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 TakeuchiMakoto Suematsu, Naoko Ohtani, Yosuke Fukunaga, Masashi Ueno, Yoshiharu Sakai, Satoshi Nagayama, Eiji Hara

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Article number5674
JournalNature communications
Volume12
Issue number1
DOIs
Publication statusPublished - 2021 Dec

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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