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

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.

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.

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.

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.