Intestinal Research

Original Articles

IBD

Ulcerative colitis-associated neoplasms often harbor poor prognostic histologic components with low detection by biopsy: Ryoya Sakakibara, Shinya Sugimoto, Kaoru Takabayashi, Hiroki Kiyohara, Yusuke Wakisaka, Yuta Kaieda, Miho Kawaida, Yusuke Yoshimatsu, Tomohisa Sujino, Naoki Hosoe, Motohiko Kato, Masayuki Shimoda, Yohei Mikami, Yasushi Iwao, Takanori Kanai; Intest Res 2024;22(4):428-438. Published online May 7, 2024; DOI: https://doi.org/10.5217/ir.2024.00006

Abstract PDF PubReader ePub: Background/Aims
Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features.
Methods
This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component.
Results
Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%).
Conclusions
This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.

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IBD

Risk of venous thromboembolism with a central venous catheter in hospitalized Japanese patients with inflammatory bowel disease: a propensity score-matched cohort study: Yasuhiro Aoki, Hiroki Kiyohara, Yohei Mikami, Kosaku Nanki, Takaaki Kawaguchi, Yusuke Yoshimatsu, Shinya Sugimoto, Tomohisa Sujino, Kaoru Takabayashi, Naoki Hosoe, Haruhiko Ogata, Yasushi Iwao, Takanori Kanai; Intest Res 2023;21(3):318-327. Published online February 10, 2023; DOI: https://doi.org/10.5217/ir.2022.00116

Abstract PDF Supplementary Material PubReader ePub

Background/Aims
Thromboprophylaxis is recommended for hospitalized patients with inflammatory bowel disease (IBD) in Western countries, although it is selectively administered to high-risk patients in East Asia. A central venous catheter (CVC) is commonly placed in patients with IBD. Although CVC placement is considered a risk factor for venous thromboembolism (VTE), the degree of increased risk in patients with IBD is uncertain. This study aimed to identify the risk of VTE with CVC placement in hospitalized Japanese patients with IBD without thromboprophylaxis.
Methods
This retrospective cohort study included patients with ulcerative colitis or Crohn’s disease who were admitted for disease flares at Keio University Hospital between January 2016 and December 2020. Patients who already had thrombosis or were administered any antithrombotic treatment on admission were excluded. VTE development during the hospitalization was surveyed, and VTE risk associated with CVC indwelling was estimated using propensity score matching and inverse probability of treatment weighting analyses.
Results
Altogether, 497 hospitalized patients with IBD (ulcerative colitis, 327; Crohn’s disease, 170) were enrolled. VTE developed in 9.30% (12/129) of catheterized patients and in 0.82% (3/368) of non-catheterized patients. The propensity score matching yielded 127 matched pairs of patients. The catheterized group demonstrated higher odds for VTE than the non-catheterized group (odds ratio, 13.15; 95% confidence interval, 1.68–102.70). A similar result was obtained in the inverse probability of treatment weighting analysis (odds ratio, 11.02; 95% confidence interval, 2.64–46.10).
Conclusions
CVC placement is a major risk factor for VTE among hospitalized Japanese patients with IBD without thromboprophylaxis.

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Incidence of Venous Thromboembolism in Asian Patients With Inflammatory Bowel Disease: A Systematic Review and Meta‐Analysis
Joo Hye Song, Sung Ryul Shim, Dae Sung Kim, Hoon Sup Koo, Kyu Chan Huh
Journal of Gastroenterology and Hepatology.2025; 40(4): 774. CrossRef
Safety and effectiveness of tofacitinib in Korean adult patients with ulcerative colitis: post-marketing surveillance study
Hyuk Yoon, Byong Duk Ye, Sang-Bum Kang, Kang-Moon Lee, Chang Hwan Choi, Joo-young Jo, Juwon Woo, Jae Hee Cheon
BMC Gastroenterology.2024;[Epub] CrossRef

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Perspective

Endoscopy

Reviewing not Homer’s Iliad, but “Kai Bao Ben Cao”: indigo dye—the past, present, and future: Yusuke Yoshimatsu, Tomohisa Sujino, Takanori Kanai; Intest Res 2023;21(2):174-176. Published online June 14, 2022; DOI: https://doi.org/10.5217/ir.2022.00018

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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

Abstract PDF Supplementary Material PubReader ePub

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.

