Development of new therapies using outer membrane vesicles derived from gut microbiota

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21603
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Kobe University
• Principal Investigator: Yamashita Tomoya 神戸大学, 医学部附属病院, 准教授 (90437468)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 腸内細菌外膜小胞 / 菌体毒素

Outline of Final Research Achievements

The purpose of this study is to elucidate the biological effects of outer membrane vesicles (OMVs) derived from gut microbiota and to verify their potential application to therapy. OMVs are spherical vesicles secreted by bacteria with a lipid bilayer structure of the diameter from 20 to 250 nm, and contain various bacterial cell components including lipopolysaccharide (LPS), proteins and nucleic acids of each bacterium.
We succeeded in isolating OMVs produced from cultured gut microbiota. LPS is contained in OMVs, and the pro-inflammatory activities were the same as LPS activity of each bacterium. It was confirmed that specific OMVs were produced from each bacterium. We investigated the transfer of OMVs from the intestinal tract to the blood, but we concluded that the possibility of transfer was low. Taken these, we could clarify the pathophysiological role of OMVs in vivo.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

腸内細菌が、どのような機序で宿主の生体機能に影響を及ぼしているのかということが注目されて研究が進められている。その中で、本研究課題では、腸内細菌の産生する外膜小胞OMVsの役割を検証した。我々の研究の成果として、少なくともOMVsが、腸管内から血液中に移行して、生体内で作用している可能性は低いことが示され、この機序での作用は無いことが示され、学術的には意義のある成果である。しかし、OMVsの腸上皮細胞への直接作用や、菌同志の作用を介して、宿主の生体作用に影響していることまでは検証できていない。