Uncovering the role of microbiota and fecal microbiota transplantation in Crohn’s disease: Current advances and future hurdles

Abstract

Crohn’s disease (CD) is an idiopathic, chronic, and recurrent inflammatory condition of the gastrointestinal tract. Recent studies suggest a potential role of gut microbiota in CD, particularly dysbiosis—an imbalance in gut bacteria. While dysbiosis is consistently observed in CD, it remains uncertain whether it is a cause or a consequence of the disease. Given its association with CD, the therapeutic potential of fecal microbiota transplantation (FMT) has been explored. This review examines the role of gut microbiota in CD, evaluates the therapeutic potential of probiotics and FMT, and highlights current research findings and limitations. Key studies on the relationship between gut dysbiosis, probiotics, and FMT in CD were analyzed, with a focus on randomized trials, meta-analyses, and clinical observations. Dysbiosis is a consistent feature of CD, but its causative role remains unclear. Probiotics, prebiotics, and synbiotics have shown no efficacy in inducing or maintaining remission in CD. FMT shows potential as a therapeutic option for CD, but its efficacy remains inconsistent and inconclusive. The variability in outcomes, including diminished effects over time despite repeated FMT, underscores the need for larger, well-controlled trials. Only one randomized controlled trial (RCT) has compared FMT with sham transplantation, but the sample size was very small. Other studies are limited by factors such as small sample sizes, lack of control groups, short follow-up periods, and inconsistent methodologies, making it challenging to draw definitive conclusions. While gut dysbiosis likely plays a role in CD pathogenesis, its causative role remains uncertain. Current evidence does not support FMT as a reliable treatment for inducing or maintaining remission in CD, though it appears generally safe. Larger, standardized, RCTs are necessary to clarify the therapeutic role of FMT in CD management.

Key Words: Microbiota; Microbiome; Dysbiosis; Fecal microbiota transplantation; Crohn's disease

Core Tip: This article reviews the role of microbiota in Crohn’s disease (CD) and the effects of fecal microbiota transplantation. CD is a chronic, relapsing condition with a complex pathogenesis involving genetic and environmental factors. The gut microbiota, crucial for various bodily functions, shows dysbiosis in CD, with a reduction in beneficial microbes. This review highlights recent developments in understanding microbiota’s role in CD and its potential in treatment strategies.

INTRODUCTION

Crohn’s disease (CD) is an idiopathic, chronic, and recurring inflammatory condition affecting the gastrointestinal tract[1,2]. More than a million people worldwide are affected by CD, with its incidence climbing for reasons that are not yet fully understood. The disease tends to be more common in those over 45 years old, with no significant difference observed between genders[2].

PATHOGENESIS

The pathogenesis of CD is a multifaceted process that includes the interaction between genetic predisposition and environmental triggers, culminating in a dysregulated immune response and intestinal inflammation[3].

The study of the microbiota's role in CD is an evolving field with numerous recent developments and ongoing challenges. Dysbiosis, defined as an imbalance in gut bacteria, has been observed in CD; however, it is difficult to determine whether it is the cause or consequence of CD.

MICROBIOTA

Microbiota refers to the microorganisms in a particular environment, while the microbiome encompasses all the genetic content of those microorganisms[4]. The human gut harbors approximately 100 trillion microorganisms, representing over 1000 different species[4,5]. While bacteria constitute the majority, other microorganisms such as viruses, fungi, and protozoa are also part of the human gut microbiota[4]. The colon contains the highest concentration of microorganisms in the human body, with an estimated 3.9 × 10¹³ microbes[5]. The gut microbiota plays a specific role in the host’s nutrient and drug metabolism, maintaining the structural integrity of the gut’s mucosal barrier, modulating immune function, and defending against pathogens[6].

ROLE OF MICROBIOTA IN THE PATHOGENESIS OF CD

The study of the microbiota's role in CD is an evolving field. Dysbiosis, defined as an imbalance in gut bacteria, characterized by a reduction in beneficial microbes and an increase in potentially harmful ones. There is difficulty in distinguishing cause and effect—whether dysbiosis is a cause or a consequence of CD[5]. Patients with inflammatory bowel disease (IBD) show a decreased presence of beneficial microbes, including Clostridioides, Bacteroides, Sutterella, Roseburia, Bifidobacterium, and Faecalibacterium. Concurrently, there is an increase in harmful bacteria, including Escherichia, Salmonella, Yersinia, Desulfovibrio, Helicobacter, and Vibrio[7-9].

