To the Editor: We read with great interest Pigneur and Sokol’s review article1 about fecal microbiota transplantation (FMT) and its challenges in treating inflammatory bowel disease (IBD). As highlighted by the authors, one of the major factors that may optimize FMT for IBD is how the recipient’s bowel is prepared prior to an FMT. Theoretically, using antibiotics has the potential to “make space for the new microbiota” before FMT by freeing previously occupied niches. Recently, Ishikawa et al.2 showed that administration of amoxicillin, fosfomycin, and metronidazole for 2 weeks prior to FMT improved bacterial dysbiosis in ulcerative colitis (UC) patients through transplantation of Bacteroidetes from donors in comparison to no pretreatment prior to FMT.
In order to investigate how the administration of antibiotics before FMT affects the outcome (clinical remission) in adult UC patients, we performed a meta-analysis of previously published studies. Our search strategy was similar to the one used in Colman and Rubin’s recent systematic review,3 and we only included studies that were performed on adult UC patients. Comprehensive Meta-analysis, V.3 (Biostat, Englewood, NJ, USA) was used for statistical analysis. Overall effect (clinical remission rate in UC) was derived from the random effect model using the DerSimonian and Laird method, which takes between-study variation into account. Between-subgroup heterogeneity (antibiotics vs. no-antibiotics pretreatment) was assessed using the fixed-effect model.
In total, nine studies (118 patients) were selected for this analysis. Two studies4, 5 were randomized controlled trials and we only included data from their FMT arms. The pooled remission rate following FMT in UC was 30.3% (95% confidence interval (CI)=19.3–44.2%). As shown in Figure 1, the remission rate after FMT was significantly higher in studies that used antibiotics as the pretreatment procedure in comparison to those that did not use any antibiotics before FMT (54.0% vs. 25.1%, P=0.03). Limitations to this analysis include significant heterogeneity related to the administration route, the use of fresh or frozen stool, and number of treatments.
In conclusion, it appears that administration of antibiotic pretreatment before FMT may increase the rate of clinical remission in adult UC patients. To understand the underlying mechanisms by which antibiotic pretreatment can enhance the therapeutic efficacy of FMT and to determine the most appropriate antibiotic regimen, further well-designed randomized controlled trials are required. In addition, in that antibiotic therapy can induce remission in patients with active UC6 independent of possible effects in enhancing the effectiveness of FMT, the design of future studies should consider including a study arm with antibiotics alone.
Pigneur, B. & Sokol, H. Fecal microbiota transplantation in inflammatory bowel disease: the quest for the holy grail. Mucosal Immunol. 9, 1360–1365 (2016).
Ishikawa, D., Osada, T., Haga, K., Kodani, T., Shibuya, T. & Watanabe, S. Combination therapy of fresh faecal microbial transplantation and antibiotics for ulcerative colitis. J. Crohn’s Colitis 10 (Suppl 1), S335–S336 (2016).
Colman, R.J. & Rubin, D.T. Fecal microbiota transplantation as therapy for inflammatory bowel disease: a systematic review and meta-analysis. J. Crohn’s Colitis 8, 1569–1581 (2014).
Moayyedi, P. et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149, 102–109.e6 (2015).
Rossen, N.G. et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterology 149, 110–118.e4 (2015).
Khan, K.J. et al. Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am. J. Gastroenterol. 106, 661–673 (2011).
The authors declared no conflict of interest.
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Keshteli, A., Millan, B. & Madsen, K. Pretreatment with antibiotics may enhance the efficacy of fecal microbiota transplantation in ulcerative colitis: a meta-analysis. Mucosal Immunol 10, 565–566 (2017). https://doi.org/10.1038/mi.2016.123
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