Growth rate alterations of human colorectal cancer cells by 157 gut bacteria

Rahwa Taddese, Daniel R. Garza, Lilian N. Ruiter, Marien I. de Jonge, Clara Belzer, Steven Aalvink, Iris D. Nagtegaal, Bas E. Dutilh, Annemarie Boleij*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Several bacteria in the human gut microbiome have been associated with colorectal cancer (CRC) by high-throughput screens. In some cases, molecular mechanisms have been elucidated that drive tumorigenesis, including bacterial membrane proteins or secreted molecules that interact with the human cancer cells. For most gut bacteria, however, it remains unknown if they enhance or inhibit cancer cell growth. Here, we screened bacteria-free supernatants (secretomes) and inactivated cells of over 150 cultured bacterial strains for their effects on cell growth. We observed family-level and strain-level effects that often differed between bacterial cells and secretomes, suggesting that different molecular mechanisms are at play. Secretomes of Bacteroidaceae, Enterobacteriaceae, and Erysipelotrichaceae bacteria enhanced cell growth, while most Fusobacteriaceae cells and secretomes inhibited growth, contrasting prior findings. In some bacteria, the presence of specific functional genes was associated with cell growth rates, including the virulence genes TcdA, TcdB in Clostridiales and FadA in Fusobacteriaceae, which both inhibited growth. Bacteroidaceae cells that enhanced growth were enriched for genes of the cobalamin synthesis pathway, while Fusobacteriaceae cells that inhibit growth were enriched for genes of the ethanolamine utilization pathway. Together, our results reveal how different gut bacteria have wide-ranging effects on cell growth, contribute a better understanding of the effects of the gut microbiome on host cells, and provide a valuable resource for identifying candidate target genes for potential microbiome-based diagnostics and treatment strategies.

Original languageEnglish
Number of pages20
JournalGut Microbes
Volume12
Issue number1
Early online date11 Sep 2020
DOIs
Publication statusPublished - 2020

Keywords

  • cell proliferation
  • Colorectal cancer
  • human microbiome
  • MTT assay
  • secretomes

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