EFFECT ON IMMUNITY

Microbial dysbiosis seen in CD causes alterations in host immunity, leading to aberrant activation of T-helper cells and a decrease in regulatory T cells. This imbalance results in an increase in pro-inflammatory cytokines such as interleukin (IL)-6, IL-23, and tumor necrosis factor-α, which, in turn, exacerbate inflammatory response in CD patients[10-12].

ALTERATION IN MICROBIAL METABOLITES

Short-chain fatty acids (SCFAs), which are produced by intestinal microbes, are often reduced in dysbiosis due to a decline in SCFA-producing bacteria. When SCFA levels are low, their anti-inflammatory effects are diminished, which can lead to increased inflammation[13].

INTERACTION WITH HOST GENETICS

NOD2 gene mutations, commonly observed in CD patients, impair bacterial sensing and clearance. This genetic susceptibility, along with an increase in potentially harmful bacteria seen in microbial dysbiosis, contributes to an aggravated inflammatory response in CD[12].

DYSBIOSIS AND EPITHELIAL BARRIER FUNCTION

Microbial dysbiosis, by triggering an aggravated inflammatory response, leads to increased intestinal permeability due to the disruption of the epithelial barrier. This increases susceptibility to harmful or pro-inflammatory bacteria, further exacerbating the inflammatory response in CD[14].

The gut microbiota seems to play an important role in the pathogenesis of CD. Dysbiosis could lead to inappropriate interactions with the intestinal innate immunity, causing a cascade of host-microbe reactions that trigger an inflammatory response in genetically susceptible patients.

Ma et al[13] studied the role of dysbiosis in gut microbiota in early CD and its impact on the progression of the disease. The study included 18 early CD patients, 22 advanced CD, and 30 healthy control individuals. The study found elevated levels of Lachnospiraceae incertae sedis and Parabacteroides in early CD, whereas Escherichia/Shigella, Enterococcus, and Proteus were more prevalent in advanced cases. In contrast, healthy individuals exhibited higher levels of Roseburia, Gemmiger, Coprococcus, Ruminococcus, Butyricicoccus, Dorea, Fusicatenibacter, Anaerostipes, and Clostridioides. The study also revealed that microorganisms such as Blautia, Clostridioides, Coprococcus, Dorea, and Fusicatenibacter progressively declined with the progression of CD, while Escherichia/Shigella and Proteus levels steadily increased. The study highlighted that the steady decline in SCFA-producing bacteria as CD progresses significantly disrupts the integrity of the intestinal epithelium and promotes inflammation. Furthermore, the increase in harmful microbes exacerbates gut dysbiosis, thereby contributing to disease progression.

Zhou and Zhi’s meta-analysis, which included 9 studies involving 706 patients, examined the relationship between Bacteroides levels and CD[9]. The analysis found that Bacteroides levels were significantly lower in patients with active CD compared to healthy controls. Although Bacteroides levels were also reduced in patients with CD who were in remission compared to controls, the levels remained lower in those with active disease[9].

Gevers et al[15] investigated the relationship between microbiota and CD in children aged 3 to 17 years, including 447 patients with CD and 221 healthy controls. The study found that, overall, microbiome diversity did not differ significantly between CD patients and healthy controls. However, specific microbes were positively correlated with CD activity. Notably, Enterobacteriaceae, Bacteroidales, Clostridioides, Pasteurellaceae (including Haemophilus spp.), Veillonellaceae, Neisseriaceae, and Fusobacteriaceae showed a positive correlation with disease severity. Additionally, the study found that CD negatively correlated with certain microbes, such as Bacteroides, Faecalibacterium, Roseburia, Blautia, Ruminococcus, Coprococcus, and the families Ruminococcaceae and Lachnospiraceae. The study also compared the microbiomes of CD patients with and without antibiotic exposure and found that antibiotics aggravated microbial dysbiosis.

Prosberg et al[16] conducted a meta-analysis that included 3 prospective and 7 cross-sectional studies to examine the association between microbiota and IBD activity. 5 studies included 231 patients with CD. The authors found that IBD patients exhibit a distinct gut microbiota profile compared to healthy individuals, characterized by reduced diversity and alterations in specific bacterial taxa. Notably, their findings revealed that patients with CD had reduced levels of Clostridioides, Faecalibacterium prausnitzii, and Bifidobacterium. These microbial shifts were associated with disease activity, suggesting that gut microbiota composition may influence CD pathogenesis and could serve as a potential biomarker for disease activity.

