IBS is a prevalent gastrointestinal disorder that significantly impacts patients' quality of life and imposes substantial economic burdens globally [34, 35]. Recent research has delved into the potential of microbiota-targeting treatments for IBS sufferers [36]. The rationale behind these interventions hinges on the direct influence of microbiota on the gut’s mucosal environment and their regulatory impact on the gut–brain communication pathway [36], aiming to preserve gut mucosal integrity, alter gut microbiome composition and mitigate inflammatory cytokine release [37, 38]. However, the definitive effectiveness and safety of FMT in IBS patients remain inconclusive.

To address this gap, our study performed a comprehensive systematic review and meta-analysis to explore the efficacy and safety of FMT in patients with IBS. We included updated studies and eventually identified 12 RCTs. In addition, we combined various scoring systems in IBS-QOL by using SMD while considering the changes in IBS-SSS and IBS-QOL scores from the baseline. We further strengthened our analysis by applying the rigorous TSA method to test the robustness of our findings. As a result, our study provides a highly reliable and insightful perspective on the effectiveness of FMT in IBS treatment.

Consistent with the meta-analyses published recently in 2022 and 2023, our study revealed no significant differences between the FMT and control groups in terms of clinical responses after 12 weeks [23, 24, 26, 39]. A similar result was shown in terms of the changes in IBS-SSS and IBS-QOL after 8–12 weeks. We also observed high heterogeneity amongst studies, suggesting that caution is needed in interpreting results. No serious adverse events were related to FMT in IBS. The GRADE assessments indicated that the CoE for all clinical outcomes in our study was very low.

Various delivery routes are currently utilised for FMT. They include oesophagogastroduodenoscopy; nasogastric, nasojejunal or nasoduodenal tube; colonoscopy; rectal enema and oral capsule delivery. Our subgroup analyses revealed that the route of FMT delivery significantly influenced its efficacy. FMT delivered via routes with more direct delivery to the gut, such as endoscopy, nasojejunal tube, or rectal enema, significantly improved all three outcomes, including clinical response, change in IBS-SSS and change in IBS-QOL compared to control. In contrast, oral capsule FMT did not demonstrate any benefits, suggesting that direct delivery to the target site may be more effective. Several biological and physiological factors may explain the superiority of direct delivery routes. Firstly, the live bacterial counts of FMT capsules range widely from 100 million bacteria per capsule to 100 billion bacteria per capsule and decline rapidly over time, reaching only 10% of their initial values after 24 hours [40]. This rapid decline in bacterial viability can significantly impact the effectiveness of the treatment. Secondly, the capsules expose bacteria to harsh gastric conditions, reducing bacterial viability and colonisation potential in the gut [41, 42]. Direct delivery methods like endoscopic, nasojejunal and rectal enema bypass the stomach, allowing for better survival and engraftment of the transplanted microbiota. [43] Thirdly, the gastrointestinal tract, particularly the lower intestines, is an anaerobic environment. Many of the beneficial gut microorganisms, such as obligate anaerobes, are highly sensitive to oxygen exposure [44]. Oral capsules may expose these anaerobic microorganisms to oxygen during transit through the upper gastrointestinal tract, potentially compromising their viability and functionality. Direct delivery minimises exposure to oxygen, maintaining the anaerobic environment necessary for these microorganisms to thrive. [45] Lastly, deviations from recommended protocols, such as using suboptimal doses or improper storage conditions, may have decreased the efficacy of oral capsule FMT in some studies. As noted previously by Rodrigues et al. [39] the recommended dose for a faecal transplant is 30 g. However, Aroniadis et al. administered less than the recommended dose. [14] In addition, Halkjaer et al. stored their final faecal suspensions at − 20 °C [11], whereas guidelines suggest storage at − 80 °C [46]. These deviations from the recommended protocol may have decreased the efficacy of oral capsule FMT, thereby diminishing the overall pooled effect of its efficacy.

Another emerging way to deliver FMT is colonic transendoscopic enteral tubing (TET), which has shown potential in treating various gut disorders, including IBS [47]. This procedure involves inserting a long, soft tube through the rectum into the colon using a colonoscope to infuse the faecal suspension directly into the colonic region. This tube allows for targeted infusion of the faecal suspension throughout the colonic region [47]. Compared to traditional colonoscopic delivery, TET is less invasive, better tolerated by patients and eliminates the need for full colon preparation [47]. Growing evidence suggests that administering FMT through a colonic TET could serve as a promising and more patient-friendly treatment strategy for patients with inflammatory bowel disease [47]. A recent prospective observational study by Zhang et al. demonstrated that washed microbiota transplantation delivered via mid-gut TET in 12 patients (16.4%) and colonic TET in 61 patients (83%) effectively improved both gastrointestinal and extraintestinal symptoms in individuals with IBS [48]. Despite these promising findings, further research through rigorous clinical trials specifically evaluating colonic TET-delivered FMT for IBS treatment is necessary.

The quality of the pooled studies could affect the reported effectiveness of FMT treatment. In our study, subgroup analysis based on overall RoB showed that in studies with a low RoB, the patients who received FMT had a significant improvement in all clinical outcomes, suggesting that methodological rigour is crucial in evaluating the true efficacy of FMT. Potential biases like inadequate allocation concealment, lack of blinding and high dropout rates may have obscured true effects in lower-quality studies. Further large-scale, high-quality RCTs are warranted to confirm the therapeutic role of FMT in the management of IBS.

Our study also analysed the effect of different faecal origins on FMT and its efficacy in patients with IBS. The results of subgroup analysis did not reveal a significant clinical response to FMT samples from single or mixed donors and in patients who received FMT using fresh, frozen or mixed stool samples. However, due to the limited sample size of our study, further research is needed to reach a conclusion on the preferable type of faeces.

