Plasticity of host immune mechanisms and intestinal microbiota to be exposed to optimize fecal microbiota transplantation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07900
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kyorin University
• Principal Investigator: Matsuura Minoru 杏林大学, 医学部, 臨床教授 (30402910)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腸管微生物叢 / 免疫可塑性 / 糞便微生物移植

Outline of Final Research Achievements

We employed germ-free (GF) mice early in life (4 weeks of age) and later in life (10 weeks of age) for fecal microbiota transfer (FMT) from specific pathogen-free (SPF) mice. We performed age-unmatched FMT between recipients early in life and donors early or later in life, in addition to common age-matched FMT. Age-matched FMT resulted in significantly different bacterial compositions between recipients early vs. later in life. Age-unmatched FMT revealed that bacterial compositions of recipients from donors later in life were similar to those of recipients from donors early in life. Correlation analysis demonstrated that genera Lachnospiraceae NK4A136 group and Roseburia were positively correlated to genes expressed predominantly early in life. The characteristic gene expression of the intestinal mucosa early in life might contribute to select specific bacteria in the intestinal microbiome early in life.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

腸内細菌叢の乱れ(dysbiosis)が炎症性腸疾患(IBD)の発症や病態に関連することが報告され、微生物叢を標的としたIBD治療として糞便微生物移植(FMT)が注目されている。しかし、IBDにおけるFMTでは発症後のdysbiosisを改善しても背景にある宿主の免疫異常が是正されず、その効果は限定的である。本研究では健常な免疫発達に必要な腸管微生物叢に曝露すべき時期が幼少期にあり、幼少期の腸管環境に有利に生着する細菌群の存在とその生着に関与する腸管環境の特徴を明らかにした。本研究で得られた知見は現在のIBD治療としてのFMTが抱える課題を解決する糸口になる可能性がある。