2021/03/04
Keio University School of Medicine
Central Institute for Experimental Animals
Japan Agency for Medical Research and Development (AMED)
A research group from the Department of Pharmacology, Keio University School of Medicine, led by Project Assistant Professor Masaki Suzuki, Senior Lecturer Junpei Sasabe, and Professor Masato Yasui, has discovered that the metabolism of D-amino acids derived from gut bacteria regulates the host's intestinal immunity. This was a joint research project with Professor Takanori Kanai from the Department of Internal Medicine (Gastroenterology) at the same university, Professor Matthew Waldor from Harvard Medical School in the US, Director Mamoru Ito from the Central Institute for Experimental Animals, and Professor Kenji Hamase from the Graduate School of Pharmaceutical Sciences at Kyushu University.
Gut bacteria that inhabit the digestive tract of mammals produce a variety of metabolites. Mammals, including humans, recognize these bacterial metabolites and structural fragments, maintaining a symbiotic balance with the bacteria by mounting an appropriate immune response. Interestingly, bacteria use D-amino acids—metabolites that mammals cannot produce—to build their own outer wall structures. However, it was not known how these D-amino acids, which are characteristic of bacteria, affect the mammalian immune system, nor what significance they have for the symbiotic relationship between mammals and bacteria.
In this study, the research group discovered that a mammalian enzyme that specifically recognizes and degrades D-amino acids regulates the quantity and quality of immunoglobulin A (IgA), thereby modulating the symbiosis with bacteria.
IgA is the main immunoglobulin that forms the mucosal barrier, playing a role in regulating the symbiotic relationship with gut bacteria and protecting the body from infection by pathogenic bacteria and viruses. When the mammalian D-amino acid metabolic enzyme loses its function, the gut flora is disrupted, and D-amino acids increase. In response, it was found that macrophages and B lymphocytes, which are responsible for immunity, are activated to increase IgA production, leading to an excessive reaction against the gut flora. In other words, it was revealed that the host (humans) regulates immunity by recognizing D-amino acids synthesized by gut bacteria, thereby maintaining a symbiotic relationship with them. Disruptions in the symbiotic relationship between humans and bacteria are increasingly being shown to be involved in various diseases of the immune, metabolic, and nervous systems. It is hoped that the advancement of this research will lead to a better understanding of diseases caused by disruptions in symbiotic bacteria and the development of new therapeutic targets.
The results of this research were published in the online edition of the international multidisciplinary journal "Science Advances" on March 3, 2021 (US Eastern Time).
For the full press release, please see below.