The present study has several limitations. One major limitation is the heterogeneity of the enrolled participants, which persisted even after extensive subgroup analyses. This heterogeneity can be attributed to several factors. Firstly, the enrolled participants exhibited high heterogeneity, with variations in the diagnostic criteria employed IBS as well as the specific IBS subtypes represented. These RCTs included participants with different IBS subtypes (IBS-C, IBS-D, IBS-M, IBS-U) and most of the RCTs included a mixture of patients with differing IBS subtypes, which may respond differently to FMT due to varying underlying pathophysiologies. This variation makes it challenging to determine whether FMT efficacy differs among IBS subtypes. Future studies should focus on specific IBS subtypes to identify patient populations most likely to benefit from FMT.

Secondly, the inclusion criteria for symptom severity varied across studies. Some included participants with more severe IBS symptoms (e.g. IBS Symptom Severity Score (IBS-SSS) ≥ 175) [11, 12, 14, 15, 20], while others did not specify symptom severity criteria, potentially leading to differences in treatment response [13, 16, 18, 19, 21]. Furthermore, utilising different diagnostic criteria, Rome IV versus Rome III, leads to the inclusion of distinct patient populations with varying disease severities, as Rome IV criteria tend to identify individuals with a more severe clinical presentation of IBS [48, 49]. This discrepancy in the recruited cohorts based on diagnostic criteria introduces a fundamental difference in the study populations, complicating the interpretation and comparison of treatment outcomes across studies. Future studies should focus on implementing standardised symptom severity criteria and unified diagnostic standards (preferably Rome IV) across all trials. Studies are recommended to incorporate pre-planned subgroup and sensitivity analyses to evaluate the impact of different inclusion criteria on outcomes.

Thirdly, the FMT interventions differed in terms of their origin, dosage, therapy duration, frequency, comparators and study protocols, making it difficult to analyse and compare the results. The dosages of donor stool ranged from 25 capsules (50g) to a single dose of 30-80g, and the frequency of administration varied from a single dose to multiple doses over several days. The placebo interventions varied across studies, with some using autologous stool transplantation and others using inert capsules or solutions. These variations may differently impact the gut microbiota, placebo response and the relative efficacy of FMT. Additionally, several studies lacked clear reporting of the inclusion and exclusion criteria used for donor selection, which may limit the generalisability of the findings. To enhance consistency and reproducibility, future trials should adopt a comprehensive, standardised protocol that includes donor screening and selection, FMT dosage, frequency, duration and placebo interventions, all guided by the latest consensus statements on best practices for FMT [50,51,52].

The heterogeneity observed in our meta-analysis, arising from the diverse features discussed, underscores the complex and multifaceted nature of both IBS and FMT as a therapeutic intervention. Although this heterogeneity limits the robustness of our conclusions, it also offers valuable insights into the factors that may influence the efficacy of FMT in treating IBS.

Another limitation of our study is that the included RCTs primarily focused on gut-specific symptoms like abdominal pain, bloating and bowel habits (i.e. IBS-SSS) and their impacts on quality of life (i.e. IBS-QOL). However, it’s crucial to recognise that IBS is a multifaceted condition that affects more than just the gastrointestinal system, and these broader effects can significantly impair a patient’s quality of life [53]. Psychological distress, including anxiety and depression, is common among IBS patients, influencing various aspects like gut physiology and immune response through the gut–brain axis [54]. Unfortunately, most RCTs do not adequately capture these outcomes, leading to a high degree of variability among studies that do include them. Guo et al. focused on patients with IBS-D who also suffered from depression and anxiety [18]. Their findings revealed that FMT therapy reduced not only gastrointestinal symptoms but also anxiety and depression. [18] Conversely, studies by Aroniadis et al., Mazzawi et al., Holster et al. and Lahtinen et al. reported no significant effect of FMT on depression and anxiety [13, 14, 16, 19]. Notably, Mazzawi et al. and Lahtinen et al. did not provide baseline data on depression and anxiety [16, 19], and Holster et al. explicitly excluded patients with depression prior to intervention [13]. Factors like concurrent psychological disorders, diet variations, co-medications and follow-up care are often overlooked in current RCTs, potentially limiting the efficacy evaluation of FMT for IBS [55]. Future research should adopt a comprehensive approach, including standardised tools to assess not only gastrointestinal symptoms but also psychological health and other relevant outcomes.

Despite these limitations, our study provides valuable insights into the effectiveness of FMT for IBS treatment. While the overall pooled estimates did not show a significant benefit of FMT, the subgroup analyses suggest that FMT, particularly when delivered via endoscopy, nasojejunal tube, or rectal enema, and in well-designed studies, may be an effective treatment option for improving symptoms and quality of life in IBS patients. However, the certainty of evidence was rated as “very low” due to concerns about bias, heterogeneity and imprecision, indicating limited confidence in the effect estimates. The true effect may differ from the estimates presented in our meta-analysis. Although the TSA results for the most important outcome, clinical response, suggest that the current evidence is a true positive, the sample size remains insufficient to draw a definitive conclusion. This inadequacy in sample size leads to a downgrade in the GRADE assessment in the domain of imprecision. Further well-designed studies with more participants should strive to standardise study designs, donor screening, treatment protocols, outcome metrics and the stratification of participants by IBS subtype to enhance the consistency and applicability of FMT research in IBS. It is imperative to explore potential effect modifiers through pre-specified subgroup analyses and meta-regression, as well as to examine the long-term effects and safety of FMT, to effectively integrate these findings into clinical practice.