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The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis

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Abstract

Purpose

Ulcerative colitis (UC) is a chronic, relapsing, and refractory disorder of the intestine. Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the preferred and standard surgical procedure for patients’ refractory to medical therapy. Pouchitis is one of the most common long-term complications after IPAA. In the present study, the safety and efficacy of Clostridium butyricum MIYAIRI (CBM) as a probiotic were examined.

Methods

A randomized and placebo-controlled study was performed. Seventeen patients were recruited from 2007 to 2013. Nine tablets of MIYA-BM® or placebo were orally administered once daily. The cumulative pouchitis-free survival, pouch condition (using the modified pouch disease activity index), and blood parameters were evaluated. A fecal sample analysis was also performed.

Results

Subjects were randomly allocated to receive MIYA-BM or placebo (9 and 8 subjects, respectively). One subject in the MIYA-BM group and four subjects in the placebo group developed pouchitis. No side effects occurred in either group. Characteristic intestinal flora was observed in each group.

Conclusions

Our results suggest that probiotic therapy with CBM achieved favorable results with minimal side effects and might be a useful complementary therapy for the prevention of pouchitis in patients with UC who have undergone IPAA.

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Abbreviations

Alb:

Albumin

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

BUN:

Blood urea nitrogen

CBM:

Clostridium butyricum MIYAIRI

CD:

Crohn’s disease

Cre:

Creatinine

CRP:

C-reactive protein

CTCAE v.4.0:

Common terminology criteria for adverse events version 4.0

DNA:

Deoxyribonucleic acid

E. coli :

Escherichia coli

EDTA:

Ethylenediaminetetraacetic acid

FAP:

Familial adenomatous polyposis syndrome

Hb:

Hemoglobin

IBD:

Inflammatory bowel disease

IPAA:

Abdominal colectomy with ileal pouch anal anastomosis

ITT:

Intention to treat

IF-γ:

Interferon γ

IL-10:

Interleukin 10

mPDAI:

Modified pouchitis disease activity index

NF-κB:

Nuclear factor kappa B

OTUs:

Operational taxonomic units

PCR:

Polymerase chain reaction

PDAI:

Pouchitis disease activity index

RBP:

Retinol-binding proteins

rRNA:

Ribosomal ribonucleic acid

ROS:

Reactive oxygen species

SDS:

Sodium dodecyl sulfate

TTR:

Transthyretin

TLR4:

Toll-like receptor 4

TNF-α:

Tumor necrosis factor α

TP:

Total protein

T-RFLP:

Terminal restriction fragment polymorphism

UC:

Ulcerative colitis

WBC:

White blood cell

6-FAM:

6′-Carboxyfluorescein

% AUC:

% Area under the curve

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Acknowledgments

All authors read and approved the final manuscript. The authors are grateful to M. Takahashi (Miyarisan Pharmaceutical Co., Ltd.), K. Oka (Miyarisan Pharmaceutical Co., Ltd.), A. Ishikawa (Miyarisan Pharmaceutical Co., Ltd.), S. Shinzaki (Osaka University), N. Hayashi (Osaka University), and H. Urushima (Osaka University) for helpful comments and provision of information.

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Authors and Affiliations

  1. Department of Integrative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Asuka Yasueda & Toshinori Ito

  2. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Tsunekazu Mizushima, Junichi Nishimura, Hideki Osawa & Masaki Mori

  3. Department of Therapeutics for Inflammatory Bowel Diseases, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Tsunekazu Mizushima

  4. Department of Surgery, Nishinomiya Municipal Central Hospital, 8-24 Hayashidacho, Nishinomiya, Hyogo, 663-8014, Japan

    Riichiro Nezu

  5. Division of Nutrition and Medical Engineering, Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Ryoko Sumi

  6. Miyarisan Pharmaceutical Co. Ltd., 102-15 Sakaki, Hanishina, Nagano, 389-0682, Japan

    Mamoru Tanaka

  7. Gastroenterological Surgery, Hanwasumiyoshi General Hospital, 3-2-9 Minami Sumiyoshi, Sumiyoshi-ku, Osaka, 558-0041, Japan

    Yasuyuki Kai

  8. Gastroenterological Surgery, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Kita-ku, Sakai, Osaka, 591-8025, Japan

    Masaki Hirota

  9. Division of Collaborative Research for Next Generation Endoscopic Intervention, Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Kiyokazu Nakajima

Authors
  1. Asuka Yasueda
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  2. Tsunekazu Mizushima
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  3. Riichiro Nezu
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  4. Ryoko Sumi
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  5. Mamoru Tanaka
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  6. Junichi Nishimura
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  7. Yasuyuki Kai
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  8. Masaki Hirota
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  9. Hideki Osawa
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  10. Kiyokazu Nakajima
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  11. Masaki Mori
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  12. Toshinori Ito
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Corresponding author

Correspondence to Toshinori Ito.

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Conflict of interest

This work was mainly carried out by funds from the investigators themselves and was partly supported by Miyarisan Pharmaceutical Co., Ltd. They provided the placebo and the meeting space and analyzed fecal microbiota. Other costs related to this research were covered by the Department of Integrative Medicine, Osaka University Graduate School of Medicine. This laboratory is supported by donated funds and is managed by a fund from Amino Up Chemical Co., Ltd. Mamoru Tanaka is an employee of Miyarisan Pharmaceutical Co. Ltd. and supervised the measurement of the fecal bacterial flora. For the remaining authors, no conflicts were declared. However, none of the sponsors had any control over the research, writing, or publication of this work.

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Yasueda, A., Mizushima, T., Nezu, R. et al. The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis. Surg Today 46, 939–949 (2016). https://doi.org/10.1007/s00595-015-1261-9

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