The findings of the above-mentioned studies are summarized in Table 1.

Table 1 Gut microbiota in Crohn’s disease.

Ref.	Participants	Key findings
Ma et al[13]	Prospective cohort study (18 early CD, 22 advanced CD, 30 healthy control)	Elevated levels of Lachnospiraceae incertae sedis and Parabacteroides in early CD. Escherichia/Shigella, Enterococcus, and Proteus were more prevalent in advanced cases. Higher levels of Roseburia, Gemmiger, Coprococcus, Ruminococcus, Butyricicoccus, Dorea, Fusicatenibacter, Anaerostipes, and Clostridioides. Steady decline in short chain fatty acid-producing bacteria as CD progresses
Zhou et al[9]	Meta-analysis (9 studies with 706 patients)	Bacteroides levels were significantly lower in patients with active CD compared to healthy controls. Reduced levels of Bacteroides were associated with CD activity
Gevers et al[15]	Observational case-control study (447 patients with CD, 221 healthy control)	Enterobacteriaceae, Bacteroidales, Clostridioides, Pasteurellaceae (including Haemophilus spp.), Veillonellaceae, Neisseriaceae, and Fusobacteriaceae showed a positive correlation with CD severity. Bacteroides, Faecalibacterium, Roseburia, Blautia, Ruminococcus, Coprococcus, and the families Ruminococcaceae and Lachnospiraceae negatively correlated with CD. Dysbiosis observed in CD patients. Antibiotics aggravated microbial dysbiosis
Prosberg et al[16]	Meta-analysis. Total 10 studies including CD and ulcerative colitis. 5 studies with 231 CD patients.	Reduced levels of Clostridioides, Faecalibacterium prausnitzii, and Bifidobacterium in CD patients. Dysbiosis may be involved in the activity of IBD

CD: Crohn’s disease; IBD: Inflammatory bowel disease.

ROLE OF PROBIOTICS

Since intestinal microbial dysbiosis is thought to play a role in the development of CD, the roles of probiotics, prebiotics and postbiotics in the treatment of CD have been investigated. Probiotics are live microorganisms that provide health benefits, prebiotics are nutrients that nourish these beneficial microbes, and postbiotics are health-promoting substances produced by probiotics[17]. In a review by Ma et al[18], which analyzed 53 clinical trials on probiotics/prebiotics, and synbiotics (mixture of probiotics) in IBD, 5 studies focused on inducing remission in active CD, with mixed results and only mild benefits observed. Ten additional studies assessed the role of probiotics in maintaining remission, most of which found them ineffective. The review concluded that current evidence did not support the use of probiotics for either induction or maintenance of remission in CD[18].

ROLE OF PROBIOTICS IN INDUCING REMISSION IN CD

Gupta et al[19] reported that 4 children with mild to moderate CD showed significant improvement in clinical activity with the use of probiotics. However, their study lacked a control group and had a very small sample size.

Schultz et al’s double-blinded randomized controlled trial (RCT) included 5 CD patients who received probiotics and 6 CD patients in the control group. They reported no beneficial effects of probiotics[20].

Fujimori et al[21] reported a decrease in CD Activity Index (CDAI) with the use of probiotics in 10 CD patients. However, their study did not include a control group.

Steed et al’s double-blinded RCT included 13 patients in the probiotics treatment group and 11 in the control group[22]. They reported a significant decrease in CDAI with the use of probiotics.

The findings of the above-mentioned studies are summarized in Table 2.

Table 2 Role of probiotics in inducing remission in Crohn’s disease.

Ref.	Type of study	Number (n)	Findings
Gupta et al[19]	Open label	4 CD patients. No control group	Improvement in clinical activity
Schultz et al[20]	DB RCT	Treatment group (n = 5). Control group (n = 6)	No benefits of probiotics
Fujimori et al[21]	Open label	10 CD patients. No control group	Decrease in CDAI
Steed et al[22]	DB RCT	Treatment group (n = 13). Control group (n = 11)	Decrease in CDAI

CD: Crohn’s disease; DB: Double blind; RCT: Randomized controlled trial; CDAI: Crohn’s disease activity index.

The studies showed some benefits of probiotics in CD; however, the lack of control groups and the small sample sizes in most studies are significant limitations. Therefore, more placebo-controlled trials are needed before probiotics can be recommended for inducing remission in CD.

PROBIOTICS IN THE MAINTENANCE OF REMISSION IN CD

Garcia et al’s RCT included 14 CD patients who received probiotics and 17 CD patients in the control group[23]. They reported improved intestinal permeability in CD patients in remission with the use of probiotics.

