{"id":403,"date":"2026-02-19T00:46:22","date_gmt":"2026-02-18T15:46:22","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/pub\/gh\/wp\/research\/research-detail\/research-group-9\/"},"modified":"2026-02-19T00:46:22","modified_gmt":"2026-02-18T15:46:22","slug":"research-group-9","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/pub\/gh\/en\/research\/research-detail\/research-group-9\/","title":{"rendered":"Inflammatory Bowel Disease (IBD) Group"},"content":{"rendered":"\n
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Inflammatory Bowel Disease (IBD) Group<\/h2>\n <\/div>\n\n
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Group Leader: Tsuyoshi Yoshihara<\/h2>\n

Concept: Research on pathophysiology and therapeutic strategies for gut-centered networks in the body<\/h3>\n

The IBD Group views the intestine not as a stand-alone organ, but as an \"information hub\" that supports homeostasis throughout the body. The intestinal mucosa, immune system, intestinal microbiota, and nervous system form a network that exchanges information with each other, and we believe that pathological conditions manifest as a breakdown of this linkage. Based on molecular-level analysis of cytokines, lipids, sugar chains, and enterobacterial metabolites, we are working to elucidate how inflammation is generated and regulated in the context of the linkage between the gut, the gut microbiota, and the gut and central nervous system. Through translational research that links the understanding of molecular mechanisms to biomarker development and optimization of therapeutic strategies, we aim to build precision medicine that approaches diseases from the viewpoint of intestinal networks.<\/p>\n <\/div>\n\n

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Construction of therapeutic strategies for inflammatory bowel disease (IBD) using biomarkers<\/h3>\n

While a wide variety of therapeutic agents are available for IBD, it remains a challenge to determine in advance which treatment is optimal for which patient. In this research, we are working on the development of biomarkers that visualize the characteristics of inflammation and immune response in the body using molecules in the blood and other body fluids. Based on the knowledge obtained from molecular mechanism research, we aim to predict therapeutic response and optimize treatment selection by identifying indicators that reflect differences in inflammation types and pathological conditions. As translational research integrating basic research and clinical data, our goal is to contribute to the realization of personalized medicine.<\/p>\n <\/div>\n\n

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Research on molecular mechanisms of IBD onset and exacerbation<\/h3>\n

In IBD, the regulation of immune responses in the intestinal mucosa is disrupted and chronic inflammation persists. In this study, we are analyzing the molecular mechanisms that determine the intensity and nature of inflammation from multiple angles, focusing not only on cytokines but also on molecules such as lipid mediators and glycosylation. These molecules are important signals that convey information between cells, and qualitative changes in these molecules are thought to be involved in the persistence of inflammation and the development of tissue damage. Through molecular analysis, we aim to elucidate how intestinal inflammation occurs and how it is amplified and regulated, and to identify new therapeutic targets and deepen our understanding of the pathogenesis of intestinal inflammation.<\/p>\n <\/div>\n\n

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Brain-Gut Correlation Study on Enteritis Control and Psychiatric Symptoms via the Nervous System<\/h3>\n

The intestine contains a highly developed neural network comparable to that of the brain, which interactively exchanges information with the central nervous system. In this research, we are conducting basic research to analyze the molecular and neural basis of how intestinal inflammation affects the nervous system and how the nervous system regulates intestinal inflammation. At the same time, we are focusing on psychiatric symptoms such as depression and anxiety seen in IBD patients and clinically evaluating the relationship between the state of intestinal inflammation and psychological symptoms. We are exploring the possibility of new treatment strategies that approach both intestinal inflammation and psychiatric symptoms from the viewpoint of inter-organ networks including the gut and brain, by elucidating how signals from the gut affect the whole body via the nervous system.<\/p>\n <\/div>\n\n

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Gut microbiota research and implementation of gut microbiota transplantation therapy (FMT)<\/h3>\n

The intestinal microbiota is considered to be a \u201cfunctional organ\u201d that is deeply involved in the regulation of immune responses and metabolic functions, while possessing genetic information that differs from that of the host. In this study, we focus on the interaction between intestinal bacteria and the intestinal mucosa, and conduct basic analysis of the relationship between bacterial metabolites and immune cells. We are also applying these findings to the development and exacerbation of intestinal inflammation and intestinal microbiota transplantation (FMT). We aim to establish a new treatment strategy based on microbiota intervention.<\/p>\n <\/div>\n <\/section>\n\n

