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

Gut Microbes. 2020 Nov 9;12(1):1-20. doi: 10.1080/19490976.2020.1799733.

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.

Keywords: Colorectal cancer; MTT assay; cell proliferation; human microbiome; secretomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / genetics
  • Bacteria / pathogenicity
  • Bacterial Physiological Phenomena*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / pathology*
  • Gastrointestinal Microbiome / physiology*
  • Gastrointestinal Tract / microbiology*
  • Humans
  • Species Specificity
  • Virulence / genetics

Grant support

This work was supported by the Dutch Cancer Society (KWF; KUN 2015-7739). RT was supported by RIMLS grant 014-058. DRG was supported by CNPQ/BRASIL. BED was supported by the Netherlands Organization for Scientific Research (NWO) Vidi grant 864.14.004. AB was supported by NWO Veni grant 016.166.089.