Bourreille et al’s double-blinded RCT, which included 80 CD patients in the treatment group and 79 in the control group, did not find any beneficial effects of probiotics[24].

Bjarnason et al’s RCT also did not show any beneficial effects of probiotics[25]. Their study included 33 CD patients in the treatment group and 29 in the control group.

Marteau et al’s double-blinded RCT, which included 48 CD patients in the treatment group and 50 in the control group, did not find any beneficial effects of probiotics[26].

The findings of the above-mentioned studies are summarized in Table 3.

Table 3 Role of probiotics in the maintenance of remission in Crohn’s disease.

Ref.	Type of study	Number (n)	Findings
Garcia et al[23]	RCT	Treatment group (n = 14). Control group (n = 17)	Improvement in clinical activity
Bourreille et al[24]	DB-RCT	Treatment group (n = 80). Control group (n = 79)	No benefits of probiotics
Bjarnason et al[25]	RCT	Treatment group (n = 33). Control group (n = 29)	No benefits of probiotics
Marteau et al[26]	DB RCT	Treatment group (n = 48). Control group (n = 50)	No benefits of probiotics

DB: Double blind; RCT: Randomized controlled trial.

The results of these clinical trials on probiotics for CD have demonstrated either ineffectiveness or inconsistent outcomes.

ROLE OF FECAL MICROBIOTA TRANSPLANTATION

Wu et al's study demonstrated the positive effects of fecal microbiota transplantation (FMT) in animal models[27]. They explored the effects of FMT in a mouse model of CD induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Fecal microbiota was collected from both CD patients and healthy controls and then transplanted into TNBS-induced CD mice. The study found that FMT from healthy donors improved CD symptoms, whereas FMT from CD patients exacerbated them. FMT also influenced inflammatory cytokines, such as IL-6, IL-1β, tumor necrosis factor-α, interferon-𝛾, macrophage chemotactic protein-1, leptin, and adiponectin, in the serum, colon, and mesenteric adipose tissue. These levels worsened with FMT from CD patients but improved with FMT from healthy controls[27]. While this study demonstrated the positive effects of FMT in an animal model, evidence supporting its use for treating CD in humans remains insufficient.

A 2023 Cochrane review examined 12 studies involving 550 participants to assess the role of FMT in IBD[28]. None of these studies specifically evaluated FMT for inducing remission in active CD. Only one study, by Sokol et al[29], which included 17 patients, explored the use of FMT for maintaining remission in CD. In this study, 17 patients were included: 8 received FMT, and 9 underwent sham transplantation. Prior to the transplantation, all patients were treated with corticosteroids to induce remission of their acute flare-ups. The study found that none of the patients achieved more than 60% similarity with the donor microbiota after transplantation, indicating limited engraftment of the donor microbiota. Over the course of the study, there were 9 CD flares—6 in the sham group and 3 in the FMT group. Although the incidence of acute flares was lower in the FMT group, the difference was not statistically significant. However, a significant benefit of FMT over sham was observed in terms of CD Endoscopic Index of Severity (CDEIS) and C-reactive protein (CRP) levels. The FMT group showed a greater decrease in CDEIS compared to the sham group, and while CRP levels increased in the sham group, the FMT group did not show any increase in CRP[29]. A limitation of these findings was that the CDEIS in the sham group was already quite low at baseline, making it challenging to observe a significant further drop. As a result, no definitive conclusions could be drawn regarding the effectiveness of FMT in maintaining remission in CD.

In another clinical trial, He et al[30] investigated the role of multiple FMTs in inducing and maintaining clinical remission in CD complicated by inflammatory masses. The study included 25 patients with CD and inflammatory masses. Of these, 76% had ileum and colon involvement, 12% had ileal involvement, and 12% had colon involvement. After the first FMT, subsequent FMTs were administered at 3-month intervals. The primary route of administration was esophagogastroduodenoscopy to the duodenum, used in 23 of the 25 patients, while 2 patients received FMT via a tube inserted into the cecum during a colonoscopy. The initial FMT induced remission in 52% of patients. The proportion of patients achieving sustained clinical remission with repeated FMTs decreased over time: 48% at 6 months, 32% at 12 months, and 22.7% at 18 months. These findings suggest that while FMT demonstrated some efficacy in inducing clinical remission, its effect diminished despite repeated administrations. The study had several limitations, including the lack of a control group, small sample size, and the absence of endoscopic evaluation in any patient. Despite these limitations, the trial offered useful insights into the limited potential of FMT in treating complex CD cases.