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Future Prospects: From Elucidation of Molecular Mechanisms to Optimization of Patient-specific Therapy<\/h3>\n

The understanding of molecular mechanisms obtained from these studies is expected to lead to more sophisticated diagnosis and treatment selection. By establishing biomarkers in blood that reflect the quality of inflammation, we aim to visualize pathological conditions and realize personalized medicine that selects the optimal treatment for each patient. Furthermore, we will create new research seeds and elucidate disease mechanisms through basic research, starting from important clinical questions obtained from our abundant clinical experience. These findings will be connected to translational research to develop new treatments through interventional research such as intestinal microflora transplantation (FMT). We will accelerate the return to actual patient care through a research system that cycles between basic and clinical research.<\/p>\n <\/section>\n\n

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Major Papers<\/h3>\n
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  1. Yoshihara T, Shinzaki S, Amano T, Iijima H, Takehara T, Inoue N, Uchino M, Esaki M, Kobayashi T, Saruta M, Sugimoto K, Nakamura S, Hata K, Hirai F, Hiraoka S, Fujii T, Matsuura M, Matsuoka K, Watanabe K, Nakase H, Watanabe M. Fujii T, Matsuura M, Matsuoka K, Watanabe K, Nakase H, Watanabe M. Concomitant use of an immunomodulator with ustekinumab as an induction therapy for J Gastroenterol Hepatol. 2021 Jul;36(7):1744-1753. doi: 10.1111\/jgh.15401. Epub 2021 Feb 3. PMID: 33450096.<\/li>\n
  2. Nakahara M, Murayama Y, Kobayashi I, Kinoshita K, Ogawa H, Hiyama S, Shibukawa N, Komori M, Okuda Y, Kizu T, Yoshii S, Tsujii Y, Hayashi Y, Inoue T, Iijima H, Takehara T. Elderly onset age is associated with low efficacy of first anti-tumor necrosis factor treatment in patients with inflammatory bowel disease Sci Rep. 2022 Mar 29;12(1):5324. doi: 10.1038\/s41598-022-09455-8. PMID: 35351986; PMCID: PMC8964802.<\/li>\n
  3. Arimoto Y, Nakahara M, Murayama Y, Kobayashi I, Kinoshita K, Ogawa H, Hiyama S, Shibukawa N, Komori M, Okuda Y, Kizu T, Kitamura T, Kato M, Tsujii Y, Inoue T, Inoue T Iijima H, Hayashi Y, Takehara T. Effectiveness of tacrolimus therapy in refractory ulcerative colitis compared to infliximab with propensity score matching. Sci Rep. 2025 Jan 2;15(1):68. doi: 10.1038\/s41598-024-77365-y. PMID: 39747885; PMCID: PMC11696101.<\/li>\n
  4. Yoshihara T, Shinzaki S, Kawai S, Fujii H, Iwatani S, Yamaguchi T, Araki M, Hiyama S, Inoue T, Hayashi Y, Watabe K, Iijima H, Takehara T. Tissue Drug Concentrations of Anti-tumor Necrosis Factor Agents Are Associated with the Long-term Outcome of Patients with Crohn's Disease. Bowel Dis. 2017 Dec;23(12):2172-2179. doi: 10.1097\/MIB.00000000000000001260. doi: 28945638.<\/li>\n
  5. Current Status of Inflammatory Bowel Disease (IBD) Clinical Practice] Monitoring of Disease Activity in IBD Japanese Journal of Internal Medicine, 2025, Yoshihara T., Hayashi Y., Takehara T.<\/li>\n
