REVIEW : Diet, microbiota, and inflammatory bowel disease: Lessons from Japanese foods

( Takanori Kanai ),( Katsuyoshi Matsuoka ),( Makoto Naganuma ),( Atsushi Hayashi ),( Tadakazu Hisamatsu ) 대한내과학회 2014 The Korean Journal of Internal Medicine Vol.29 No.4

The incidence and prevalence of inflammatory bowel diseases (IBDs) including ulcerative colitis and Crohn disease are rapidly increasing in Western countries and in developed Asian countries. Although biologic agents targeting the immune system have been effective in patients with IBD, cessation of treatment leads to relapse in the majority of patients, suggesting that intrinsic immune dysregulation is an effect, not a cause, of IBD. Dramatic changes in the environment, resulting in the dysregulated composition of intestinal microbiota or dysbiosis, may be associated with the fundamental causes of IBD. Japan now has upgraded water supply and sewerage systems, as well as dietary habits and antibiotic overuse that are similar to such features found in developed Western countries. The purpose of this review article was to describe the association of diet, particularly Japanese food and microbiota, with IBD.

Reviewing not Homer’s Iliad, but “Kai Bao Ben Cao”: indigo dye—the past, present, and future

Yusuke Yoshimatsu,Tomohisa Sujino,Takanori Kanai 대한장연구학회 2023 Intestinal Research Vol.21 No.2

Current new challenges in the management of ulcerative colitis

Tomohiro Fukuda,Makoto Naganuma,Takanori Kanai 대한장연구학회 2019 Intestinal Research Vol.17 No.1

Ulcerative colitis (UC) is a chronic inflammatory condition of the gastrointestinal tract. Although the cause of UC is postulatedto 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, amethod 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), andcalcineurin 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 humanmonoclonal anti-TNF-α antibody to be fabricated, anti α-4/β-7 integrin antibody, and Janus kinase inhibitor have been reportedto 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 herbalmedicine. We compared the features and efficacy of these new treatments. In this issue, the features and treatment options forthese new treatments is reviewed. (Intest Res 2019;17:36-44)

Recent trends in diagnostic techniques for inflammatory bowel disease

Makoto Naganuma,Naoki Hosoe,Takanori Kanai,Haruhiko Ogata 대한내과학회 2015 The Korean Journal of Internal Medicine Vol.30 No.3

Although ileocolonoscopy is the gold standard for diagnosis of inflammatory bowel disease and is useful for assessing the disease severity in the colon and terminal ileum, several alternative diagnostic techniques have been developed recently. For ulcerative colitis (UC), magnification colonoscopy, endocytoscopy, and confocal laser endomicroscopy enable assessment of histological inflammation without the need for biopsy. Capsule endoscopy is useful for detection of small intestinal and colonic lesions in both female and male patients. For UC, capsule endoscopy may be useful for evaluating colonic inflammation in patients with a previous poor colonoscopy experience, while it should be used only in Crohn’s disease (CD) patients with unexplained symptoms when other examinations are negative. Magnetic resonance enterography (MRE) is particularly useful for detecting transmural inflammation, stenosis, and extraintestinal lesions, including abscesses and fistulas. MRE is also useful when evaluating small and large intestinal lesions, even in cases with severe strictures in which full evaluation of the small bowel would be virtually impossible using other devices. Therefore, the appropriate diagnostic devices for detecting CD lesions in the small and large intestine should be used.

