serious adverse events, including infections related to immunosuppression or procedural complications. Variability in donor microbiota composition was identified as a risk factor influencing outcomes and safety, particularly in FMT studies. Collectively, most studies indicated no significant long-term adverse events, suggesting that these interventions are well tolerated. However, safety outcomes were frequently underreported and lacked standardization, highlighting the need for more robust tracking of adverse events in future research. Adverse event definitions and severity grading varied across studies, limiting direct comparability.

Comparison of intervention categories

Despite generally favorable remission outcomes, substantial variability was observed across studies, underscoring the heterogeneous nature of FMT research in IBD. Differences in donor selection, stool preparation, frequency of administration, and pretreatment protocols likely contributed to the dispersion of remission rates. Additionally, study-level factors such as small sample sizes, open-label designs, and inconsistent definitions of clinical remission further limited comparability. While colonoscopy based FMT appeared to provide consistent remission outcomes (46.6%), alternative delivery methods showed greater variability despite higher average remission rates (58.13%). This suggests that patient selection and protocol standardization may be more influential than delivery route alone. Importantly, the reliance on descriptive statistics reflects the methodological diversity of the included studies and the inability to perform meta-analysis. Collectively, these findings emphasize the need for larger, standardized randomized trials with harmonized outcome definitions to determine the relative efficacy of FMT approaches more accurately in both UC and CD.

Risk of bias assessment

The risk of bias for the included studies was evaluated across three domains: randomization, blinding, and outcome assessment, using criteria adapted from the Cochrane Risk of Bias Tool (version 2.0; Figure 3). Of the 22 included studies, 11 were rated as low risk of bias in randomization, indicating adequate randomization processes; however, 11 studies lacked clear documentation, resulting in a high-risk rating. Blinding was effectively implemented in some studies, but a significant proportion were rated as high risk (20 studies) due to insufficient details or the absence of blinding procedures for participants, investigators, or outcome assessors. For outcome assessment, 1 study was reported as low risk using objective and consistent methods, and 16 studies were reported as moderate risk. Nevertheless, 20 studies employed subjective assessments or lacked clarity, leading to a high-risk rating. Criteria for risk-of-bias judgments are described in the “Methods” section. While many studies adhered to rigorous methodologies, limitations in blinding and outcome assessment were frequently observed, emphasizing areas for improvement in future research. These methodological weaknesses should be considered when interpreting the findings of this review. Two reviewers independently assessed risk of bias, and disagreements were resolved through discussion or consultation with a third reviewer (Figure 2).

Figure 2.

Assessment of risk of bias. Showing the risk of bias assessment for all included studies. Randomization, blinding, and outcome assessment are ranked as “low,” “high,” and “moderate” risks using criteria adapted from the Cochrane Risk of Bias Tool (version 2.0).

Potential reporting bias

A funnel plot (Figure 3) was generated to visually assess potential reporting bias, plotting effect sizes (remission rates) against their standard errors for all included studies (n = 22). Visual inspection suggested a generally symmetrical distribution, indicating a low likelihood of substantial publication bias, although minor asymmetry was observed that may reflect clinical or methodological heterogeneity or selective reporting. No formal statistical tests for small-study effects (e.g., Egger’s regression, Begg’s test) were conducted because none of the intervention categories contained at least 10 studies, which is the recommended threshold for reliable detection of asymmetry. These findings should be interpreted with caution, given the inherent subjectivity of visual assessments and the possibility of unreported outcomes in the available literature.

Figure 3.

Funnel plot representing potential reporting bias. A funnel plot showing the remission rated versus their standard errors for the 22 included studies.

