Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients
Emerging evidence has suggested that dysbiosis of the gut microbiota may influence the drug efficacy of colorectal cancer (CRC) patients during cancer treatment by modulating drug metabolism and the host immune response. Moreover, gut microbiota can produce metabolites that may influence tumor proli...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9549 |
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| author | Lidia Sánchez-Alcoholado Aurora Laborda-Illanes Ana Otero Rafael Ordóñez Alicia González-González Isaac Plaza-Andrades Bruno Ramos-Molina Jaime Gómez-Millán María Isabel Queipo-Ortuño |
| author_facet | Lidia Sánchez-Alcoholado Aurora Laborda-Illanes Ana Otero Rafael Ordóñez Alicia González-González Isaac Plaza-Andrades Bruno Ramos-Molina Jaime Gómez-Millán María Isabel Queipo-Ortuño |
| author_sort | Lidia Sánchez-Alcoholado |
| collection | DOAJ |
| description | Emerging evidence has suggested that dysbiosis of the gut microbiota may influence the drug efficacy of colorectal cancer (CRC) patients during cancer treatment by modulating drug metabolism and the host immune response. Moreover, gut microbiota can produce metabolites that may influence tumor proliferation and therapy responsiveness. In this study we have investigated the potential contribution of the gut microbiota and microbial-derived metabolites such as short chain fatty acids and polyamines to neoadjuvant radiochemotherapy (RCT) outcome in CRC patients. First, we established a profile for healthy gut microbiota by comparing the microbial diversity and composition between CRC patients and healthy controls. Second, our metagenomic analysis revealed that the gut microbiota composition of CRC patients was relatively stable over treatment time with neoadjuvant RCT. Nevertheless, treated patients who achieved clinical benefits from RTC (responders, R) had significantly higher microbial diversity and richness compared to non-responder patients (NR). Importantly, the fecal microbiota of the R was enriched in butyrate-producing bacteria and had significantly higher levels of acetic, butyric, isobutyric, and hexanoic acids than NR. In addition, NR patients exhibited higher serum levels of spermine and acetyl polyamines (oncometabolites related to CRC) as well as zonulin (gut permeability marker), and their gut microbiota was abundant in pro-inflammatory species. Finally, we identified a baseline consortium of five bacterial species that could potentially predict CRC treatment outcome. Overall, our results suggest that the gut microbiota may have an important role in the response to cancer therapies in CRC patients. |
| first_indexed | 2024-03-10T08:10:02Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:10:02Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b788cb3c5f4d419b81faa917a35144ae2023-11-22T10:45:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012217954910.3390/ijms22179549Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer PatientsLidia Sánchez-Alcoholado0Aurora Laborda-Illanes1Ana Otero2Rafael Ordóñez3Alicia González-González4Isaac Plaza-Andrades5Bruno Ramos-Molina6Jaime Gómez-Millán7María Isabel Queipo-Ortuño8Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, SpainUnidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, SpainUnidad de Gestión Clínica de Oncología Radioterápica, Hospital Universitario Virgen de la Victoria, 29010 Málaga, SpainUnidad de Gestión Clínica de Oncología Radioterápica, Hospital Universitario Virgen de la Victoria, 29010 Málaga, SpainUnidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, SpainUnidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, SpainGrupo de Obesidad y Metabolismo, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), 30120 Murcia, SpainUnidad de Gestión Clínica de Oncología Radioterápica, Hospital Universitario Virgen de la Victoria, 29010 Málaga, SpainUnidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-CIMES-UMA, 29010 Málaga, SpainEmerging evidence has suggested that dysbiosis of the gut microbiota may influence the drug efficacy of colorectal cancer (CRC) patients during cancer treatment by modulating drug metabolism and the host immune response. Moreover, gut microbiota can produce metabolites that may influence tumor proliferation and therapy responsiveness. In this study we have investigated the potential contribution of the gut microbiota and microbial-derived metabolites such as short chain fatty acids and polyamines to neoadjuvant radiochemotherapy (RCT) outcome in CRC patients. First, we established a profile for healthy gut microbiota by comparing the microbial diversity and composition between CRC patients and healthy controls. Second, our metagenomic analysis revealed that the gut microbiota composition of CRC patients was relatively stable over treatment time with neoadjuvant RCT. Nevertheless, treated patients who achieved clinical benefits from RTC (responders, R) had significantly higher microbial diversity and richness compared to non-responder patients (NR). Importantly, the fecal microbiota of the R was enriched in butyrate-producing bacteria and had significantly higher levels of acetic, butyric, isobutyric, and hexanoic acids than NR. In addition, NR patients exhibited higher serum levels of spermine and acetyl polyamines (oncometabolites related to CRC) as well as zonulin (gut permeability marker), and their gut microbiota was abundant in pro-inflammatory species. Finally, we identified a baseline consortium of five bacterial species that could potentially predict CRC treatment outcome. Overall, our results suggest that the gut microbiota may have an important role in the response to cancer therapies in CRC patients.https://www.mdpi.com/1422-0067/22/17/9549colorectal cancergut microbiotaSCFAsgut permeabilityradiochemotherapytreatment outcome |
| spellingShingle | Lidia Sánchez-Alcoholado Aurora Laborda-Illanes Ana Otero Rafael Ordóñez Alicia González-González Isaac Plaza-Andrades Bruno Ramos-Molina Jaime Gómez-Millán María Isabel Queipo-Ortuño Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients International Journal of Molecular Sciences colorectal cancer gut microbiota SCFAs gut permeability radiochemotherapy treatment outcome |
| title | Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients |
| title_full | Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients |
| title_fullStr | Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients |
| title_full_unstemmed | Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients |
| title_short | Relationships of Gut Microbiota Composition, Short-Chain Fatty Acids and Polyamines with the Pathological Response to Neoadjuvant Radiochemotherapy in Colorectal Cancer Patients |
| title_sort | relationships of gut microbiota composition short chain fatty acids and polyamines with the pathological response to neoadjuvant radiochemotherapy in colorectal cancer patients |
| topic | colorectal cancer gut microbiota SCFAs gut permeability radiochemotherapy treatment outcome |
| url | https://www.mdpi.com/1422-0067/22/17/9549 |
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