REVIEW : Immunological Abnormalities in the Pathogenesis of Inflammatory Bowel Disease

( Tadakazu Hisamatsu ),( Yohei Mikami ),( Katsuyoshi Matsuoka ),( Takanori Kanai ),( Toshifumi Hibi ) 대한장연구학회 2012 Intestinal Research Vol.10 No.4

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)-α. In addition, the CD14+ macrophages contributed to interferon (IFN)-γ production rather than IL-17 production by lamina propria mononuclear cells dependent on IL-23. We discuss herein this IL-23/IFN-γ-positive feedback loop in IBD patients. We also discuss IFN-γ 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)γt, 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-γ. 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)

Efficacy of Slow Nutrient Drinking Test for Evaluating Postprandial Distress Symptom in Japanese Patients With Functional Dyspepsia

Takahiro Watanabe,Tatsuhiro Masaoka,Hisako Kameyama,Takanori Kanai 대한소화기 기능성질환·운동학회 2022 Journal of Neurogastroenterology and Motility (JNM Vol.28 No.3

Background/AimsFunctional dyspepsia (FD), one of the functional gastrointestinal disorders, is highly prevalent. Impaired gastric accommodation is proposed as a pathophysiology of FD. In order to assess gastric accommodation, a slow nutrient drinking test was developed. This study aims to evaluate the effectiveness of this slow nutrient drinking test among patients with FD in Japan. MethodsAsymptomatic/healthy participants (n = 26) and those with FD (n = 16), were enrolled. An infusion pump was used to deliver the liquid meal into cups. They were requested to score their meal-related and abdominal symptoms at 5-minute intervals, using a 100 mm visual analog scale. They were instructed to end the test when they felt unable to ingest more or until after 50 minutes. ResultsThe test ending time was significantly shorter in patients with FD than in healthy participants (22.3 ± 10.6 vs 45.0 ± 7.5 minutes, P < 0.001). The receiver operating characteristic curve indicated that the optimal cutoff time for detecting patients with FD was 30 minutes. The severity of meal-related and abdominal symptoms between healthy participants and those with FD was continuously different. Univariate and multivariate analyses revealed that the presence of symptoms of postprandial distress syndrome contributed to the short test ending time. ConclusionThe 30-minute slow nutrient drinking test is a minimally invasive method of effectively evaluating symptoms of postprandial distress syndrome among patients with FD, in Japan.

Effects of the Oral Administration of Mosapride Citrate on Capsule Endoscopy Completion Rate

( Yosuke Ida ),( Naoki Hosoe ),( Hiroyuki Imaeda ),( Rieko Bessho ),( Riko Ichikawa ),( Makoto Naganuma ),( Takanori Kanai ),( Toshifumi Hibi ),( Haruhiko Ogata ) 대한소화기학회 2012 Gut and Liver Vol.6 No.3

Background/Aims: In capsule endoscopy (CE), the capsule does not always reach the cecum within its battery life, which may reduce its diagnostic yield. We evaluated the effect of mosapride citrate, a 5-hydroxytryptamine-4 agonist that increases gastrointestinal motility, on CE completion. Meth-ods: In a retrospective study, we performed univariate and multivariate analyses for 232 CE procedures performed at our hospital. To identify factors that affect CE completion, the following data were systematically collected: gender, age, gastric transit time (GTT), nonsteroidal anti-inflammatory drug administration, previous abdominal surgery, hospitaliza-tion, use of a polyethylene glycol solution, use of mosapride citrate (10 mg), body mass index (BMI), and total recording time. Results: The univariate analysis showed that oral mo-sapride citrate, GTT, and BMI were associated with improved CE completion. Multivariate analyses showed that oral mo-sapride citrate (odds ratio [OR], 1.99; 95% confidence inter-val [CI], 1.01 to 3.91) and GTT (OR, 2.34; 95% CI, 1.13 to 4.87) were significant factors for improving the CE completion. Oral mosapride citrate significantly shortened the GTT and small bowel transit time (SBTT). Conclusions: Oral mosapride ci-trate reduced the GTT and SBTT during CE and improved the CE completion rate. (Gut Liver 2012;6:339-343)

Colonic dysmotility and morphological abnormality frequently detected in Japanese patients with irritable bowel syndrome

( Takeshi Mizukami ),( Shinya Sugimoto ),( Tatsuhiro Masaoka ),( Hidekazu Suzuki ),( Takanori Kanai ) 대한장연구학회 2017 Intestinal Research Vol.15 No.2