Discussion

Fecal microbiota transplantation in IBD treatment

IBD poses significant health challenges, and FMT is identified as an effective treatment, outperforming probiotics. The studies were categorized into two major groups. Alternative delivery methods exhibited the highest average remission rate (58.13%), followed by FMT via colonoscopy (47.7 with UC and 41.75 with CD). These findings are consistent with other published reviews indicating FMT as a promising alternative, particularly in UC and CD, although long-term benefits remain uncertain. This highlights its effectiveness in treating CD and UC by restoring a healthy gut microbiome using donor stool. The studies also showed that FMT interventions are generally well tolerated, with favorable safety profiles. Some studies reported only mild gastrointestinal symptoms, such as bloating and cramping. However, serious adverse events, including infections related to immunosuppression, were observed in other. This underscores the importance donor selection and monitoring to minimize risks. Heterogeneity in donor microbiota composition, patient characteristics, and intervention protocols should be considered. Despite its limitations, FMT remains a promising intervention for treating IBD, particularly UC and CD.

Limitations of the evidence included in the review

The quality and generalizability of the evidence were constrained by multiple limitations (Figure 4). Randomization was poorly specified in several studies, introducing a high risk of selection bias, while unclear blinding protocols led to performance and detection bias. For instance, one study failed to adequately report blinding procedures. Subjective assessments and ill-defined outcome measures further contributed to an unclear risk of bias. Small patient cohorts restricted generalizability, and variations in donor selection, delivery methods, and antibiotic pre-treatment complicated cross-study comparisons. Short follow-up periods were common, limiting evaluation of long-term remission. Differences in donor microbiota composition added further inconsistency and hindered reproducibility. Moreover, limited research on host-microbiome interactions, and the lack of mechanistic studies, impede understanding of FMT’s mode of action. Publication bias also likely favored positive results. Finally, certainty of evidence was not graded because the review relied on descriptive synthesis rather than statistical pooling, and substantial heterogenicity across study designs, populations, interventions, and outcomes precluded a formal GRADE assessment.

Figure 4.

Bar graph showing the limitation of evidence across all included studies.

Limitations of the review processes

The review had several limitations. Only studies published in one language were included, potentially omitting relevant research. Study selection was made by individuals, introducing subjective bias. Some studies provided incomplete data, making comprehensive analysis challenging. Variations in study populations, methodologies, and outcomes created challenges in synthesizing results. The exclusion of gray literature and conference abstracts may have introduced publication bias, as studies with null or negative results are less likely to be published. Additionally, the absence of prior protocol registration limits transparency and reproducibility. Poststudy registration may have introduced bias to our results and is a limitation of this study.

Implications for practice, policy, and future research

The findings of this review have several implications. Standardizing FMT protocols would substantially enhance the reliability and reproducibility of results. Equally critical is the provision of comprehensive patient information regarding disease status and risks of FMT, thereby facilitating informed decision-making. Policy frameworks should prioritize regulatory approval and affordability of FMT to ensure equitable access. Awareness campaigns and public health initiatives may further support the education of patients and healthcare providers concerning the therapeutic role of FMT in IBD. Future research should focus on larger sample sizes to improve the generalizability of findings and long-term follow-up studies to evaluate the sustained effectiveness of FMT. Investigating the mechanism of FMT interaction with host microbiome is critical. Further comparative studies are needed to evaluate the efficacy of different FMT delivery methods and to compare FMT therapies to alternative treatment modalities. Addressing the methodological weaknesses will be essential to strengthen the evidence base.

Conclusion

FMT represents a promising therapeutic intervention for IBD, particularly in UC and CD, by restoring a healthy gut microbiome and reducing inflammation. Alternative delivery routes demonstrated the highest remission rates (58.13%), while FMT via colonoscopy also showed meaningful clinical benefit. FMT was generally well tolerated, with adverse events largely limited to mild gastrointestinal symptoms; serious events were rare but warrant careful donor selection and patient monitoring.

However, the evidence is constrained by significant heterogeneity in donor selection, delivery methods, and intervention protocols, alongside short follow-up periods and small sample sizes. The absence of prior protocol registration and restriction to English-language publications further limit generalizability. Standardized protocols, larger trials, and long-term follow-up studies are needed to consolidate the evidence base and inform clinical practice and policy.