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Drug-induced Interstitial Nephritis in a Patient with Ulcerative Colitis Treated with 5-Aminosalicylic Acid
Daichi Hayashi, Tsutomu Nishida, Naoto Osugi, Yasuo Kusunoki, Satoru Okabe, Yoshifumi Fujii, Dai Nakamatsu, Kengo Matsumoto, Masashi Yamamoto, Koji Fukui
Internal Medicine.2024; 63(8): 1081. CrossRef
The impact of 5-aminosalicylates on the efficacy of mesenchymal stem cell therapy in a murine model of ulcerative colitis
Huanhuan Chen, Huimin Wang, XiaoJing Xu, Ya'nan Hu, Jing Su, Dongdong Li, Zimu Li, Shixiang Feng, Jinming Liu, Huanxiang Zhang, Xiaoyan Wang
International Immunopharmacology.2024; 134: 112255. CrossRef
Characteristics of Mucosa-Associated Microbiota in Ulcerative Colitis Patients with 5-Aminosalicylic Acid Intolerance
Hiroshi Matsumoto, Momoyo Sasahira, Tei Tei Go, Shogen Yo, Takehiro Ninomiya, Motoyasu Osawa, Osamu Handa, Eiji Umegami, Ryo Inoue, Akiko Shiotani
Biomedicines.2024; 12(9): 2125. CrossRef
Lithium Coupled with C6-Carboxyl Improves the Efficacy of Oligoguluronate in DSS-Induced Ulcerative Colitis in C57BL/6J Mice
Jiayi Li, Meng Shao, Hao Liu, Peng Guo, Fei Liu, Mingfeng Ma, Quancai Li
Marine Drugs.2024; 22(12): 573. CrossRef
Persistence of newly prescribed 5-aminosalicylic acid in patients with ulcerative colitis: A nationwide comprehensive database study
Tatsuya Noda, Kotaro Kuwaki, Munehito Machida, Yasuyuki Okumura, Yuichi Nishioka, Tomoya Myojin, Tomoaki Imamura, Barry Kweh
PLOS ONE.2024; 19(12): e0316181. CrossRef
Manipulating Microbiota in Inflammatory Bowel Disease Treatment: Clinical and Natural Product Interventions Explored
Mengjie Zhu, Yijie Song, Yu Xu, Hongxi Xu
International Journal of Molecular Sciences.2023; 24(13): 11004. CrossRef
Risk factors for intolerance of oral 5‐aminosalicylic acid preparations in pediatric ulcerative colitis
Naoki Abe, Naomi Iwata, Ryuhei Yasuoka, Daisuke Nishida, Asami Oohara, Haruna Nakaseko, Shiro Sugiura, Shinji Kawabe
Pediatrics International.2023;[Epub] CrossRef
CURRENT STATUS, PROBLEMS AND PROSPECTS OF ULCERATIVE COLITIS MEDICAL CORRECTION (LITERATURE REVIEW)
T. O. Briukhanova, O. A. Nakonechna, O. V Babenko
Bulletin of Problems Biology and Medicine.2023; 1(3): 28. CrossRef
Significance of 5-Aminosalicylic Acid Intolerance in the Clinical Management of Ulcerative Colitis
Yohei Mikami, Junya Tsunoda, Shohei Suzuki, Ichiro Mizushima, Hiroki Kiyohara, Takanori Kanai
Digestion.2023; 104(1): 58. CrossRef
Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease
Kaoru Suzuki, Yoichi Kakuta, Takeo Naito, Tetsuya Takagawa, Hiroyuki Hanai, Hiroshi Araki, Yu Sasaki, Hirotake Sakuraba, Makoto Sasaki, Tadakazu Hisamatsu, Satoshi Motoya, Takayuki Matsumoto, Motoyuki Onodera, Yoh Ishiguro, Hiroshi Nakase, Akira Andoh, Sa
Inflammatory Bowel Diseases.2022; 28(1): 21. CrossRef
Classification and clinical features of adverse drug reactions in patients with ulcerative colitis treated with 5‐aminosalicylate acid: a single-center, observational study