  6. Nakase H, Uchino M, Shinzaki S, Matsuura M, Matsuoka K, Kobayashi T, Saruta M, Hirai F, Hata K, Hiraoka S, Esaki M, Sugimoto K, Fuji T, Watanabe K, Nakamura S, Inoue N, Itoh T, Naganuma M, Hisamatsu T, Watanabe M, Miwa H, Enomoto N, Shimosegawa T, Koike K. Inoue N, Itoh T, Naganuma M, Hisamatsu T, Watanabe M, Miwa H, Enomoto N, Shimosegawa T, Koike K. Evidence-based clinical practice guidelines for J Gastroenterol. 2021 Jun;56(6):489-526. doi: 10.1007\/s00535-021-01784-1. Epub 2021 Apr 22. PMID: 33885977; PMCID PMCID: 33885977; PMCID: PMC8137635.<\/li>\n
  7. Inflammatory Bowel Disease (IBD) Guidelines 2020 Author Shinichiro Shinzaki Collaborator Tsuyoshi Yoshihara<\/li>\n
  8. Iwatani S, Iijima H, Otake Y, Amano T, Tani M, Yoshihara T, Tashiro T, Tsujii Y, Inoue T, Hayashi Y, Takeda K, Hayashi A, Fujita S, Shinzaki S, Takehara T. Novel mass spectrometry-based comprehensive lipidomic analysis of plasma from patients with inflammatory bowel disease. 2020 Aug;35(8):1355-1364. doi: 10.1111\/jgh.15067. Epub 2020 Apr 23. PMID: 32285970.<\/li>\n
  9. Otake-Kasamoto Y, Kayama H, Kishikawa T, Shinzaki S, Tashiro T, Amano T, Tani M, Yoshihara T, Li B, Tani H, Liu L, Hayashi A, Okuzaki D, Motooka D, Nakamura S, Okada Y, Iijima H, Takeda K, Takehara T. Lysophosphatidylserines derived from microbiota in Crohn's disease elicit pathological Th1 Okada Y, Iijima H, Takeda K, Takehara T. Lysophosphatidylserines derived from microbiota in Crohn's disease elicit pathological Th1 J Exp Med. 2022 Jul 4;219(7):e20211291. doi: 10.1084\/jem.20211291. Epub 2022 May 24. PMID: 35608941; PMCID: PMC9134096.<\/li>\n
  10. Serada S, Fujimoto M, Terabe F, Iijima H, Shinzaki S, Matsuzaki S, Ohkawara T, Nezu R, Nakajima S, Kobayashi T, Plevy SE, Takehara T, Naka T. Serum leucine- Inflamm Bowel Dis. 2012 Nov;18(11):2169-79. doi: 10.1002\/ibd.22936. Epub 2012 Feb 28. PMID: 22374925.<\/li>\n
  11. Shinzaki S, Matsuoka K, Iijima H, Mizuno S, Serada S, Fujimoto M, Arai N, Koyama N, Morii E, Watanabe M, Hibi T, Kanai T, Takehara T, Naka T. Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis. J Crohns Colitis. 2017 Jan;11(1):84-91. doi: 10.1093\/ecco-jcc\/ jjw132. epub 2016 Jul 27. Erratum in: J Crohns Colitis. 2019 Dec 10;13(12):1590. doi: 10.1093\/ecco-jcc\/jjz100. PMID: 27466171; PMCID: PMC5175492.<\/li>\n
  12. Shinzaki S, Matsuoka K, Tanaka H, Takeshima F, Kato S, Torisu T, Ohta Y, Watanabe K, Nakamura S, Yoshimura N, Kobayashi T, Shiotani A, Hirai F, Hiraoka S, Watanabe M, Matsuura M, Nishimoto S, Mizuno S, Iijima H, Takehara T, Naka T, Kanai T, Matsumoto T. Watanabe M, Matsuura M, Nishimoto S, Mizuno S, Iijima H, Takehara T, Naka T, Kanai T, Matsumoto T. Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in J Gastroenterol. 2021 Jun;56(6):560-569. Epub 2021 May 3. PMID: 33942166; PMCID: PMC8137624.<\/li>\n
  13. Amano T, Yoshihara T, Shinzaki S, Sakakibara Y, Yamada T, Osugi N, Hiyama S, Murayama Y, Nagaike K, Ogiyama H, Yamaguchi T, Arimoto Y, Kobayashi I, Kawai S, Egawa S, Kizu T, Komori M, Tsujii Y, Asakura A, Tashiro T, Tani M, Otake-Kasamoto Y, Uema R, Kato M, Tsujii Y Egawa S, Kizu T, Komori M, Tsujii Y, Asakura A, Tashiro T, Tani M, Otake-Kasamoto Y, Uema R, Kato M, Tsujii Y, Inoue T, Yamada T, Kitamura T, Yonezawa A, Iijima H, Hayashi Y, Takehara T. Selection of anti-cytokine biologics by pretreatment levels of serum leucine-rich alpha-2 glycoprotein in patients with Sci Rep. 2024 Nov 29;14(1):29755. doi: 10.1038\/s41598-024-80285-6. PMID: 39613813; PMCID: PMC11607305.<\/li>\n
