September 30, 2020
Keio University School of Medicine
Japan Agency for Medical Research and Development
A research group led by Senior Lecturer Hitoshi Tsugawa, Associate Professor Yasunori Kabe, and Professor Makoto Suematsu of the Department of Biochemistry, Keio University School of Medicine, has successfully identified ASC, a novel receptor protein for short-chain fatty acids produced by gut bacteria. They discovered that the innate immune-activating effect mediated by this receptor provides a protective effect against infection by Salmonella, a cause of food poisoning.
Short-chain fatty acids are produced in large quantities when dietary fiber is metabolized by gut bacteria and are known to be involved in regulating various immune responses, but their detailed mechanism of action was not understood. In this study, using their proprietary drug receptor screening technology, the group successfully identified a human-derived receptor, apoptosis-associated speck-like protein (ASC), that specifically binds to short-chain fatty acids. ASC is known to function as an adaptor protein in the inflammasome complex. The group has now elucidated that short-chain fatty acids enhance the innate immune capacity of immunocompetent cells such as macrophages by activating ASC's ability to form inflammasomes. Furthermore, they found that this immune-activating effect contributes to protection against infection by Salmonella, a cause of food poisoning, and demonstrated that the intake of water-soluble dietary fiber, which is broken down in the gut to produce large amounts of short-chain fatty acids, significantly prolongs the survival of mice infected with Salmonella. These findings reveal a new regulatory mechanism by which short-chain fatty acids suppress Salmonella infection via inflammasome activation, and are expected to lead to the development of new therapeutic and preventive methods for protecting against pathogenic bacterial infections through the intake of components that generate short-chain fatty acids, such as dietary fiber.
This research was published in the online early edition of the scientific journal "PLoS Biology" on September 29, 2020 (Pacific Daylight Time).
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