Yuri Tsujii, Tsutomu Nishida, Naoto Osugi, Yoshifumi Fujii, Aya Sugimoto, Dai Nakamatsu, Kaori Mukai, Kengo Matsumoto, Shiro Hayashi, Masashi Yamamoto, Sachiko Nakajima
Scandinavian Journal of Gastroenterology.2022; 57(2): 190. CrossRef
The Prognostic Value of Residual Nonrectal Inflammation in Ulcerative Colitis
Eun Ae Kang
Gut and Liver.2022; 16(3): 487. CrossRef
Personalized medicine in inflammatory bowel disease: Perspectives on Asia
Su Hyun Park, Sang Hyoung Park
Journal of Gastroenterology and Hepatology.2022; 37(8): 1434. CrossRef
Updates on conventional therapies for inflammatory bowel diseases: 5-aminosalicylates, corticosteroids, immunomodulators, and anti-TNF-α
Jihye Park, Jae Hee Cheon
The Korean Journal of Internal Medicine.2022; 37(5): 895. CrossRef
The emerging microbiome‐based approaches to IBD therapy: From SCFAs to urolithin A
Mohammad Rudiansyah, Saade Abdalkareem Jasim, Bakhadir S. Azizov, Vadim Samusenkov, Walid Kamal Abdelbasset, Ghulam Yasin, Hawraa Jabbar Mohammad, Mohammed Abed Jawad, Trias Mahmudiono, Seyed Reza Hosseini‐Fard, Rasoul Mirzaei, Sajad Karampoor
Journal of Digestive Diseases.2022; 23(8-9): 412. CrossRef
Multicenter survey on mesalamine intolerance in patients with ulcerative colitis
Sakiko Hiraoka, Akiko Fujiwara, Tatsuya Toyokawa, Reiji Higashi, Yuki Moritou, Shinjiro Takagi, Kazuhiro Matsueda, Seiyuu Suzuki, Jiro Miyaike, Toshihiro Inokuchi, Masahiro Takahara, Jun Kato, Hiroyuki Okada
Journal of Gastroenterology and Hepatology.2021; 36(1): 137. CrossRef
Enteric-coated gelatin nanoparticles mediated oral delivery of 5-aminosalicylic acid alleviates severity of DSS-induced ulcerative colitis
Anas Ahmad, Md. Meraj Ansari, Rakesh Kumar Mishra, Ajay Kumar, Akshay Vyawahare, Rahul Kumar Verma, Syed Shadab Raza, Rehan Khan
Materials Science and Engineering: C.2021; 119: 111582. CrossRef
Bacteriotherapy for inflammatory bowel disease
Yusuke Yoshimatsu, Yohei Mikami, Takanori Kanai
Inflammation and Regeneration.2021;[Epub] CrossRef
Treatment of inflammatory bowel diseases: focusing on 5-aminosalicylates and immunomodulators
You Sun Kim
Journal of the Korean Medical Association.2021; 64(9): 596. CrossRef
The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies
Yu Hu, Zhen Ye, Mingquan Wu, Yingqi She, Linzhen Li, Yujie Xu, Kaihua Qin, Zhipeng Hu, Maoyi Yang, Fating Lu, Qiaobo Ye
Frontiers in Medicine.2021;[Epub] CrossRef
Pharmacogenetics-based personalized treatment in patients with inflammatory bowel disease: A review
Ji Young Chang, Jae Hee Cheon
Precision and Future Medicine.2021; 5(4): 151. CrossRef
5‐aminosalicylate–intolerant patients are at increased risk of colectomy for ulcerative colitis
Shuji Hibiya, Yusuke Matsuyama, Toshimitsu Fujii, Chiaki Maeyashiki, Eiko Saito, Kimiko Ito, Hiromichi Shimizu, Ami Kawamoto, Maiko Motobayashi, Kento Takenaka, Masakazu Nagahori, Masayuki Kurosaki, Tsunehito Yauchi, Kazuo Ohtsuka, Takeo Fujiwara, Ryuichi
Alimentary Pharmacology & Therapeutics.2021; 53(1): 103. CrossRef
Mesalazine allergy and an attempt at desensitization therapy in patients with inflammatory bowel disease
Satohiro Matsumoto, Hirosato Mashima
Scientific Reports.2020;[Epub] CrossRef

