Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients
Background: Several studies suggest a role of gut microbiota in colorectal cancer (CRC) initiation and progression. Vitamin D (vitD) blood levels are also inversely correlated with CRC risk and prognosis. However, these factors’ interplay remains unknown. Methods: 74 CRC patients after standard trea...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558622000689 |
| _version_ | 1828213658158628864 |
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| author | Federica Bellerba Davide Serrano Johansson Harriet Chiara Pozzi Nicola Segata Amir NabiNejad Elisa Piperni Patrizia Gnagnarella Debora Macis Valentina Aristarco Chiara A. Accornero Paolo Manghi Aliana Guerrieri Gonzaga Roberto Biffi Luca Bottiglieri Cristina Trovato Maria Giulia Zampino Federica Corso Rino Bellocco Sara Raimondi Maria Rescigno Sara Gandini |
| author_facet | Federica Bellerba Davide Serrano Johansson Harriet Chiara Pozzi Nicola Segata Amir NabiNejad Elisa Piperni Patrizia Gnagnarella Debora Macis Valentina Aristarco Chiara A. Accornero Paolo Manghi Aliana Guerrieri Gonzaga Roberto Biffi Luca Bottiglieri Cristina Trovato Maria Giulia Zampino Federica Corso Rino Bellocco Sara Raimondi Maria Rescigno Sara Gandini |
| author_sort | Federica Bellerba |
| collection | DOAJ |
| description | Background: Several studies suggest a role of gut microbiota in colorectal cancer (CRC) initiation and progression. Vitamin D (vitD) blood levels are also inversely correlated with CRC risk and prognosis. However, these factors’ interplay remains unknown. Methods: 74 CRC patients after standard treatment were randomized to 1-year 2000 IU/day vitD or placebo. Baseline and post-treatment fecal microbiota for shotgun metagenomics sequencing was collected. Coda-lasso and Principal Component Analysis were used to select and summarize treatment-associated taxa and pathways. Associations between vitD and taxa/pathways were investigated with logistic regression. Mediation analysis was performed to study if treatment-associated taxa mediated the effect of supplementation on 25(OH)D levels. Cox proportional-hazards model was used for disease-free survival (DFS). Results: 60 patients were analyzed. Change in alpha diversity (Shannon: p = 0.77; Simpson: p = 0.63) and post-treatment beta diversity (p = 0.70) were comparable between arms. Post-treatment abundances of 63 taxa and 32 pathways differed between arms. The 63 taxa also mediated the effect of supplementation on 25(OH)D (p = 0.02). There were sex differences in vitD levels, microbiota and pathways. Pathways of essential amino acids’ biosynthesis were more abundant in supplemented women. Fusobacterium nucleatum presence at baseline was associated with worse DFS (p = 0.02). Those achieving vitD sufficiency (25(OH)D≥30 ng/ml) had lower post-treatment abundances (p = 0.05). Women were more likely to have F. nucleatum post-treatment (p = 0.02). Conclusions: VitD supplementation may contribute shaping the gut microbiota and the microbiota may partially mediate the effect of supplementation on 25(OH)D. The observed sex-specific differences highlight the necessity of including sex/gender as a variable in microbiome studies. |
| first_indexed | 2024-04-12T14:52:38Z |
| format | Article |
| id | doaj.art-7c5b154d6fb348ef9ba9d2ffa9fded50 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-04-12T14:52:38Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-7c5b154d6fb348ef9ba9d2ffa9fded502022-12-22T03:28:22ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862022-12-0134100842Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patientsFederica Bellerba0Davide Serrano1Johansson Harriet2Chiara Pozzi3Nicola Segata4Amir NabiNejad5Elisa Piperni6Patrizia Gnagnarella7Debora Macis8Valentina Aristarco9Chiara A. Accornero10Paolo Manghi11Aliana Guerrieri Gonzaga12Roberto Biffi13Luca Bottiglieri14Cristina Trovato15Maria Giulia Zampino16Federica Corso17Rino Bellocco18Sara Raimondi19Maria Rescigno20Sara Gandini21Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, ItalyDivision of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, Milan, Italy; Corresponding author at: Division of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141, Milan, Italy.Division of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, ItalyDepartment of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy; Department CIBIO, University of Trento, Trento, ItalyDepartment of Experimental Oncology, European Institute of Oncology IRCCS, Milan, ItalyDepartment of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy; Department CIBIO, University of