Impeding Quorum Sensing Among the Intestinal Microbiota Impacts the Metastatic Rate of Colorectal Cancer
ABSTRACT Background The gut microbiota is associated with colorectal cancer (CRC) risk and CRC metastatic potential. However, the role of bacteria in CRC progression and metastasis remains unclear. Aims Here, we hypothesized that microbial communication, mediated through quorum sensing (QS), was a c...
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2025-06-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.71009 |
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| author | Matthew Dietz Travis J. Gates Rakesh Sikdar Subbaya Subramanian Mikael H. Elias Christopher Staley |
| author_facet | Matthew Dietz Travis J. Gates Rakesh Sikdar Subbaya Subramanian Mikael H. Elias Christopher Staley |
| author_sort | Matthew Dietz |
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| description | ABSTRACT Background The gut microbiota is associated with colorectal cancer (CRC) risk and CRC metastatic potential. However, the role of bacteria in CRC progression and metastasis remains unclear. Aims Here, we hypothesized that microbial communication, mediated through quorum sensing (QS), was a critical component regulating microbial functions related to cancer progression and metastasis. Materials & Methods To test this, male and female C57BL/6 mice were injected with organoids modeling aggressive colon cancer (CRC), carrying mutations in Apc, Kras, p53, and Smad4. Two groups of mice were treated with two different quorum quenching (QQ) lactonases (GcL or SsoPox) for 8 weeks (n = 10/group/sex). Fecal samples were collected weekly and characterized by Illumina next‐generation sequencing, with tissues collected during necropsy. Results Male mice treated with SsoPox had fewer metastases than control mice (χ2 = 3.206, p = 0.073), with no SsoPox‐treated male developing a metastasis. In contrast, female mice treated with SsoPox had more metastases than control mice (χ2 = 2.554, p = 0.110), and every female, SsoPox‐treated mouse that developed a primary tumor also developed metastasis by the experimental endpoint. However, QQ treatment was shown to minimally affect the gut microbiome composition. Similarly, no significant differences were observed in inflammatory response as assessed by immunofluorescent staining or fecal concentrations of immunoglobulin A, calprotectin, or lipocalin‐2. Differences in fecal short‐chain fatty acid concentrations also did not differ significantly. Discussion These results suggest that QQ treatment has a sex‐based effect on CRC metastatic rate. Conclusion Targeting communication among the gut microbiome may be a promising avenue for the development of CRC therapies that minimally impact microbial community composition and host immune response. |
| format | Article |
| id | doaj-art-fd4e4d64d79644f7bd73d078ba3f585d |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-fd4e4d64d79644f7bd73d078ba3f585d2025-08-20T03:26:34ZengWileyCancer Medicine2045-76342025-06-011412n/an/a10.1002/cam4.71009Impeding Quorum Sensing Among the Intestinal Microbiota Impacts the Metastatic Rate of Colorectal CancerMatthew Dietz0Travis J. Gates1Rakesh Sikdar2Subbaya Subramanian3Mikael H. Elias4Christopher Staley5Division of Basic and Translational Research, Department of Surgery University of Minnesota Minneapolis Minnesota USADivision of Basic and Translational Research, Department of Surgery University of Minnesota Minneapolis Minnesota USABioTechnology Institute, University of Minnesota St. Paul Minnesota USADivision of Basic and Translational Research, Department of Surgery University of Minnesota Minneapolis Minnesota USABioTechnology Institute, University of Minnesota St. Paul Minnesota USADivision of Basic and Translational Research, Department of Surgery University of Minnesota Minneapolis Minnesota USAABSTRACT Background The gut microbiota is associated with colorectal cancer (CRC) risk and CRC metastatic potential. However, the role of bacteria in CRC progression and metastasis remains unclear. Aims Here, we hypothesized that microbial communication, mediated through quorum sensing (QS), was a critical component regulating microbial functions related to cancer progression and metastasis. Materials & Methods To test this, male and female C57BL/6 mice were injected with organoids modeling aggressive colon cancer (CRC), carrying mutations in Apc, Kras, p53, and Smad4. Two groups of mice were treated with two different quorum quenching (QQ) lactonases (GcL or SsoPox) for 8 weeks (n = 10/group/sex). Fecal samples were collected weekly and characterized by Illumina next‐generation sequencing, with tissues collected during necropsy. Results Male mice treated with SsoPox had fewer metastases than control mice (χ2 = 3.206, p = 0.073), with no SsoPox‐treated male developing a metastasis. In contrast, female mice treated with SsoPox had more metastases than control mice (χ2 = 2.554, p = 0.110), and every female, SsoPox‐treated mouse that developed a primary tumor also developed metastasis by the experimental endpoint. However, QQ treatment was shown to minimally affect the gut microbiome composition. Similarly, no significant differences were observed in inflammatory response as assessed by immunofluorescent staining or fecal concentrations of immunoglobulin A, calprotectin, or lipocalin‐2. Differences in fecal short‐chain fatty acid concentrations also did not differ significantly. Discussion These results suggest that QQ treatment has a sex‐based effect on CRC metastatic rate. Conclusion Targeting communication among the gut microbiome may be a promising avenue for the development of CRC therapies that minimally impact microbial community composition and host immune response.https://doi.org/10.1002/cam4.71009autoinducermicrobiomeorganoidquorum quenchingsignaling |
| spellingShingle | Matthew Dietz Travis J. Gates Rakesh Sikdar Subbaya Subramanian Mikael H. Elias Christopher Staley Impeding Quorum Sensing Among the Intestinal Microbiota Impacts the Metastatic Rate of Colorectal Cancer Cancer Medicine autoinducer microbiome organoid quorum quenching signaling |
| title | Impeding Quorum Sensing Among the Intestinal Microbiota Impacts the Metastatic Rate of Colorectal Cancer |
| title_full | Impeding Quorum Sensing Among the Intestinal Microbiota Impacts the Metastatic Rate of Colorectal Cancer |
| title_fullStr | Impeding Quorum Sensing Among the Intestinal Microbiota Impacts the Metastatic Rate of Colorectal Cancer |
| title_full_unstemmed | Impeding Quorum Sensing Among the Intestinal Microbiota Impacts the Metastatic Rate of Colorectal Cancer |
| title_short | Impeding Quorum Sensing Among the Intestinal Microbiota Impacts the Metastatic Rate of Colorectal Cancer |
| title_sort | impeding quorum sensing among the intestinal microbiota impacts the metastatic rate of colorectal cancer |
| topic | autoinducer microbiome organoid quorum quenching signaling |
| url | https://doi.org/10.1002/cam4.71009 |
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