Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan

Motonobu Hamazaki, Tsunaki Sawada, Takeshi Yamamura, Keiko Maeda, Yasuyuki Mizutani, Eri Ishikawa, Satoshi Furune, Kenta Yamamoto, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Masanao Nakamura, Mitsuhiro Fujishiro, Motonobu Hamazaki, Tsunaki Sawada, Takeshi Yamamura, Keiko Maeda, Yasuyuki Mizutani, Eri Ishikawa, Satoshi Furune, Kenta Yamamoto, Takuya Ishikawa, Naomi Kakushima, Kazuhiro Furukawa, Eizaburo Ohno, Takashi Honda, Hiroki Kawashima, Masatoshi Ishigami, Masanao Nakamura, Mitsuhiro Fujishiro

Abstract

Background: Fecal microbiota transplantation (FMT) is a potential treatment for irritable bowel syndrome (IBS), but its efficacy in Japanese IBS patients is unknown. This study aimed to evaluate the efficacy, side effects, and microbiome changes following FMT in Japanese IBS patients.

Methods: Seventeen Japanese patients with refractory IBS received FMT (4 donors) under colonoscopy. Responders were defined by an improvement in the IBS severity index (IBS-SI) of 50 points or more after 12 weeks. We evaluated the IBS-SI and Bristol Stool Form Scale (BSFS) and compared the diversity and microbiome before and 12 weeks after FMT. For the microbiome, we analyzed the V3-V4 region of the 16S rRNA gene.

Results: IBS-SI decreased an average of 115.58 points after 12 weeks, and 10 patients (58.8%) were considered responders. Eight patients with diarrhea (66.7%) and three patients with constipation (60.0%) showed improvement in the BSFS. Two patients complained of mild abdominal pain, but there were no cases with severe side-effects. α-diversity was increased only in the responder group (p = 0.017). Patients who closely paralleled the donor microbiome had a higher rate of IBS-SI improvement. The relative abundance of Neisseria and Akkermansia increased and Desulfovibrio and Delftia were decreased in the responder group after FMT.

Conclusions: Following FMT, about 60% of Japanese patients with IBS showed improvement in both the IBS-SI and BSFS, without severe side effects. Increased α-diversity and similarity to the donor microbiome after FMT may be associated with better treatment effects.

Trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN000026363). Registered 31 May 2017, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000026363 . The study was registered prospectively.

Keywords: Fecal microbiota transplantation; Gastrointestinal endoscopy; Irritable bowel syndrome; Microbiome.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Principal coordinate analysis plot in donor and irritable bowel syndrome patients after fecal microbiota transplantation. a Principal Coordinate Analysis (PCoA) plot of patients (N = 17) with irritable bowel syndrome (IBS) and donors (N = 4). a, b Changes in patients’ microbiome were evaluated based on the distance traveled on the PCoA plot, as defined below. c Change of IBS severity index (IBS-SI) in patients classified as belonging to the Near Donnor Group (NCG, N = 13) and the Far Donor Group (FDG, N = 4) before and at 12 weeks after fecal microbiota transplantation (FMT)
Fig. 2
Fig. 2
Irritable bowel syndrome severity index. a Overall score. b Subscale scores for five items of irritable bowel syndrome severity index (IBS-SI) in patients treated with fecal microbiota transplantation (FMT)
Fig. 3
Fig. 3
Bristol stool form scale. a Change in stool form scale in responder (red line) and non-responder (blue line) patients with diarrhea-predominant irritable bowel syndrome (IBS-D, N = 12) and b constipation-predominant irritable bowel syndrome (IBS-C, N = 5) using the Bristol stool form scale before and 4, 8, and 12 weeks after fecal microbiota transplantation (FMT)
Fig. 4
Fig. 4
Alpha-diversity of gut microbiome in patients with irritable bowel syndrome after fecal microbiota transplantation. a Left: Diversity (Chao1) of microbiome in 17 patients with irritable bowel syndrome (IBS) before and at 4 and 12 weeks after fecal microbiota transplantation (FMT). b Right: Diversity (Chao1) of microbiome in 10 patients in responders (N = 10) and non-responders (N = 7) before and at 12 weeks after fecal microbiota transplantation (FMT)
Fig. 5
Fig. 5
Differences in microbiome before and at 12 weeks after fecal microbiota transplantation. Significant differences were found in the microbiome before fecal microbiota transplantation (FMT) and at 12 weeks by linear discriminant analysis effect size (LEfSe) in the responder (N = 10) and non-responder (N = 7) groups. a In the responder group, two genera, Neissria and Akkermansia, were significantly increased, and two genera, Desulfovibrio and Delftia, were significantly decreased. b In the non-responder group, two genera, Atopobium and Bilophila, increased and one genera, Veillonella, decreased

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