Trento, Trento, ItalyDivision of Epidemiology and Biostatistics, European Institute of Oncology IRCCS, Milan, ItalyDivision of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, Milan, ItalyDivision of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, Milan, ItalyDivision of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, Milan, ItalyDepartment CIBIO, University of Trento, Trento, ItalyDivision of Cancer Prevention and Genetics, European Institute of Oncology IRCCS, Milan, ItalyUnit of Surgery of Peritoneal tumors, European Institute of Oncology IRCCS, Milan, ItalyDivision of Pathology, European Institute of Oncology IRCCS, Milan, ItalyDivision of Endoscopy, European Institute of Oncology IRCCS, Milan, ItalyDivision of Medical Oncology Gastrointestinal and Neuroendocrine tumors, European Institute of Oncology (IEO) IRCCS, Milan, ItalyDepartment of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy; Department of Mathematics (DMAT), Politecnico di Milano, Milan, Italy; Centre for Health Data Science (CHDS), Human Techonopole, Milan, ItalyDepartment of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenDepartment of Experimental Oncology, European Institute of Oncology IRCCS, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, ItalyDepartment of Experimental Oncology, European Institute of Oncology IRCCS, Milan, ItalyBackground: Several studies suggest a role of gut microbiota in colorectal cancer (CRC) initiation and progression. Vitamin D (vitD) blood levels are also inversely correlated with CRC risk and prognosis. However, these factors’ interplay remains unknown. Methods: 74 CRC patients after standard treatment were randomized to 1-year 2000 IU/day vitD or placebo. Baseline and post-treatment fecal microbiota for shotgun metagenomics sequencing was collected. Coda-lasso and Principal Component Analysis were used to select and summarize treatment-associated taxa and pathways. Associations between vitD and taxa/pathways were investigated with logistic regression. Mediation analysis was performed to study if treatment-associated taxa mediated the effect of supplementation on 25(OH)D levels. Cox proportional-hazards model was used for disease-free survival (DFS). Results: 60 patients were analyzed. Change in alpha diversity (Shannon: p = 0.77; Simpson: p = 0.63) and post-treatment beta diversity (p = 0.70) were comparable between arms. Post-treatment abundances of 63 taxa and 32 pathways differed between arms. The 63 taxa also mediated the effect of supplementation on 25(OH)D (p = 0.02). There were sex differences in vitD levels, microbiota and pathways. Pathways of essential amino acids’ biosynthesis were more abundant in supplemented women. Fusobacterium nucleatum presence at baseline was associated with worse DFS (p = 0.02). Those achieving vitD sufficiency (25(OH)D≥30 ng/ml) had lower post-treatment abundances (p = 0.05). Women were more likely to have F. nucleatum post-treatment (p = 0.02). Conclusions: VitD supplementation may contribute shaping the gut microbiota and the microbiota may partially mediate the effect of supplementation on 25(OH)D. The observed sex-specific differences highlight the necessity of including sex/gender as a variable in microbiome studies.http://www.sciencedirect.com/science/article/pii/S1476558622000689Colorectal cancerMicrobiomeMicrobiotaVitamin DSexGender |
| spellingShingle | Federica Bellerba Davide Serrano Johansson Harriet Chiara Pozzi Nicola Segata Amir NabiNejad Elisa Piperni Patrizia Gnagnarella Debora Macis Valentina Aristarco Chiara A. Accornero Paolo Manghi Aliana Guerrieri Gonzaga Roberto Biffi Luca Bottiglieri Cristina Trovato Maria Giulia Zampino Federica Corso Rino Bellocco Sara Raimondi Maria Rescigno Sara Gandini Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients Neoplasia: An International Journal for Oncology Research Colorectal cancer Microbiome Microbiota Vitamin D Sex Gender |
| title | Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients |
| title_full | Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients |
| title_fullStr | Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients |
| title_full_unstemmed | Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients |
| title_short | Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients |
| title_sort | colorectal cancer vitamin d and microbiota a double blind phase ii randomized trial colovid in colorectal cancer patients |
| topic | Colorectal cancer Microbiome Microbiota Vitamin D Sex Gender |
| url | http://www.sciencedirect.com/science/article/pii/S1476558622000689 |
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