2023 Fiscal Year Final Research Report

New therapeutic strategy for inflammatory bowel disease and inflammatory carcinogenesis from breast milk-derived probiotics

Research Project

PDF

Project/Area Number	21K11699
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 59040:Nutrition science and health science-related
Research Institution	Kagawa University
Principal Investigator	Kurahara Lin 香川大学, 医学部, 准教授 (00341438)
Co-Investigator(Kenkyū-buntansha)	平石敬三福岡大学, 医学部, 助教 (60896413) 山下哲生香川大学, 医学部, 助教 (80444727) 松田陽子香川大学, 医学部, 教授 (20363187)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	母乳 / 炎症性腸疾患 / プロバイオティクス / 炎症性発癌 / ミルクオリゴ糖
Outline of Final Research Achievements	The longer the breastfeeding period, the lower is the risk of IBD. Prolonged IBD is one of the major risks related to colitis-associated cancer (CAC) development. Here, we investigated effects of the colostrum derived Lactobacillus rhamnosus M9 (Probio-M9) or milk oligosaccharide lactulose on CAC. CAC model mice showed weight loss, diarrhea, intestinal shortening, tumorigenesis, increased inflammation, fibrosis, increased macrophage cells in the subserosal layer of non-tumor areas. Probio-M9 or lactulose treatment upregulated fecal microbial diversity and reversed fecal microbial functions, and suppressed tumor formation by regulating inflammation. Furthermore, we found that co-culture of Probio-M9 ameliorated the LPS induced tight junction proteins down-regulation in Caco-2 cells. Probio-M9 has a gene sequence for L-rhamnose isomerase, the recombinant enzyme exhibits enzymatic activity even under acidic conditions, and X-ray crystal structure was successfully analyzed.
Free Research Field	病態生理学
Academic Significance and Societal Importance of the Research Achievements	医学雑誌「Lancet」は「Lancet Brestfeeding」シリーズを設け、母乳育児によって、腸炎をはじめとする多くの疾病の予防に繋がり、82万人の命を救うことができるという調査結果を発表した。母乳がどのような機序で腸管炎症の発症を抑制しているのか、母乳育児によって形成される腸内細菌叢が関与しているのか、さらには、母乳が治療的に有効であるかということに関しては、多くの不明な点が残されている。本研究は、炎症性発癌の観点から母乳由来プロバイオティックスやミルクオリゴ糖の治療効果の機序を、腸内細菌および腸管炎症に及ぼす影響を明らかにした。