Supplemental Material

sj-docx-1-taj-10.1177_27558428261449952 – Supplemental material for Remission rates and safety of fecal microbiota transplantation in inflammatory bowel disease in adult patients: A systematic review

Supplemental material, sj-docx-1-taj-10.1177_27558428261449952 for Remission rates and safety of fecal microbiota transplantation in inflammatory bowel disease in adult patients: A systematic review by Othman Alharoun, Nourelhoda Abdo, Sarah Dimassi, Teddy Kanbar, Kawthar Ossaily, Sally Tahhan, Jimmy Bou Saba, Mariline Al Kazzi, Aia Sinno and Charbel Al Khoury in Sage Open Chronic Disease

Supplemental Material

sj-docx-2-taj-10.1177_27558428261449952 – Supplemental material for Remission rates and safety of fecal microbiota transplantation in inflammatory bowel disease in adult patients: A systematic review

Supplemental material, sj-docx-2-taj-10.1177_27558428261449952 for Remission rates and safety of fecal microbiota transplantation in inflammatory bowel disease in adult patients: A systematic review by Othman Alharoun, Nourelhoda Abdo, Sarah Dimassi, Teddy Kanbar, Kawthar Ossaily, Sally Tahhan, Jimmy Bou Saba, Mariline Al Kazzi, Aia Sinno and Charbel Al Khoury in Sage Open Chronic Disease

Footnotes

Acknowledgements

We extend our sincere gratitude to Associate Editor Dr Ian Beales, Editor-in-Chief Dr Martin Krsak, and the anonymous reviewers for their valuable comments and constructive recommendations, which greatly improved the clarity and quality of this manuscript.

ORCID iDs

Sarah Dimassi

Aia Sinno

Charbel Al Khoury

Author contributions

Othman Alharoun: Conceptualization; Data curation; Formal analysis; Methodology; Visualization; Writing – original draft.

Nourelhoda Abdo: Conceptualization; Data curation; Formal analysis; Methodology; Visualization; Writing – original draft.

Sarah Dimassi: Formal analysis; Methodology; Writing – review & editing.

Teddy Kanbar: Conceptualization; Data curation; Formal analysis; Methodology; Visualization; Writing – original draft.

Kawthar Ossaily: Conceptualization; Data curation; Formal analysis; Methodology; Visualization; Writing – original draft.

Sally Tahhan: Conceptualization; Data curation; Formal analysis; Methodology; Visualization; Writing – original draft.

Jimmy Bou Saba: Investigation; Writing – review & editing.

Mariline Al Kazzi: Investigation; Writing – review & editing.

Aia Sinno: Formal analysis; Methodology; Writing – review & editing.

Charbel Al Khoury: Formal analysis; Project administration; Supervision; Validation; Writing – review & editing.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability statement

Template data collection forms extracted data from included studies, data used for analyses, and analytic code are not publicly available. However, these materials can be provided upon request by contacting the corresponding author*.

Supplemental material

Supplemental material for this article is available online.

References

Xia

Crusius

JBA

Meuwissen

SGM

, et al. Inflammatory bowel disease: definition, epidemiology, etiologic aspects, and immunogenetic studies. World J Gastroenterol 1998; 4(5): 446–458.

Eslick

GD.

Gastrointestinal diseases and their associated infections. Elsevier Health Sciences, 2019.

Ooijevaar

Terveer

Verspaget

, et al. Clinical application and potential of fecal microbiota transplantation. Annu Rev Med 2019; 70: 335–351.

Page

Moher

Bossuyt

, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021; 372: n160.

Sterne

Savović

Page

, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019.

Python Software Foundation. Python (Version 3.0) [software], https://www.python.org (2008).

The pandas development team. pandas [software]. Zenodo, https://doi.org/10.5281/zenodo.3509134 (2024).

Březina

Bajer

Wohl

, et al. Fecal microbial transplantation versus mesalamine enema for treatment of active left-sided ulcerative colitis—results of a randomized controlled trial. J Clin Med 2021; 10(13): 2753.

Chen

Liu

Zhang

, et al. Efficacy and safety of fecal microbiota transplantation by washed preparation in patients with moderate to severely active ulcerative colitis. J Dig Dis 2020; 21(11): 621–628.

