Role of the bactericidal lectin RegIIIbeta in Salmonella gut infection

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08783
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including mycology)
• Research Institution: Kitasato University
• Principal Investigator: Miki Tsuyoshi 北里大学, 薬学部, 講師 (40398582)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗菌レクチン / サルモネラ / 腸炎 / バクテロイデス属細菌 / ビタミンB6

Outline of Final Research Achievements

The bactericidal lectin RegIIIbeta is believed to be an immune effector, which protects from gut infection with bacterial pathogens. However, it was poorly understood how RegIIIbeta involves gut homeostasis by its bactericidal activity. In this study, we studied the role of RegIIIbeta in Salmonella gut infection by using the streptomycin mouse model for Salmonella diarrhea. Inducible expression of RegIIIbeta prolonged the Salmonella gut colonization and the enteropathy. RegIIIbeta also impacted the gut microbiota composition, which is characterized by suppression of Bacteroides spp. in the gut lumen. This dysbiosis can alter the colonic metabolism, resulting in reduced luminal vitamin B6 levels. Supplementation with Bacteroides app. or vitamin B6 accelerated Salmonella clearance from the gut and remission of enteropathy. Collectively, these findings suggest that RegIIIbeta does not act as a protective effector, rather unexpectedly helps Salmonella gut infection.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

本研究の研究結果はRegIIIbeta、バクテロイデス属細菌およびビタミンB6がサルモネラ腸炎の新たな治療ターゲットになる可能性を示した。近年、さまざまな疾患において、ディスバイオーシスが病態の増悪に関与することが報告されている。Clostridium difficile感染性腸炎に対する便細菌叢移植療法に代表されるように、腸内細菌叢および腸内環境の是正をめざしたアプローチは新たな治療法として、期待される。我々の研究知見は、ビタミンの産生能などを考慮した便細菌移植やビタミン投与の併用が、新たな治療法になる可能性を示唆する。