  14. Tashiro T, Shinzaki S, Yoshihara T, Tsujii Y, Asakura A, Amano T, Tani M, Otake-Kasamoto Y, Uema R, Tsujii Y, Inoue T, Ogino T, Iijima H, Hayashi Y, Takehara T Leucine-rich Alpha-2 glycoprotein could be clinically useful in active and postoperative Crohn's disease. PMID: 40091130; PMCID: PMC11911423.<\/li>\n
  15. Otake-Kasamoto Y, Shinzaki S, Hiyama S, Tashiro T, Amano T, Tani M, Yoshihara T, Inoue T, Kawai S, Yoshii S, Tsujii Y, Hayashi Y, Iijima H, Takehara T. Carbon dioxide insufflation reduces the relapse of ulcerative colitis after colonoscopy: A randomized controlled trial. PLoS One. 2023 Aug 17;18(8):e PMID: 37590283; PMCID: PMC10434883.<\/li>\n
  16. Otake-Kasamoto Y, Yoshihara T, Shinzaki S, Yamada T, Ogawa H, Sakakibara Y, Hiyama S, Tsujii Y, Asakura A, Tashiro T, Amano T, Tani M, Uema R, Tsujii Y, Inoue T, Iijima H, Hayashi Y, Takehara T. Safety and Effectiveness of Oral Budesonide after Endoscopic Balloon Dilation in Patients with Crohn's Disease: A Multicenter Prospective Intervention Study. Inflamm Intest Dis. 2025 Jul 30;10(1):254-264. doi: 10.1159\/000547608. PMID: 41537188; PMCID: PMC12799228.<\/li>\n
  17. Fujii H, Shinzaki S, Iijima H, Wakamatsu K, Iwamoto C, Sobajima T, Kuwahara R, Hiyama S, Hayashi Y, Takamatsu S, Uozumi N, Kamada Y, Tsujii M, Taniguchi N, Taniguchi N, Takehara T, Miyoshi E. Takehara T, Miyoshi E. Core Fucosylation on T Cells, Required for Activation of T-Cell Receptor Signaling and Induction of Colitis in Mice, Is Increased Gastroenterology. 2016 Jun;150(7):1620-1632. doi: 10.1053\/j.gastro.2016.03.002. epub 2016 Mar 8. PMID: 26965517.<\/li>\n
  18. Iwatani S, Shinzaki S, Amano T, Otake Y, Tani M, Yoshihara T, Tsujii Y, Hayashi Y, Inoue T, Okuzaki D, Mizushima T, Miyoshi E, Iijima H, Takehara T. Oligosaccharide-dependent anti-inflammatory role of galectin-1 for macrophages in ulcerative colitis. Epub 2020 Jul 6. PMID: 32424849.<\/li>\n
  19. Tani M, Shinzaki S, Asakura A, Tashiro T, Amano T, Otake-Kasamoto Y, Yoshihara T, Yoshii S, Tsujii Y, Hayashi Y, Inoue T, Motooka D, Nakamura S, Iijima H, Takehara T. Seasonal variations in gut microbiota and disease course in patients with inflammatory bowel disease. Takehara T. Seasonal variations in gut microbiota and disease course in patients with inflammatory bowel disease. PLoS One. 2023 Apr 18;18(4):e0283880 . doi: 10.1371\/journal.pone.0283880. PMID: 37071621; PMCID: PMC10112787.<\/li>\n
  20. Kusakabe S, Kurashige R, Fukushima K, Shimizu K, Yoshihara T, Motooka D, Nakamura S, Kurashige M, Nakata K, Hino A, Kasahara H, Ueda T, Fujita J, Hosen N, Hosen N Takehara T, Oda J. Fecal microbiota transplantation for Crohn's disease-like intestinal lesions arising after allogeneic stem cell transplantation. Int J Hematol. 2025 Nov;122(5):771-777. doi: 10.1007\/s12185-025-04049-2. Epub 2025 Aug 28. PMID: 40866789.<\/li>\n <\/ol>\n <\/section>\n\n <\/div>\n<\/main>","protected":false},"excerpt":{"rendered":"

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