Growth rate alterations of human colorectal cancer cells by 157 gut bacteria
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 cance...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-11-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/19490976.2020.1799733 |
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| author | Rahwa Taddese Daniel R. Garza Lilian N. Ruiter Marien I. de Jonge Clara Belzer Steven Aalvink Iris D. Nagtegaal Bas E. Dutilh Annemarie Boleij |
| author_facet | Rahwa Taddese Daniel R. Garza Lilian N. Ruiter Marien I. de Jonge Clara Belzer Steven Aalvink Iris D. Nagtegaal Bas E. Dutilh Annemarie Boleij |
| author_sort | Rahwa Taddese |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T23:12:39Z |
| format | Article |
| id | doaj.art-f25ba3873c0e4cd889ac7c69b2d9bde2 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-12-13T23:12:39Z |
| publishDate | 2020-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-f25ba3873c0e4cd889ac7c69b2d9bde22022-12-21T23:28:02ZengTaylor & Francis GroupGut Microbes1949-09761949-09842020-11-0112110.1080/19490976.2020.17997331799733Growth rate alterations of human colorectal cancer cells by 157 gut bacteriaRahwa Taddese0Daniel R. Garza1Lilian N. Ruiter2Marien I. de Jonge3Clara Belzer4Steven Aalvink5Iris D. Nagtegaal6Bas E. Dutilh7Annemarie Boleij8Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical CenterRadboud University Medical CenterRadboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical CenterRadboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical CenterWageningen University and ResearchWageningen University and ResearchRadboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical CenterRadboud University Medical CenterRadboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical CenterSeveral 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.http://dx.doi.org/10.1080/19490976.2020.1799733colorectal cancercell proliferationmtt assayhuman microbiomesecretomes |
| spellingShingle | Rahwa Taddese Daniel R. Garza Lilian N. Ruiter Marien I. de Jonge Clara Belzer Steven Aalvink Iris D. Nagtegaal Bas E. Dutilh Annemarie Boleij Growth rate alterations of human colorectal cancer cells by 157 gut bacteria Gut Microbes colorectal cancer cell proliferation mtt assay human microbiome secretomes |
| title | Growth rate alterations of human colorectal cancer cells by 157 gut bacteria |
| title_full | Growth rate alterations of human colorectal cancer cells by 157 gut bacteria |
| title_fullStr | Growth rate alterations of human colorectal cancer cells by 157 gut bacteria |
| title_full_unstemmed | Growth rate alterations of human colorectal cancer cells by 157 gut bacteria |
| title_short | Growth rate alterations of human colorectal cancer cells by 157 gut bacteria |
| title_sort | growth rate alterations of human colorectal cancer cells by 157 gut bacteria |
| topic | colorectal cancer cell proliferation mtt assay human microbiome secretomes |
| url | http://dx.doi.org/10.1080/19490976.2020.1799733 |
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