Intestinal Research

Original Articles

Inflammatory bowel diseases

5-Aminosalicylic acid intolerance is associated with a risk of adverse clinical outcomes and dysbiosis in patients with ulcerative colitis: Shinta Mizuno, Keiko Ono, Yohei Mikami, Makoto Naganuma, Tomohiro Fukuda, Kazuhiro Minami, Tatsuhiro Masaoka, Soichiro Terada, Takeshi Yoshida, Keiichiro Saigusa, Norimichi Hirahara, Hiroaki Miyata, Wataru Suda, Masahira Hattori, Takanori Kanai; Intest Res 2020;18(1):69-78. Published online January 30, 2020; DOI: https://doi.org/10.5217/ir.2019.00084

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Background/Aims
5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota.
Methods
We performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC.
Results
Of 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P< 0.001). In 108 patients undergoing treatment with anti-tumor necrosis factor biologics, 5-ASA intolerance increased the incidence of additional induction therapy after starting biologics (P< 0.001). The 5-ASA intolerance group had a greater abundance of bacteria in the genera Faecalibacterium, Streptococcus, and Clostridium than the 5-ASA tolerance group (P< 0.05).
Conclusions
In patients with UC, 5-ASA intolerance is associated with a risk of adverse clinical outcomes and dysbiosis. Bacterial therapeutic optimization of 5-ASA administration may be important for improving the prognosis of patients with UC.

Citations

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IBD

β-(1,3)-Glucan derived from Candida albicans induces inflammatory cytokines from macrophages and lamina propria mononuclear cells derived from patients with Crohn's disease: Kiyoto Mori, Makoto Naganuma, Shinta Mizuno, Hiroaki Suzuki, Mina T. Kitazume, Katsuyoshi Shimamura, Sayako Chiba, Akira Sugita, Katsuyoshi Matsuoka, Tadakazu Hisamatsu, Takanori Kanai; Intest Res 2018;16(3):384-392. Published online July 27, 2018; DOI: https://doi.org/10.5217/ir.2018.16.3.384

Abstract PDF Supplementary Material PubReader ePub

Background/Aims

Recent research has highlighted the importance of interactions between commensal fungi and intestinal inflammation. However, there are few studies investigating whether commensal fungi contribute to inflammation in patients with Crohn's disease (CD). The aim of this study is to investigate reveal interactions between commensal fungi and host immune cells in CD.

Methods

CD14-positive monocytes were isolated from peripheral blood mononuclear cells from healthy human volunteers and then differentiated in the presence of macrophage colony-stimulating factor (M-CSF) (referred to as M-macrophages, M-Mϕs) or M-CSF and interferon-γ (IFN-γ) (referred to as M-gamma macrophages, Mγ-Mϕs). Cytokine production by these in vitro differentiated macrophages in response to β-(1,3)-glucan was analyzed by flow cytometry. Expression of Dectin-1 was examined using flow cytometry, western blotting, and quantitative reverse transcription-polymerase chain reaction. Cytokine production by in vitro differentiated macrophages in response to β-(1,3)-glucan was measured in the presence of an anti-Dectin-1 receptor antagonist, anti-Syr, or an anti-Fas-1 antibody. Cytokine production by lamina propria mononuclear cells (LPMCs) derived from CD patients in response to β-(1,3)-glucan was also analyzed.

Results

Mγ-Mϕs produced a large amount of tumor necrosis factor-α (TNF-α) and interleukin-6 in response to β-(1,3)-glucan. Dectin-1 expression was significantly higher in Mγ-Mϕs than in M-Mϕs. The increase in TNF-α production by Mγ-Mϕs stimulated with glucan was reversed by blocking Dectin-1, Syr or Fas-1. LPMCs derived from CD patients stimulated with β-(1,3)-glucan produced significantly higher amount of TNF-α than LPMCs derived from UC patients.

Conclusions

These results suggest that commensal fungal microbiota may contribute to the pathogenesis of CD by inducing macrophages-derived pro-inflammatory cytokines.

Citations

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Case Report

IBD

Fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient with ulcerative colitis: Kosaku Nanki, Shinta Mizuno, Katsuyoshi Matsuoka, Keiko Ono, Shinya Sugimoto, Hiroki Kiyohara, Mari Arai, Moeko Nakashima, Kozue Takeshita, Keiichiro Saigusa, Mitsutoshi Senoh, Tadashi Fukuda, Makoto Naganuma, Haru Kato, Wataru Suda, Masahira Hattori, Takanori Kanai; Intest Res 2018;16(1):142-146. Published online January 18, 2018; DOI: https://doi.org/10.5217/ir.2018.16.1.142

Abstract PDF PubReader ePub

Fecal microbiota transplantation (FMT) has been reported as a safe and effective therapy in patients with refractory and recurrent Clostridium difficile infection (CDI). FMT has also been reported as a promising therapy in patients with ulcerative colitis (UC). Both, CDI and UC, are believed to be caused by dysbiosis, such as altered compositions or decreased diversity of the intestinal microbiota. This report describes a patient with UC in remission with a second recurrent episode of CDI, who was treated with FMT. A single FMT performed via colonoscopy completely resolved the patient's diarrhea and eradicated C. difficile bacteriologically without any severe complications. Molecular biological analysis of the patient's fecal microbiota showed that FMT could dramatically change the altered composition of intestinal microbiota and restore its diversity. Despite the restoration of the intestinal microbiota, FMT could not prevent a relapse of UC in this patient. However, it improved the intestinal symptoms of CDI and could prevent further recurrences of CDI.

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Original Article

Single fecal microbiota transplantation failed to change intestinal microbiota and had limited effectiveness against ulcerative colitis in Japanese patients: Shinta Mizuno, Kosaku Nanki, Katsuyoshi Matsuoka, Keiichiro Saigusa, Keiko Ono, Mari Arai, Shinya Sugimoto, Hiroki Kiyohara, Moeko Nakashima, Kozue Takeshita, Makoto Naganuma, Wataru Suda, Masahira Hattori, Takanori Kanai; Intest Res 2017;15(1):68-74. Published online January 31, 2017; DOI: https://doi.org/10.5217/ir.2017.15.1.68

Abstract PDF Supplementary Material PubReader ePub

Background/Aims

Recent developments in analytical techniques including next-generation sequencing have clarified the correlation between intestinal microbiota and inflammatory bowel disease. Fecal microbiota transplantation (FMT) for patients with ulcerative colitis (UC) is proposed as a potential approach to resolving their dysbiosis; however, its safety and efficacy have not been confirmed. This single-arm, open-label, non-randomized study aimed to evaluate the safety and efficacy of FMT for Japanese patients with UC as the first registered clinical trial in Japan.

Methods

We enrolled 10 patients with active UC despite medical therapy. The donors were the patients' relatives and were carefully screened for infectious diseases. Fecal material was administered via colonoscopy, and the primary endpoint was the presence or absence of serious adverse events related to FMT. The secondary endpoint was a change in partial Mayo score at 12 weeks post-FMT. Scores ≤2 were considered a clinical response. Fecal samples were collected to follow changes in gut microbiota, while extracted complementary DNA were analyzed by a next-generation sequencer. We obtained written informed consent from all patients and donors. This study was approved by our Institutional Review Board and is registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN 000012814).

Results

Five patients with moderate disease and five with severe disease were enrolled. No severe adverse effects were observed. One patient achieved clinical response; however, none of the patients' microbiota diversity recovered to the donor levels.

Conclusions

The use of single FMT for UC was safe; however, we failed to show its clinical efficacy and potential to change the intestinal microbiota.

Citations

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