Organization

Division of Mucosal Symbiosis

Yoshiyuki Gotoh

The intestine is a unique organ which is exposed by countless numbers of external antigens including dietary molecules, commensal and pathogenic bacteria, fungi, parasites, and viruses. Especially, trillions of commensal bacteria peacefully colonize in the luminal cavity in the gut. In our intestinal tract, immune cells and epithelial cells construct a network system to protect against infection by harmful pathogens and create a symbiotic environment for non-pathogenic microbes that keep intestinal homeostasis. Recent works have shown that commensal microbes also play important roles in the induction of host intestinal immune systems such as IgA production, T cell differentiation, and epithelial barrier formation. The understanding interplay between commensal microbes and the immune system is therefore extremely important. In addition, disruption of homeostasis of gut microbiota, which is called dysbiosis, is a trigger for the development of various host diseases, such as inflammatory bowel diseases, metabolic syndrome, allergic diseases, cancer development, and neuronal disorders. In the context of the clinical application, commensal bacteria are also attractive therapeutic targets for the development of novel clinical approach against these diseases. Indeed, there is a possibility that identifying beneficial commensal bacteria may be associated with the development of microbiome drug for the treatment of various diseases.

The mission of our lab is “Understand and identify the mechanism of symbiosis between host and commensal bacteria and contribute to the development of novel therapeutic, prophylactic, and diagnostic approaches for commensal-related diseases.” In our laboratory, we clarify the induction and regulation mechanism of a1, 2-fucose, which is one of the symbiotic factors between the host and commensal bacteria. Through this study, we will elucidate the mechanism of intestinal homeostasis and pathogenesis. Intestinal bacteria are also involved not only in the induction of a1, 2-fucose expressed on intestinal epithelial cells but also in the differentiation and functional maturation of intestinal immune cells such as T cells and IgA+ cells. We focus on intestinal Th17 cells and group 3 innate lymphocytes (ILC3) for a better understanding of microbiota-immune cell interaction and the mechanism of intestinal homeostasis. Furthermore, various microorganisms such as fungi and viruses as well as bacteria reside in the intestine. It is almost unclear how these microorganisms interact with intestinal bacteria and their hosts. In our laboratory, we investigate the interaction between bacteria and fungi. We also identify the mechanisms of colonization resistance by commensal bacteria against infection by pathogenic microorganisms and how they are involved in host pathogenesis (e.g., inflammatory bowel disease, metabolic syndrome, cancer, etc.) at the molecular, cellular, and organismal level.

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