Fusobacterium species are distinctly associated with patients with Lynch syndrome colorectal cancer
Felix Salim,
Sayaka Mizutani,
Satoshi Shiba,
Hiroyuki Takamaru,
Masayoshi Yamada,
Takeshi Nakajima,
Tatsuo Yachida,
Tomoyoshi Soga,
Yutaka Saito,
Shinji Fukuda,
Shinichi Yachida,
Takuji Yamada
Affiliations
Felix Salim
School of Life Science and Technology, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8550, Japan
Sayaka Mizutani
School of Life Science and Technology, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8550, Japan; Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan
Satoshi Shiba
Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan
Hiroyuki Takamaru
Endoscopy Division, National Cancer Center Hospital, Chuo-ku 104-0045, Tokyo, Japan
Masayoshi Yamada
Endoscopy Division, National Cancer Center Hospital, Chuo-ku 104-0045, Tokyo, Japan
Takeshi Nakajima
Endoscopy Division, National Cancer Center Hospital, Chuo-ku 104-0045, Tokyo, Japan
Tatsuo Yachida
Department of Gastroenterology & Neurology, Faculty of Medicine, Kagawa University, Miki-cho, Kagawa 761-0793, Japan
Tomoyoshi Soga
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan
Yutaka Saito
Endoscopy Division, National Cancer Center Hospital, Chuo-ku 104-0045, Tokyo, Japan
Shinji Fukuda
Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan; Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Kanagawa 210-0821, Japan; Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Laboratory for Regenerative Microbiology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan; Metagen, Inc., Tsuruoka, Yamagata 997-0052, Japan; Metagen Theurapeutics, Inc., Tsuruoka, Yamagata 997-0052, Japan
Shinichi Yachida
Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka 565-0871, Japan; Corresponding author
Takuji Yamada
School of Life Science and Technology, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8550, Japan; Metagen, Inc., Tsuruoka, Yamagata 997-0052, Japan; Metagen Theurapeutics, Inc., Tsuruoka, Yamagata 997-0052, Japan; digzyme, Inc., Minato-ku, Tokyo 105-0004, Japan; Corresponding author
Summary: Accumulating evidence demonstrates clear correlation between the gut microbiota and sporadic colorectal cancer (CRC). Despite this, there is limited understanding of the association between the gut microbiota and CRC in Lynch Syndrome (LS), a hereditary type of CRC. Here, we analyzed fecal shotgun metagenomic and targeted metabolomic of 71 Japanese LS subjects. A previously published Japanese sporadic CRC cohort, which includes non-LS controls, was utilized as a non-LS cohort (n = 437). LS subjects exhibited reduced microbial diversity and low-Faecalibacterium enterotypes compared to non-LS. Patients with LS-CRC had higher levels of Fusobacterium nucleatum and fap2. Differential fecal metabolites and functional genes suggest heightened degradation of lysine and arginine in LS-CRC. A comparison between LS and non-LS subjects prior to adenoma formation revealed distinct fecal metabolites of LS subjects. These findings suggest that the gut microbiota plays a more responsive role in CRC tumorigenesis in patients with LS than those without LS.
