Elucidation of the mechanism of development of the intestinal environment via intestinal epithelial stem cell niche activity mediated by milk oligosaccharides.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19120
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 38:Agricultural chemistry and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Nakamura Kiminori 北海道大学, 先端生命科学研究院, 教授 (80381276)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: 母乳オリゴ糖 / 腸内環境 / 腸管上皮細胞 / Paneth細胞 / 幹細胞

Outline of Final Research Achievements

This study aims to elucidate the effects of breast milk oligosaccharides on intestinal epithelial stem cells and Paneth cells, which form the intestinal epithelial stem cell niche, and to develop novel disease prevention methods targeting the normalization of the intestinal environment. The results of live imaging analysis using intestinal epithelial enteroids and administration experiments in mice suggest that the direct active effect of oligosaccharides on the intestinal epithelial stem cell niche is involved in tissue formation and repair via the modulation of the intestinal microbiota. This study will contribute to the development of novel disease prevention methods targeting the intestinal epithelial stem cell niche.

Free Research Field

粘膜免疫

Academic Significance and Societal Importance of the Research Achievements

母乳中に含まれるオリゴ糖が乳児期の健全な腸内細菌叢形成を促し、子の将来のさまざまな疾病リスク軽減に寄与することが知られている。これまで母乳オリゴ糖の機能はビフィズス菌の選択的資化など共生側（細菌）の解析が中心に示されており、宿主側の腸管上皮細胞への作用は全く検討されていない。本研究の成果により、オリゴ糖の腸管上皮幹細胞ニッシェを形成する腸管上皮幹細胞とPaneth細胞に対する活性を介した腸内細菌叢形成および腸管組織形成への関与が示されたことで、腸管上皮幹細胞ニッシェ機能の活性化の誘導による腸内環境の正常化を標的とした、新規疾患予防法の開発が促進することが期待される。