2005 Fiscal Year Final Research Report Summary
A new therapeutic challenge for severe sepsis: intervention into the bacterial ecosystem in the digestive tract
| Project/Area Number |
16591553
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
SHIME Nobuaki Kyoto prefectural University of Medicine, Medical school, Assistant professor, 医学研究科, 助手 (00260795)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYA Takaaki Osaka University, Medical school, Associate professor, 微生物病研究所, 助教授 (80271633)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Sepsis / Innate immunity / Probiotics / Digestive tract / Commensal bacteria / Antibiotics |
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| Research Abstract |
Innate immunity is a primary immune system to remove invaded bacteria through various host inflammatory response. We investigated roles of digestive bacterial ecosystem in the innate immune response by using experimental severe infection models. First, we have evaluated significance of TLR-4 system, which is innate immune receptor for lipopolysaccharide(LPS), a virulent factor of gram-negative rods, with a mouse model of Pseudomonas aeruginosa pneumonia. A deficiency of TLR-4 receptor has resulted in severe lung injury and death, indicating that innate immune response via TLR-4 is indispensable for host defense system (Respiratory Res, 2004). Next, we have developed an in vitro system to assess responses in NODs family, another innate immune receptor, to evaluate the reaction of NOD system by various bacterial products. We then have developed an mouse model of depletion of bacterial flora from the digestive tract by administration of antimicrobials. In that model, the depletion of commensal bacterial flora was associated with suppressed immune response against LPS. The expression of TLR-4 receptors have been downregulated and the increases in plasma TNF-a level have been attenuated. We have concluded that commensal bacterial flora in the digestive tract contains a significant role to keep normal innate immune system. We are now proceeding to evaluate the changes in the innate immune response after the supplementation of probiotics, prebiotics, or synbiotics.
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