10.

Chen

Fan

Zhang

, et al. Capsulized fecal microbiota transplantation induces remission in patients with ulcerative colitis by gut microbial colonization and metabolite regulation. Microbiol Spectr 2023; 11(3): e0415222.

11.

Costello

Waters

Bryant

, et al. Short duration, low intensity pooled faecal microbiota transplantation induces remission in patients with mild-moderately active ulcerative colitis: a randomised controlled trial. J Crohns Colitis 2017; 11: S23.

12.

Fang

, et al. Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study. Microb Cell Fact 2021; 20(1): 18.

13.

Jacob

Crawford

Cohen-Mekelburg

, et al. Single delivery of high-diversity fecal microbiota preparation by colonoscopy is safe and effective in increasing microbial diversity in active ulcerative colitis. Inflamm Bowel Dis 2017; 23(6): 903–911.

14.

Kedia

Virmani

Vuyyuru

, et al. Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial. Gut 2022; 71(12): 2401–2413.

15.

Lahtinen

Jalanka

Mattila

, et al. Fecal microbiota transplantation for the maintenance of remission in patients with ulcerative colitis: a randomized controlled trial. World J Gastroenterol 2023; 29(17): 2666–2678.

16.

Mizuno

Nanki

Matsuoka

, et al. Single fecal microbiota transplantation failed to change intestinal microbiota and had limited effectiveness against ulcerative colitis in Japanese patients. Intest Res 2017; 15(1): 68–74.

17.

Nishida

Imaeda

Ohno

, et al. Efficacy and safety of single fecal microbiota transplantation for Japanese patients with mild to moderately active ulcerative colitis. J Gastroenterol 2017; 52(4): 476–482.

18.

Paramsothy

Kamm

Kaakoush

, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 2017; 389(10075): 1218–1228.

19.

Smith

Piceno

Zydek

, et al. Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis. Sci Rep 2022; 12(1): 5517.

20.

Sokol

Landman

Seksik

, et al. Fecal microbiota transplantation to maintain remission in Crohn’s disease: a pilot randomized controlled study. Microbiome 2020; 8(1): 12.

21.

Sood

Mahajan

Singh

, et al. Role of faecal microbiota transplantation for maintenance of remission in patients with ulcerative colitis: a pilot study. J Crohns Colitis 2019; 13(10): 1311–1317.

22.

Tikunov

Fedorets

Shrainer

, et al. Intestinal microbiome changes and clinical outcomes of patients with ulcerative colitis after fecal microbiota transplantation. J Clin Med 2023; 12(24): 7702.

23.

Tkach

Dorofeyev

Kuzenko

, et al. Efficacy and safety of fecal microbiota transplantation via colonoscopy as add-on therapy in patients with mild-to-moderate ulcerative colitis: a randomized clinical trial. Front Med 2023; 9: 1049849.

24.

Uygun

Ozturk

Demirci

, et al. Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis. Medicine 2017; 96(16): e6479.

25.

Van Lingen

Nooij

Terveer

, et al. Faecal microbiota transplantation engraftment after budesonide or placebo in patients with active ulcerative colitis using pre-selected donors: a randomized Pilot study. J Crohns Colitis 2024; 18(9): 1381–1393.

26.

Vaughn

Vatanen

Allegretti

, et al. Increased intestinal microbial diversity following fecal microbiota transplant for active Crohn’s disease. Inflamm Bowel Dis 2016; 22(9): 2182–2190.

27.

Wang

Cui

, et al. The safety of fecal microbiota transplantation for Crohn’s disease: findings from a long-term study. Adv Ther 2018; 35(11): 1935–1944.

28.

Xiang

Ding

, et al. Efficacy of faecal microbiota transplantation in Crohn’s disease: a new target treatment? Microb Biotechnol 2020; 13(3): 760–769.

29.

Yang

Yuan

, et al. Fecal microbiota transplant via endoscopic delivering through small intestine and colon: no difference for Crohn’s disease. Dig Dis Sci 2020; 65(1): 150–157.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.26 MB

0.03 MB