Analysis on the structure-activity relation ship of the anti-inflammatory effect of exopolysaccharide produced by plant-derived lactic acid bacteria

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07099
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Hiroshima University
• Principal Investigator: Noda Masafumi 広島大学, 医系科学研究科(薬), 特任准教授 (40457289)
• Co-Investigator(Kenkyū-buntansha): 杉山 政則 広島大学, 医系科学研究科(薬), 共同研究講座教授 (30106801) ; 杉本 幸子 広島大学, 医系科学研究科(薬), 准教授 (60549012)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 細胞外多糖体 / 抗アレルギー / 抗炎症 / 肝機能改善 / 腸内細菌叢

Outline of Final Research Achievements

In the present study, we aimed to analyze the health-promoting effects of exopolysaccharide (EPS), which is produced by Lactobacillus IJH-SONE68 and has been reported to have anti-allergic and obesity effects, through the construction and characterization of its mutants generated by MNNG treatment.
Through animal disease model experiment, the result showed that one of the mutants, named M411 mutant, possessed sperior activities on anti-allergic disorder and improvement in hepatic parameters. Further, sequencing analysis on the EPS byisynthetic gene clusters, which are located on two different sites of the chromosomal DNA, was performed.
The result revealed that the single-point mutation (58C>T, L20F) was occurred in the Pce1C that is predicted to be a membrane protein participated in the polymerization step of a series of saccharide units in EPS biosynthesis.

Free Research Field

分子微生物学

Academic Significance and Societal Importance of the Research Achievements

本株の産生するEPSには、並行して実施していた臨床研究によっても同様の改善効果が認められ、また糞便細菌叢の解析結果から、指定難病である各種胆管炎の症状と相関性を示すAnaerostipes属細菌およびVeillonella disparの存在比率を、本EPSの摂取が改善する事も明らかとなった。加えて、本EPSは潰瘍性大腸炎モデルマウスの症状を予防・改善することも確認できた。
本研究成果から、ヒトと共生関係にある腸内細菌叢を創薬ターゲットとして捉える意義について改めて示すことができたと共に、未だ難治性の疾患であるいくつかの指定難病に対する新たな治療法開発の可能性を提唱することができたと考える。