Oral derived bacteria influence intestinal immune system

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15293
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Keio University
• Principal Investigator: Atarashi Koji 慶應義塾大学, 医学部(信濃町), 准教授 (60546787)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 腸内細菌 / Th1細胞 / クレブシエラ菌

Outline of Final Research Achievements

Intestinal colonization by bacteria of oral origin has been correlated with several gastrointestinal diseases, including inflammatory bowel diseases (IBD). However, a causal role of oral bacteria ectopically colonizing the intestine remains unclear. I inoculated saliva samples from IBD patients into germ-free (GF) mice by oral gavage. I have clarified that strains of Klebsiella spp. isolated from the salivary microbiota are strong inducers of T helper 1 (TH1) cells when they colonize the gut. Although these Klebsiella strains could not colonize the gut of SPF mice with normal microbiota, they preferentially colonize those of SPF mice with dysbiotic microbiota, such as antibiotics treatment. These Klebsiella strains elicit a severe gut inflammation in the context of a genetically susceptible host, such as Il10 deficient mice.

Free Research Field

粘膜免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、クローン病や潰瘍性大腸炎などの慢性炎症性腸疾患の発症に口腔由来のクレブシエラ属細菌が関与している可能性があることを明らかにした。これまでクレブシエラ菌が炎症性腸疾患に関与していることを示唆するデータは存在したが、直接の関与を証明した初めての結果であり、したがってクレブシエラ属細菌が慢性炎症性腸疾患に対する新たな創薬標的となり得ることが想定されます。そこで、クレブシエラ属細菌を選択的に排除・殺菌する抗生物質などの開発やクレブシエラ属細菌が腸管内に定着させないような薬剤の開発を通して、これら疾患の予防法や治療薬の開発につながることが期待できる。