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Inflammatory bowel diseases

Anti-MAdCAM-1 antibody (PF-00547659) for active refractory Crohn’s disease in Japanese and Korean patients: the OPERA study: Masayuki Saruta, Dong Il Park, Young-Ho Kim, Suk-Kyun Yang, Byung-Ik Jang, Jae Hee Cheon, Jong Pil Im, Takanori Kanai, Tatsuro Katsuno, Yoh Ishiguro, Makoto Nagaoka, Naoki Isogawa, Yinhua Li, Anindita Banerjee, Alaa Ahmad, Mina Hassan-Zahraee, Robert Clare, Kenneth J. Gorelick, Fabio Cataldi, Mamoru Watanabe, Toshifumi Hibi; Intest Res 2020;18(1):45-55. Published online January 30, 2020; DOI: https://doi.org/10.5217/ir.2019.00039

Abstract PDF PubReader ePub

Background/Aims
PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn’s disease (CD).
Methods
OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein > 3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn’s Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients.
Results
In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment.
Conclusions
In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results. (Trial Registration Number: NCT01276509)

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Development of New Molecularly Targeted Agents in Inflammatory Bowel Disease
Hiroshi Nakase
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Jae-Young Lee, Hyun Woo Ma, Ji Hyung Kim, I Seul Park, Mijeong Son, Keun Ho Ryu, Jieun Shin, Seung Won Kim, Jae Hee Cheon
Gut and Liver.2023; 17(5): 766. CrossRef
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Maximilian Wiendl, Emily Becker, Tanja M. Müller, Caroline J. Voskens, Markus F. Neurath, Sebastian Zundler
Frontiers in Immunology.2021;[Epub] CrossRef
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Hanne Salmenkari, Riitta Korpela, Heikki Vapaatalo
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Virginia Solitano, Tommaso Lorenzo Parigi, Elisa Ragaini, Silvio Danese
Expert Opinion on Investigational Drugs.2021; 30(10): 1037. CrossRef
Emerging therapeutic options in inflammatory bowel disease
Jesus K Yamamoto-Furusho, Norma N Parra-Holguín
World Journal of Gastroenterology.2021; 27(48): 8242. CrossRef

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Review

IBD

Current new challenges in the management of ulcerative colitis: Tomohiro Fukuda, Makoto Naganuma, Takanori Kanai; Intest Res 2019;17(1):36-44. Published online January 25, 2019; DOI: https://doi.org/10.5217/ir.2018.00126

Abstract PDF PubReader ePub

Ulcerative colitis (UC) is a chronic inflammatory condition of the gastrointestinal tract. Although the cause of UC is postulated to be multifactorial in nature, including genetic predisposition, epithelial barrier defects, dysregulation of immune responses, and environmental factors, the specific pathogenesis of UC is still incompletely understood. In the treatment of UC so far, a method of suppressing immunity and treating it has been mainstream. Immunosuppressant drugs, including thiopurines (azathioprine or 6-mercaptopurine), anti-tumor necrosis factor-α (anti-TNF-α) antibody (infliximab and adalimumab), and calcineurin inhibitor, can be used in treat patients with corticosteroid-dependent and/or corticosteroid-refractory moderateto- severe UC. Recently, in addition to such a conventional therapeutic agent, golimumab, which is the first transgenic human monoclonal anti-TNF-α antibody to be fabricated, anti α-4/β-7 integrin antibody, and Janus kinase inhibitor have been reported to novel immunosuppressant therapy. Furthermore, other treatments with unique mechanisms different from immunosuppression, have also been suggested, including fecal microbiota transplantation and Indigo naturalis, which is a Chinese herbal medicine. We compared the features and efficacy of these new treatments. In this issue, the features and treatment options for these new treatments is reviewed.

