Succinic semialdehyde derived from the gut microbiota can promote the proliferation of adult T-cell leukemia/lymphoma cells
Nodoka Chiba,
Shinya Suzuki,
Daniel Enriquez-Vera,
Atae Utsunomiya,
Yoko Kubuki,
Tomonori Hidaka,
Kazuya Shimoda,
Shingo Nakahata,
Takuji Yamada,
Kazuhiro Morishita
Affiliations
Nodoka Chiba
School of Life Science and Technology, Tokyo Institute of Technology, Meguro, Tokyo, Japan
Shinya Suzuki
School of Life Science and Technology, Tokyo Institute of Technology, Meguro, Tokyo, Japan
Daniel Enriquez-Vera
Division of HTLV-1/ATL Carcinogenesis and Therapeutics, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Sakuragaoka, Kagoshima, Japan
Atae Utsunomiya
Department of Hematology, Imamura General Hospital, Kamoikeshinmachi, Kagoshima, Japan
Yoko Kubuki
Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan
Tomonori Hidaka
Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan
Kazuya Shimoda
Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan
Shingo Nakahata
Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Kiyotake, Miyazaki, Japan; Division of HTLV-1/ATL Carcinogenesis and Therapeutics, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Sakuragaoka, Kagoshima, Japan; Corresponding author. Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Kiyotake, Miyazaki, Japan.
Takuji Yamada
School of Life Science and Technology, Tokyo Institute of Technology, Meguro, Tokyo, Japan; Metagen, Inc., Yamagata, Japan; Metagen Theurapeutics, Inc., Yamagata, Japan; digzyme, Inc., Tokyo, Japan; Corresponding author. School of Life Science and Technology, Tokyo Institute of Technology, Meguro, Tokyo, Japan.
Kazuhiro Morishita
Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Kiyotake, Miyazaki, Japan; Project for Advanced Medical Research and Development, Project Research Division, Frontier Science Research Center, University of Miyazaki, Kiyotake, Miyazaki, Japan; Corresponding author. Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, University of Miyazaki, Kiyotake, Miyazaki, Japan.
Adult T-cell leukemia/lymphoma (ATLL) is a refractory blood cancer with severe immunodeficiency resulting from retroviral infection. ATLL develops in only 5 % of HTLV-1-infected individuals, but the entire mechanism of ATLL progression remains unknown. Since recent studies have reported that the gut microbiome influences the progression of various diseases, we hypothesized that ATLL is also related to the gut microbiome and aimed to investigate this relationship.We analyzed the taxonomic and functional profiles of the gut microbiota of ATLL patients (n = 28) and HTLV-1-infected individuals (n = 37). We found that the succinic semialdehyde (SSA) synthesis pathway was significantly enriched in the gut microbiome of ATLL patients (P = 0.000682), and Klebsiella, whose abundance was significantly greater in ATLL patients and high-risk HTLV-1-infected individuals (P = 0.0326), was the main contributor to this pathway. Administration of SSAs to ATLL cell lines resulted in significant cell proliferation.Herein, we propose that the gut microbiome can regulate ATLL progression via metabolites.
