Biochemistry

Humans harbor over 100 trillion bacteria in the distal intestine. These commensal bacteria have long been appreciated for the benefits they provide to the host, the most obvious being their capacity to metabolize indigestible food components to small metabolites that are utilized as nutrients by host cells. Moreover, it is now clear that the presence of commensal bacteria contributes to shape the gut immune system though promoting the development of gut-associated lymphoid tissues (GALTs), the largest collection of secondary lymphoid organs, which are necessary for induction of mucosal IgA responses. To evoke the mucosal immune response, antigens on the mucosal surface must be transported across the epithelial barrier into GALT such as Peyer's patches. This function, called 'antigen transcytosis', is mediated by specialized epithelial M cells. We are currently conducting the studies to understand the molecular machinery by which intestinal M cells facilitate antigen transcytosis.

Certain enteric bacteria also facilitate differentiation of Th17 and Treg cells, both of which are major T cell populations in the intestinal mucosa. Thus, host-microbe interactions establish immunological homeostasis in the gut, which further raises the important question: how do commensal bacteria affect the host immune system? The intestinal microbiota constitutes a considerable bioreactor that ferments indigestible food substances (e.g., soluble dietary fibers and resistant starches) into various metabolites such as short-chain fatty acids (SCFAs). Notably, butyrate, a major SCFA, exert histone deacetylase (HDAC) inhibitory activity. We have shown that intestinal microbiota-derived butyrate contributes to establishing intestinal symbiosis by inducing Treg cells via the epigenetic mechanisms. Our laboratory aims to explore the epigenetic regulation of the immune system by intestinal microbiota, and also to elucidate the biological significance of this epigenetic regulation in immunity and metabolism.

Kimura I. et al., Science 367: eaaw8429, 2020.

Nagai M. et al., Cell 178: 1072-1087, 2019.

Furusawa Y. et al., Nature 504: 446-450, 2013.