In a study by Suskind et al[31], the role of FMT in active CD was investigated. The trial included 9 patients with active CD of mild to moderate severity, based on a Pediatric CDAI (PCDAI) score of 10–29. Prior to FMT, all patients were treated with rifaximin for 3 days and Miralax for 2 days. The FMT was administered via a nasogastric tube. Among the participants, only one patient had disease localized to the colon, while the remaining patients had multiple gastrointestinal sites affected, including the esophagus, stomach, duodenum, terminal ileum, and colon. Metagenomic sequencing revealed successful engraftment of donor microbiota in 7 out of 9 patients. At the 2-week follow-up, 7 out of 9 patients achieved clinical remission, and 5 out of 9 patients sustained remission at both 6 weeks and 12 weeks. Clinical response was measured by a significant decrease in PCDAI scores, which dropped from a baseline of 19.7 ± 7.2 to 6.4 ± 6.6 at 2 weeks and 8.6 ± 4.9 at 6 weeks. Minimal or no improvement was observed in patients who did not achieve successful microbiota engraftment. While the study demonstrated potential benefits of FMT in managing active CD, it had several limitations, including the lack of a control group, small sample size, and the inclusion of antibiotics and laxatives prior to FMT, which may have influenced the outcomes. Additionally, the continuation of CD medications such as immunomodulators after FMT acted as a confounding factor in assessing the independent effect of FMT.

Wang et al[32] investigated the safety of FMT in patients with CD and found it to be a generally safe option. Among 139 patients who underwent a total of 184 FMTs with naso-jejunal tube or gastroscopic infusion, adverse effects were observed in 13.6% of patients. These adverse effects included increased frequency of defecation, mild abdominal pain, flatulence, hematochezia, and bloating, all of which occurred within the first month following FMT. No adverse effects were reported after the one-month mark. One patient developed herpes zoster, which was self-limiting. Of the 25 recorded adverse events, 84% (21/25) resolved without any treatment, while 16% (4/25) required medications. One patient required steroids due to persistent fever and was deemed to have experienced a failed FMT accompanied by a CD flare-up. The study also found a significant association between the method of fecal microbiota preparation and the occurrence of adverse effects. Patients who underwent manual methods of preparation had an adverse effect rate of 21.7%, compared to 8.7% for those who received FMT prepared using automated machine-operated purification methods. Despite this difference, the clinical remission rate was 56%, with no significant variation between the two preparation methods. Overall, the study concluded that FMT is a safe and effective treatment option for CD, with a reasonable clinical remission rate and manageable adverse effects.

Xiang et al[33] conducted a study involving 174 patients with CD to evaluate the efficacy of FMT, focusing on symptom improvement as the primary outcome. Most patients received FMT via mid-gut delivery methods, including endoscopy, naso-jejunal tubes, or transendoscopic enteral tubing. Only one patient underwent FMT via colonoscopy. The follow-up duration was 43 months. 109 patients received multiple FMTs. Overall, 43% of patients (76/174) showed a positive clinical response, and 20.1% (35/174) achieved sustained clinical remission. The study also observed that frozen FMT was associated with an 11.3% decrease in clinical response compared to fresh FMT, although the exact number of patients who received frozen FMT was not specified. Key limitations of the study included the absence of a control group, as well as the lack of biomarkers or endoscopic findings as objective targets for assessing treatment efficacy.

Yang et al's RCT assessed the efficacy of FMT, comparing colonoscopy and gastroscopy as delivery methods[34]. 14 patients received FMT via colonoscopy, and 13 via gastroscopy, with a second FMT administered one week after the first. Clinical evaluations and serum testing to calculate the CDAI were performed at weeks 1, 2, 4, 6, and 8, with endoscopic evaluations conducted at week 8. Clinical remission was achieved in 66.7% (18/27) of patients, with no significant difference between the colonoscopy (64.3%) and gastroscopy (69.2%) groups. The overall clinical response rate was 77.8% (21/27), again showing no difference between the colonoscopy (78.6%) and gastroscopy (76.9%) groups. Notably, none of the patients achieved endoscopic remission at 8 weeks. Diarrhea was the most common adverse effect, occurring more frequently in the colonoscopy group (57.1%) compared to the gastroscopy group (14.3%). Aggravation of abdominal pain was reported in 21.4% of patients in the gastroscopy group and 14.3% in the colonoscopy group. Most adverse events resolved spontaneously within 24 hours. The study also found that clinical remission was more frequent in patients who received FMT from a related donor (73.7%, 14/19) compared to those who received FMT from unrelated donors (50%, 4/8), although this difference was not statistically significant. Key limitations of the study included a short follow-up duration and the absence of a control group without FMT treatment.

