School of Medicine, Department of Internal Medicine (Gastroenterology and Hepatology) (Shinanomachi)




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  • TH1 cell-inducing Escherichia coli strain identified from the small intestinal mucosa of patients with Crohn’s disease

    Nagayama M., Yano T., Atarashi K., Tanoue T., Sekiya M., Kobayashi Y., Sakamoto H., Miura K., Sunada K., Kawaguchi T., Morita S., Sugita K., Narushima S., Barnich N., Isayama J., Kiridooshi Y., Shiota A., Suda W., Hattori M., Yamamoto H., Honda K.

    Gut Microbes (Gut Microbes)     1 - 14 2020

    ISSN  19490976

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    © 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. Dysbiotic microbiota contributes to the pathogenesis of Crohn’s disease (CD) by regulating the immune system. Although pro-inflammatory microbes are probably enriched in the small intestinal (SI) mucosa, most studies have focused on fecal microbiota. This study aimed to examine jejunal and ileal mucosal specimens from patients with CD via double-balloon enteroscopy. Comparative microbiome analysis revealed that the microbiota composition of CD SI mucosa differs from that of non-CD controls, with an increased population of several families, including Enterobacteriaceae, Ruminococcaceae, and Bacteroidaceae. Upon anaerobic culturing of the CD SI mucosa, 80 bacterial strains were isolated, from which 9 strains representing 9 distinct species (Escherichia coli, Ruminococcus gnavus, Klebsiella pneumoniae, Erysipelatoclostridium ramosum, Bacteroides dorei, B. fragilis, B. uniformis, Parabacteroides distasonis, and Streptococcus pasteurianus) were selected on the basis of their significant association with CD. The colonization of germ-free (GF) mice with the 9 strains enhanced the accumulation of TH1 cells and, to a lesser extent, TH17 cells in the intestine, among which an E. coli strain displayed high potential to induce TH1 cells and intestinal inflammation in a strain-specific manner. The present results indicate that the CD SI mucosa harbors unique pro-inflammatory microbiota, including TH1 cell-inducing E. coli, which could be a potential therapeutic target.

  • Amino acid position 37 of HLA-DRβ1 affects susceptibility to Crohn's disease in Asians

    Han B., Akiyama M., Kim K.K., Oh H., Choi H., Lee C.H., Jung S., Lee H.S., Kim E.E., Cook S., Haritunians T., Yamazaki K., Park S.H., Ye B.D., McGovern D.P.B., Esaki M., Kawaguchi T., Khor S.S., Taylor K.D., Rotter J.I., Suzuki Y., Matsui T., Motoya S., Bang S.Y., Kim T.H., Momozawa Y., Kamatani Y., Tokunaga K., Kubo M., Okada Y., Yang S.K., Song K.

    Human Molecular Genetics (Human Molecular Genetics)  27 ( 22 ) 3901 - 3910 2018.11

    ISSN  09646906

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    © The Author(s) 2018. Published by Oxford University Press. All rights reserved. Crohn's disease (CD) and ulcerative colitis (UC) are the major types of chronic inflammatory bowel disease (IBD) characterized by recurring episodes of inflammation of the gastrointestinal tract. Although it is well established that human leukocyte antigen (HLA) is a major risk factor for IBD, it is yet to be determined which HLA alleles or amino acids drive the risks of CD and UC in Asians. To define the roles of HLA for IBD in Asians, we fine-mapped HLA in 12 568 individuals from Korea and Japan (3294 patients with CD, 1522 patients with UC and 7752 controls). We identified that the amino acid position 37 of HLA-DRβ1 plays a key role in the susceptibility to CD (presence of serine being protective, P = 3.6 × 10−67, OR = 0.48 [0.45-0.52]). For UC, we confirmed the known association of the haplotype spanning HLA-C∗12:02, HLA-B∗52:01 and HLA-DRB1∗1502 (P = 1.2 × 10−28, OR = 4.01 [3.14-5.12]).

  • Long-term retention of adalimumab treatment and associated prognostic factors for 1189 patients with Crohn's disease

    Tanaka H., Kamata N., Yamada A., Endo K., Fujii T., Yoshino T., Sugaya T., Yokoyama Y., Bamba S., Umeno J., Yanai Y., Ishii M., Kawaguchi T., Shinzaki S., Toya Y., Kobayashi T., Nojima M., Hibi T.

    Journal of Gastroenterology and Hepatology (Australia) (Journal of Gastroenterology and Hepatology (Australia))  33 ( 5 ) 1031 - 1038 2018.05

    ISSN  08159319

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    © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd Background and Aim: There are few studies on the long-term efficacy of adalimumab treatment for patients with Crohn's disease. We have conducted a large, multicenter, retrospective cohort study to evaluate the long-term retention rate and prognostic factors associated with the discontinuation of adalimumab treatment in patients with Crohn's disease. Methods: Data were collected from all patients with Crohn's disease who had received at least one induction dose of 160 mg of adalimumab between October 2010 and December 2013 at 41 institutions. The cumulative retention rates of adalimumab treatment following the first administration were estimated using the Kaplan–Meier method. Prognostic factors related to the cumulative retention rates were evaluated by log-rank tests and multivariate Cox regression analysis. Results: A total of 1189 patients were included in the study. The 1-, 2-, 3-, and 4-year cumulative retention rates of adalimumab were 81%, 72%, 65%, and 62%, respectively. The multivariate Cox regression analysis confirmed female sex, previous infliximab use, perianal disease, concomitant treatment with prednisolone at baseline, higher C-reactive protein levels, and lower albumin levels as significant independent predictors of poor retention rate of adalimumab treatment. Significantly, more female patients than male patients discontinued adalimumab because of adverse events, especially skin reactions, infections, and arthralgia. Conclusions: Our data demonstrated a good retention rate of adalimumab in patients with Crohn's disease over a 4-year period. Female sex, perianal disease, concomitant treatment with prednisolone at baseline, previous infliximab use, higher C-reactive protein levels, and lower albumin levels were associated with poor retention of adalimumab treatment.


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