Elucidation of the mechanisms of inflammation control by ED therapy for the pathological control of inflammatory bowel disease.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K14821
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: Kubota Atsuhito 北海道医療大学, 薬学部, 助教 (70879931)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 炎症性腸疾患 / 芳香族炭化水素受容体 / 成分栄養療法 / 制御性T細胞

Outline of Final Research Achievements

The pathogenesis of inflammatory bowel disease (IBD) has been reported to involve regulatory T cells（Treg） that suppress inflammation. Treg are induced by aromatic hydrocarbon receptors (AhR), and AhR activity was measured for several compounds and their metabolites in elemental diet (ED) using reporter cell lines. We found that metabolites of tryptophan, which are abundant in EDs, are potent agonists of the AhR. Its activity was 2-4 times higher than that of 5-ASA, a key drug in the treatment of IBD, and it was found to induce Tregs and suppress inflammation in animal models of IBD. These results suggest that EDs have an inflammation-regulating function as well as a conservative treatment.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

成分栄養療法（ED）は、IBDにおける消化管の保存的治療や栄養補充として経験的に用いられてきた。一方、近年の臨床論文ではEDに炎症制御作用を示唆するものが複数散見される。本研究では、EDに含まれるトリプトファンが生体内で代謝されAhRを介しTregを誘導する事を見出した。これは、EDがIBDの炎症を抑制し治療に貢献し得る事を示す基礎的エビデンスとなる。EDによる炎症制御機構が明らかになったことから、今後のIBD治療における成分栄養療法の立ち位置を変え、新たな薬物-栄養相互作用など発展的な研究の基礎となると予想する。