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Does cytomegalovirus load predict the outcome of acute severe ulcerative colitis?
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Case Report

IBD

5-Aminosalicylic acid aggravates colitis mimicking exacerbation of ulcerative colitis: Jun Miyoshi, Katsuyoshi Matsuoka, Atsushi Yoshida, Makoto Naganuma, Tadakazu Hisamatsu, Tomoharu Yajima, Nagamu Inoue, Susumu Okamoto, Yasushi Iwao, Haruhiko Ogata, Fumiaki Ueno, Toshifumi Hibi, Takanori Kanai; Intest Res 2018;16(4):635-640. Published online October 10, 2018; DOI: https://doi.org/10.5217/ir.2018.00015

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Ulcerative colitis (UC) is one of the major clinical phenotypes of inflammatory bowel diseases. Although 5-aminosalicylic acid (5-ASA) is widely used for UC and its efficacy and safety have been demonstrated, a few patients paradoxically develop a severe exacerbation of colitis by 5-ASA administration. It is crucial to know clinical features including endoscopic findings in this condition for making a correct diagnosis and a prompt decision to withdraw the medication. Here, we report case series with UC exacerbated by 5-ASA. Medical records of 8 UC patients experiencing an exacerbation of colitis after induction of 5-ASA that was improved by the withdrawal of 5-ASA but also re-aggravated by dose increase or re-administration of 5-ASA were reviewed. The patients were newly diagnosed with UC, started 5-ASA and developed an exacerbation in approximately 2 to 3 weeks. They did not appear to have systemic allergic reactions. Seven of the 8 patients had a high fever. Three of 5 patients who undertook total colonoscopy showed right-side-dominant colitis. These findings suggest clinical characteristics in this condition. Further assessment of clinical and endoscopic features in more cases is necessary for establishing diagnostic criteria and understanding underlying mechanisms in those cases where 5-ASA aggravates the colitis.

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Brief Communication

IBD

Effect of elemental diet combined with infliximab dose escalation in patients with Crohn's disease with loss of response to infliximab: CERISIER trial: Tadakazu Hisamatsu, Reiko Kunisaki, Shiro Nakamura, Tomoyuki Tsujikawa, Fumihito Hirai, Hiroshi Nakase, Kenji Watanabe, Kaoru Yokoyama, Masakazu Nagahori, Takanori Kanai, Makoto Naganuma, Hirofumi Michimae, Akira Andoh, Akihiro Yamada, Tadashi Yokoyama, Noriko Kamata, Shinji Tanaka, Yasuo Suzuki, Toshifumi Hibi, Mamoru Watanabe; Intest Res 2018;16(3):494-498. Published online July 27, 2018; DOI: https://doi.org/10.5217/ir.2018.16.3.494

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Therapeutic Advances in Gastroenterology.2025;[Epub] CrossRef
Nutrition and dietary therapy in paediatric inflammatory bowel disease
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Pancreatic Enzyme Replacement Therapy Improves Exclusive Enteral Nutrition Related Diarrhea in Crohn's Disease: A Prospective Randomized Trial
Jian Kang, Jing Wang, Juan Su, Wei Wang, Yueyue Lu, Zhishun Tang, Liping Zou, Anning Yin, Jiao Li, Haixia Ren, Qian Zhou, Huipeng Wan, Ping An
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Prospective study of an adalimumab combined with partial enteral nutrition in the induction period of Crohn’s disease
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Emma P Halmos, Lihi Godny, Julie Vanderstappen, Chen Sarbagili-Shabat, Vaios Svolos
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Lara Hart, Charlotte M. Verburgt, Eytan Wine, Mary Zachos, Alisha Poppen, Mallory Chavannes, Johan Van Limbergen, Nikhil Pai
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Original Article