The findings of the above-mentioned studies are summarized in Table 4.

Table 4 Role of fecal microbiota transplantation in Crohn’s disease.

Ref.	Type of study	Participants	Findings	Conclusion
Sokol et al[29]	RCT	8 received FMT. 9 received sham transplantation	Flare-up in 3/8 in FMT group. Flare-up in 6/9 in sham group. Higher decrease in CDEIS in FMT group	Difference in flare-up was not statistically significant. Limitations: Small sample size; low baseline CDEIS sham group
He et al[30]	Prospective cohort study	25 CD patients received multiple FMTs at 3-month interval. No control group	Remission induced in 52%. Sustained remission decreased overtime: 48% at 6 months. 32% at 12 months. 22.7% at 18 months	Some efficacy in inducing clinical remission. Effect diminished despite repeated administrations. Limitations: Lack of control group, small sample size, absence of endoscopic evaluation
Suskind et al[31]	Open label study	9 CD patients. No control group	7/9 achieved remission at 2 weeks. 5/9 showed persistent remission after 6 and 12 weeks	Potential benefits of FMT. Limitations: No control group, small sample size. Inclusion of antibiotics. Continuation of immunomodulators after FMT
Wang et al[32]	Prospective cohort study	139 CD patients. No control group	Remission in 56%. Adverse effects (AE) in 13.6% (25/139). AE in 84% resolved without treatment. AE in 16% needed medications. AE rate 217% in manual FMT preparation group vs 8.7% in automated machine-operated group	FMT generally safe. Automated purification method safer than manual method. Reasonable remission rate
Xiang et al[33]	Prospective cohort study	174 CD patients. No control group	43% achieved clinical remission. Sustained remission in 20.1% at 43 months. Frozen FMT showed 11.3% lower response compared to fresh FMT	Potential benefits of FMT in CD patients. Limitations: No control group. Lack of biomarkers. Lack of endoscopic findings
Yang et al[34]	Prospective cohort study	27 CD patients 14 received FMT via colonoscopy and 13 via gastroscopy. No control group. Follow-up period – 8 weeks	Clinical remission in 66.7%. No difference between colonoscopy (64.3) vs gastroscopy (69.2%) group. Clinical response in 77.8%. No difference between colonoscopy (78.6) vs gastroscopy (76.9%) group	Potential benefits of FMT. Limitations: No control group. Short follow-up period

RCT: Randomized controlled trial; FMT: Fecal microbiota transplantation; CDEIS: Crohn’s disease endoscopic index of severity; CD: Crohn’s disease; AE: Adverse effect.

In the latest American Gastroenterology Association (AGA) clinical practice guideline on fecal microbiota-based therapies for select gastrointestinal diseases, the AGA advises against the use of conventional FMT for treating IBD, except as a part of a clinical trial[35].

Current evidence highlights the potential of FMT as a therapeutic option for CD, but its efficacy remains inconsistent and inconclusive. While some studies demonstrate promising clinical responses and remission rates, limitations such as small sample sizes, lack of control groups, short follow-up periods, and inconsistent methodologies hinder definitive conclusions. The variability in outcomes, including the diminished effects of repeated FMT and the inconsistent microbiota engraftment, underscores the need for standardized protocols and larger, well-controlled trials.

CONCLUSION

Multiple studies suggest a role for dysbiosis in gut microbiota in CD, but it remains unclear whether dysbiosis is a cause or consequence of the disease. FMT shows some promise as a therapeutic option for CD, with some studies reporting improved clinical responses and reduced disease activity. However, the evidence is limited by small sample sizes, methodological inconsistencies, and short follow-up periods. The variability in outcomes, including inconsistent microbiota engraftment and diminishing effects with repeated treatments, highlights the need for caution. Large-scale, RCTs are necessary to establish clear guidelines for FMT in CD treatment, including standardized protocols for delivery methods, donor selection, and follow-up duration. Further research is needed to understand the mechanisms behind FMT’s effects and to identify biomarkers that can predict patient responses. While FMT may serve as a potential adjunctive therapy for managing CD, its widespread use cannot be recommended until more robust evidence is available to support its safety and efficacy.