Keystone pathobionts associated with colorectal cancer promote oncogenic reprograming.
Fusobacterium nucleatum (Fn) and enterotoxigenic Bacteroides fragilis (ETBF) are two pathobionts consistently enriched in the gut microbiomes of patients with colorectal cancer (CRC) compared to healthy counterparts and frequently observed for their direct association within tumors. Although several...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297897&type=printable |
| _version_ | 1827339615501025280 |
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| author | Josh Jones Qiaojuan Shi Rahul R Nath Ilana L Brito |
| author_facet | Josh Jones Qiaojuan Shi Rahul R Nath Ilana L Brito |
| author_sort | Josh Jones |
| collection | DOAJ |
| description | Fusobacterium nucleatum (Fn) and enterotoxigenic Bacteroides fragilis (ETBF) are two pathobionts consistently enriched in the gut microbiomes of patients with colorectal cancer (CRC) compared to healthy counterparts and frequently observed for their direct association within tumors. Although several molecular mechanisms have been identified that directly link these organisms to features of CRC in specific cell types, their specific effects on the epithelium and local immune compartment are not well-understood. To fill this gap, we leveraged single-cell RNA sequencing (scRNA-seq) on wildtype mice and mouse model of CRC. We find that Fn and ETBF exacerbate cancer-like transcriptional phenotypes in transit-amplifying and mature enterocytes in a mouse model of CRC. We also observed increased T cells in the pathobiont-exposed mice, but these pathobiont-specific differences observed in wildtype mice were abrogated in the mouse model of CRC. Although there are similarities in the responses provoked by each organism, we find pathobiont-specific effects in Myc-signaling and fatty acid metabolism. These findings support a role for Fn and ETBF in potentiating tumorigenesis via the induction of a cancer stem cell-like transit-amplifying and enterocyte population and the disruption of CTL cytotoxic function. |
| first_indexed | 2024-03-07T20:03:09Z |
| format | Article |
| id | doaj.art-7f03280924d84d9ab20a07cc24b1b89d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-07T20:03:09Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7f03280924d84d9ab20a07cc24b1b89d2024-02-28T05:31:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01192e029789710.1371/journal.pone.0297897Keystone pathobionts associated with colorectal cancer promote oncogenic reprograming.Josh JonesQiaojuan ShiRahul R NathIlana L BritoFusobacterium nucleatum (Fn) and enterotoxigenic Bacteroides fragilis (ETBF) are two pathobionts consistently enriched in the gut microbiomes of patients with colorectal cancer (CRC) compared to healthy counterparts and frequently observed for their direct association within tumors. Although several molecular mechanisms have been identified that directly link these organisms to features of CRC in specific cell types, their specific effects on the epithelium and local immune compartment are not well-understood. To fill this gap, we leveraged single-cell RNA sequencing (scRNA-seq) on wildtype mice and mouse model of CRC. We find that Fn and ETBF exacerbate cancer-like transcriptional phenotypes in transit-amplifying and mature enterocytes in a mouse model of CRC. We also observed increased T cells in the pathobiont-exposed mice, but these pathobiont-specific differences observed in wildtype mice were abrogated in the mouse model of CRC. Although there are similarities in the responses provoked by each organism, we find pathobiont-specific effects in Myc-signaling and fatty acid metabolism. These findings support a role for Fn and ETBF in potentiating tumorigenesis via the induction of a cancer stem cell-like transit-amplifying and enterocyte population and the disruption of CTL cytotoxic function.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297897&type=printable |
| spellingShingle | Josh Jones Qiaojuan Shi Rahul R Nath Ilana L Brito Keystone pathobionts associated with colorectal cancer promote oncogenic reprograming. PLoS ONE |
| title | Keystone pathobionts associated with colorectal cancer promote oncogenic reprograming. |
| title_full | Keystone pathobionts associated with colorectal cancer promote oncogenic reprograming. |
| title_fullStr | Keystone pathobionts associated with colorectal cancer promote oncogenic reprograming. |
| title_full_unstemmed | Keystone pathobionts associated with colorectal cancer promote oncogenic reprograming. |
| title_short | Keystone pathobionts associated with colorectal cancer promote oncogenic reprograming. |
| title_sort | keystone pathobionts associated with colorectal cancer promote oncogenic reprograming |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297897&type=printable |
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