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

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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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Heat Shock Protein SSA1 Enriched in Hypoxic Secretome of Candida albicans Exerts an Immunomodulatory Effect via Regulating Macrophage Function
Wei Teng, Phawinee Subsomwong, Kouji Narita, Akio Nakane, Krisana Asano
Cells.2024; 13(2): 127. CrossRef
Antifungal immunity mediated by C-type lectin receptors may be a novel target in immunotherapy for urothelial bladder cancer
Tianhang Li, Tianyao Liu, Zihan Zhao, Yuchen Pan, Xinyan Xu, Yulin Zhang, Shoubin Zhan, Shengkai Zhou, Wenjie Zhu, Hongqian Guo, Rong Yang
Frontiers in Immunology.2022;[Epub] CrossRef
Serum 1,3-beta-D-glucan as a noninvasive test to predict histologic activity in patients with inflammatory bowel disease
Katia Farias e Silva, Hayandra F Nanini, Cynthia Machado Cascabulho, Siane L B Rosas, Patricia T Santana, Antonio José de V Carneiro, Elias Anaissie, Marcio Nucci, Heitor Siffert Pereira de Souza
World Journal of Gastroenterology.2021; 27(9): 866. CrossRef
Effects of Medicinal Fungi-Derived β-Glucan on Tumor Progression
Vaclav Vetvicka, Tamara V. Teplyakova, Alexandra B. Shintyapina, Tatiana A. Korolenko
Journal of Fungi.2021; 7(4): 250. CrossRef
The Role of IL-17-Producing Cells in Cutaneous Fungal Infections
Yu Sawada, Ayako Setoyama, Yumiko Sakuragi, Natsuko Saito-Sasaki, Haruna Yoshioka, Motonobu Nakamura
International Journal of Molecular Sciences.2021; 22(11): 5794. CrossRef

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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.

Citations

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Impact of Clostridioides difficile Infection on Clinical Outcomes in Hospitalized IBD Patients and the Role of Fecal Microbiota Transplantation: A Retrospective Cohort Study
Puo‐Hsien Le, Chyi‐Liang Chen, Chia‐Jung Kuo, Pai‐Jui Yeh, Chien‐Chang Chen, Yi‐Ching Chen, Cheng‐Tang Chiu, Hao‐Tsai Cheng, Yung‐Kuan Tsou, Yu‐Bin Pan, Cheng‐Hsun Chiu
The Kaohsiung Journal of Medical Sciences.2025;[Epub] CrossRef
Comparative Efficacy of Fecal Microbiota Transplantation in Treating Refractory or Recurrent Clostridioides difficile Infection among Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort Study
Jing-Han Chen, Cheng-Hsun Chiu, Chien-Chang Chen, Yi-Ching Chen, Pai-Jui Yeh, Chia-Jung Kuo, Cheng-Tang Chiu, Hao-Tsai Cheng, Yu-Bin Pan, Puo-Hsien Le
Biomedicines.2024; 12(7): 1396. CrossRef
Case report: Fecal microbiota transplant for Clostridium difficile infection in a pregnant patient with acute severe ulcerative colitis
Hanyu Wang, Feihong Deng, Min Luo, Xuehong Wang
Frontiers in Immunology.2024;[Epub] CrossRef
The first international Rome consensus conference on gut microbiota and faecal microbiota transplantation in inflammatory bowel disease
Loris Riccardo Lopetuso, Sara Deleu, Lihi Godny, Valentina Petito, Pierluigi Puca, Federica Facciotti, Harry Sokol, Gianluca Ianiro, Luca Masucci, Maria Abreu, Iris Dotan, Samuel Paul Costello, Ailsa Hart, Tariq H Iqbal, Sudarshan Paramsothy, Maurizio San
Gut.2023; 72(9): 1642. CrossRef
Fecal microbiota transplantation as therapy for recurrent Clostridioides difficile infection is associated with amelioration of delirium and accompanied by changes in fecal microbiota and the metabolome
Kazuyoshi Gotoh, Yoshihiko Sakaguchi, Haru Kato, Hayato Osaki, Yasutaka Jodai, Mitsutaka Wakuda, Akira Také, Shunji Hayashi, Eri Morita, Takehiko Sugie, Yoichiro Ito, Naoki Ohmiya
Anaerobe.2022; 73: 102502. CrossRef
Management of Clostridioides difficile infection in patients with inflammatory bowel disease
Sahil Khanna
Intestinal Research.2021; 19(3): 265. CrossRef
Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment
Xiao Yan Guo, Xin Juan Liu, Jian Yu Hao
Journal of Digestive Diseases.2020; 21(3): 147. CrossRef
RecurrentClostridium difficileInfection: Risk Factors, Treatment, and Prevention
Jung Hoon Song, You Sun Kim
Gut and Liver.2019; 13(1): 16. CrossRef
Current Status of Clostridium Difficile Infection
Akira Andoh, Shigeki Bamba
Nippon Daicho Komonbyo Gakkai Zasshi.2018; 71(10): 456. CrossRef

