Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion

Shintaro Okumura, Yusuke Konishi, Megumi Narukawa, Yuki Sugiura, Shin Yoshimoto, Yuriko Arai, Shintaro Sato, Yasuo Yoshida, Shunya Tsuji, Ken Uemura, Masahiro Wakita, Tatsuyuki Matsudaira, Tomonori Matsumoto, Shimpei Kawamoto, Akiko Takahashi, Yoshiro Itatani, Hiroaki Miki, Manabu Takamatsu, Kazutaka Obama, Kengo Takeuchi, Makoto Suematsu, Naoko Ohtani, Yosuke Fukunaga, Masashi Ueno, Yoshiharu Sakai, Satoshi Nagayama () and Eiji Hara ()
Additional contact information
Shintaro Okumura: Research Institute for Microbial Diseases (RIMD), Osaka University
Yusuke Konishi: Research Institute for Microbial Diseases (RIMD), Osaka University
Megumi Narukawa: Research Institute for Microbial Diseases (RIMD), Osaka University
Yuki Sugiura: Keio University School of Medicine
Shin Yoshimoto: The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)
Yuriko Arai: The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)
Shintaro Sato: Research Institute for Microbial Diseases (RIMD), Osaka University
Yasuo Yoshida: School of Dentistry, Aichi Gakuin University
Shunya Tsuji: Research Institute for Microbial Diseases (RIMD), Osaka University
Ken Uemura: Research Institute for Microbial Diseases (RIMD), Osaka University
Masahiro Wakita: Immunology Frontier Research Centre (IFReC), Osaka University
Tatsuyuki Matsudaira: Research Institute for Microbial Diseases (RIMD), Osaka University
Tomonori Matsumoto: Research Institute for Microbial Diseases (RIMD), Osaka University
Shimpei Kawamoto: Research Institute for Microbial Diseases (RIMD), Osaka University
Akiko Takahashi: The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)
Yoshiro Itatani: Graduate School of Medicine, Kyoto University
Hiroaki Miki: Research Institute for Microbial Diseases (RIMD), Osaka University
Manabu Takamatsu: The Cancer Institute Hospital, JFCR
Kazutaka Obama: Graduate School of Medicine, Kyoto University
Kengo Takeuchi: The Cancer Institute, Japanese Foundation for Cancer Research (JFCR)
Makoto Suematsu: Keio University School of Medicine
Naoko Ohtani: Osaka City University Graduate School of Medicine
Yosuke Fukunaga: The Cancer Institute Hospital, JFCR
Masashi Ueno: The Cancer Institute Hospital, JFCR
Yoshiharu Sakai: Graduate School of Medicine, Kyoto University
Satoshi Nagayama: The Cancer Institute Hospital, JFCR
Eiji Hara: Research Institute for Microbial Diseases (RIMD), Osaka University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2 Porphyromonas species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the bacterial metabolite, butyrate. Notably, the invasion of these bacteria is observed in the CRC tissues, coinciding with the elevation of butyrate levels and signs of senescence-associated inflammatory phenotypes. Moreover, although the administration of these bacteria into ApcΔ14/+ mice accelerate the onset of colorectal tumours, this is not the case when bacterial butyrate-synthesis genes are disrupted. These results suggest a causal relationship between Porphyromonas species overgrowth and colorectal tumourigenesis which may be due to butyrate-induced senescence.

Date: 2021
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DOI: 10.1038/s41467-021-25965-x

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