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. (Intest Res 2017;15:236-243)

Risk Factors for Prolonged Hospital Stay after Endoscopy

Toshihiro Nishizawa,Shuntaro Yoshida,Osamu Toyoshima,Tatsuya Matsuno,Masataka Irokawa,Toru Arano,Hirotoshi Ebinuma,Hidekazu Suzuki,Takanori Kanai,Kazuhiko Koike 대한소화기내시경학회 2021 Clinical Endoscopy Vol.54 No.6

Background/Aims: The recovery room used after endoscopy has limited capacity, and an efficient flow of the endoscopy unitis desired. We investigated the duration of hospital stay after endoscopy and the risk factors for prolonged hospital stay amongoutpatients. Methods: We retrospectively studied consecutive patients who underwent esophagogastroduodenoscopy or colonoscopy at theToyoshima Endoscopy Clinic. We collected data on age, sex, body weight, midazolam and pethidine dosage, respiratory depressionduring endoscopy, and duration of hospital stay after endoscopy (scope out to check out). Risk factors for prolonged hospital stay (>100minutes) were identified using multiple logistic regression analysis. Results: We enrolled 3,898 patients, including 3,517 (90.2%) patients tested under sedation and 381 (9.8%) patients tested withoutsedation. Overall, 442 (11.3%) patients had prolonged stay (>100 min). The mean time difference between sedation group and nonsedationgroup was 44.2 minutes for esophagogastroduodenoscopy and 39.1 minutes for colonoscopy. Age (odds ratio [OR], 1.025;95% confidence interval [CI], 1.014−1.036), female sex (OR, 1.657; 95% CI, 1.220−2.249), and midazolam dose (OR, 1.019; 95% CI,1.013−1.026) were independently associated with prolonged hospital stay after esophagogastroduodenoscopy, with similar results forcolonoscopy. Conclusions: Old age, female sex, and midazolam dose were independent risk factors for prolonged hospital stay after endoscopy.

Pathophysiology of Potassium-competitive Acid Blocker-refractory Gastroesophageal Reflux and the Potential of Potassium-competitive Acid Blocker Test

( Tatsuhiro Masaoka ),( Hisako Kameyama ),( Tsuyoshi Yamane ),( Yuta Yamamoto ),( Hiroya Takeuchi ),( Hidekazu Suzuki ),( Yuko Kitagawa ),( Takanori Kanai ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.4

Background/Aims Potassium-competitive acid blockers are expected to be the next generation of drugs for the treatment of diseases caused by gastric acid. In 2015, vonoprazan fumarate, a novel potassium-competitive acid blocker, was approved by the Japanese health insurance system. Since its approval, patients refractory to vonoprazan can be encountered in clinical settings. We designed this study to clarify the pathophysiology of gastroesophageal reflux disease refractory to vonoprazan. Methods In this retrospective study, we involved patients who had refractory symptoms after administration of standard-dose proton pump inhibitors or vonoprazan and underwent diagnostic testing with esophageal high-resolution manometry and 24-hour multichannel intraluminal impedance and pH monitoring while using proton pump inhibitors or vonoprazan. Patients were diagnosed based on the Rome IV criteria for functional gastrointestinal disorders and diagnostic test results. Results Twenty-seven patients were analyzed during this study. Gastric pH ≥ 4 was sustained for a longer period of time, and the esophageal acid exposure time and number of acid reflux events were shorter in the vonoprazan group than in the proton pump inhibitor group. The percentage of patients diagnosed with acidic gastroesophageal reflux disease in the vonoprazan group was lower than that in the proton pump inhibitor group. Conclusions Intra-gastric pH and acid reflux were strongly suppressed by 20-mg vonoprazan. When patients with gastroesophageal reflux disease present symptoms after administration of 20-mg vonoprazan, the possibility of pathophysiologies other than acid reflux should be considered. (J Neurogastroenterol Motil 2018;24:577-583)