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Original Articles

Colonic dysmotility and morphological abnormality frequently detected in Japanese patients with irritable bowel syndrome: Takeshi Mizukami, Shinya Sugimoto, Tatsuhiro Masaoka, Hidekazu Suzuki, Takanori Kanai; Intest Res 2017;15(2):236-243. Published online April 27, 2017; DOI: https://doi.org/10.5217/ir.2017.15.2.236

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Background/Aims

Colonoscopy and computed tomography (CT) are used primarily to exclude organic diseases in patients with irritable bowel syndrome (IBS), rather than to assess the pathophysiology of IBS. We aimed to evaluate colonic dysmotility and morphology in Japanese patients with IBS.

Methods

One hundred eighty-four patients with IBS and 49 asymptomatic controls who underwent colonoscopy in combination with CT colonography or barium enema were retrospectively reviewed between 2008 and 2012. Water-aided colonoscopy was performed without sedation by a single endoscopist. The duration and pattern of colonic movement and cecal intubation time were recorded. To assess colonic morphology, barium enema or CT colonography were performed immediately after colonoscopy.

Results

Colonic dysmotility was more frequent in the IBS group (28.8% vs. 2.0% in controls, P<0.001), especially in cases of IBS with diarrhea (IBS-D) (IBS with constipation [IBS-C] 28.8% vs. IBS-D 60.0% vs. mixed IBS [IBS-M] 5.1%, P<0.001). Colonic morphological abnormality was more frequent in the IBS group than in the control group (77.7% vs. 24.5%, P<0.001), especially in IBS-M and IBS-C groups (IBS-C 77.5% vs. IBS-D 48.9% vs. IBS-M 100%, P<0.001). Most patients with IBS with colonic dysmotility had experienced stress related to their symptoms. Cecal intubation time was significantly longer in the IBS group than in the control group (12.1±6.9 minutes vs. 4.6±1.9 minutes, P<0.001).

Conclusions

Unsedated colonoscopy, combined with radiographic findings, can detect colonic dysmotility and morphological abnormality. Technical difficulties observed during cecal intubation may partially explain the pathophysiology of IBS.

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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

Citations to this article as recorded by

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Review

Immunological Abnormalities in the Pathogenesis of Inflammatory Bowel Disease: Tadakazu Hisamatsu, Yohei Mikami, Katsuyoshi Matsuoka, Takanori Kanai, Toshifumi Hibi; Intest Res 2012;10(4):317-323. Published online October 31, 2012; DOI: https://doi.org/10.5217/ir.2012.10.4.317

Abstract PDF

Crohn's disease and ulcerative colitis represent two distinct forms of inflammatory bowel diseases (IBD). In this paper, we discuss how immunological mechanisms contribute to the pathogenesis of IBD. Intestinal homeostasis is sustained by various kinds of cells, such as epithelial cells, lymphocytes, antigen presenting cells, and other innate immune cells. We pay special attention to intestinal CD14+ macrophages. Intestinal macrophages play a central role in the regulation of immune responses against commensal bacteria. In the physiological condition, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinfl ammatory cytokines. We identified a unique macrophage subset of IBD in the human intestine, which expressed both macrophage (CD14, CD33, CD68) and dendritic cell (DC) markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as interleukin (IL)-23 and tumor necrosis factor (TNF)-Ձ. In addition, the CD14+ macrophages contributed to interferon (IFN)-Ճ production rather than IL-17 production by lamina propria mononuclear cells dependent on IL-23. We discuss herein this IL-23/IFN-Ճ-positive feedback loop in IBD patients. We also discuss IFN-Ճ and IL-17 production from mucosal T cells and natural killer (NK) cells. Here, we show our recent findings about the plasticity of T helper cells in colitis. Th 17 cells express T-bet, and finally lose the expression of retinoic acid-related orphan receptor (ROR)Ճt, the master regulator of Th 17 cells, and are differentiated 'alternative Th 1 cells.' In addition to Th 1 cells, mucosal NK cells are also important sources of IFN-Ճ. Some of our ideas may be provocative, but we hope this review paper will provide new and firm understanding of the pathogenesis of IBD. (Intest Res 2012;10:317-323)

Citations

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