Abstract A05: Growth rate alterations of human colorectal cancer cells by 157 gut bacteria

Abstract

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 effect on CRC cell growth. Five CRC cell lines and one noncancerous kidney cell line were selected based on their differences in mutational landscapes. 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 enhanced CRC cell growth, while most Fusobacteriaceae cells and secretomes inhibited growth, contrasting prior findings. For some bacterial families, strong cell line-dependent effects were obsevered, such as for Streptococcaceae and HT29 cells. In some bacteria, the presence of specific functional genes was associated with CRC cell growth rates, including the virulence genes TcdA 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 in ethanolamine utilization pathway. Together, our results reveal how different gut bacteria have wide-ranging effects on cancer cells, contribute a better understanding of the effects of the gut microbiome on the human host, and provide a valuable resource for identifying candidate target genes for potential microbiome-based diagnostics and treatment strategies. Citation Format: Rahwa Taddese, Daniel R. Garza, Lilian Ruiter, Clara Belzer, Steven Aalvink, Iris D. Nagtegaal, Bas E. Dutilh, Annemarie Boleij. Growth rate alterations of human colorectal cancer cells by 157 gut bacteria [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A05.