Gut microbiota composition in colorectal cancer patients is genetically regulated
Abstract The risk of colorectal cancer (CRC) depends on environmental and genetic factors. Among environmental factors, an imbalance in the gut microbiota can increase CRC risk. Also, microbiota is influenced by host genetics. However, it is not known if germline variants influence CRC development b...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15230-6 |
| _version_ | 1811224105029992448 |
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| author | Francesca Colombo Oscar Illescas Sara Noci Francesca Minnai Giulia Pintarelli Angela Pettinicchio Alberto Vannelli Luca Sorrentino Luigi Battaglia Maurizio Cosimelli Tommaso A. Dragani Manuela Gariboldi |
| author_facet | Francesca Colombo Oscar Illescas Sara Noci Francesca Minnai Giulia Pintarelli Angela Pettinicchio Alberto Vannelli Luca Sorrentino Luigi Battaglia Maurizio Cosimelli Tommaso A. Dragani Manuela Gariboldi |
| author_sort | Francesca Colombo |
| collection | DOAJ |
| description | Abstract The risk of colorectal cancer (CRC) depends on environmental and genetic factors. Among environmental factors, an imbalance in the gut microbiota can increase CRC risk. Also, microbiota is influenced by host genetics. However, it is not known if germline variants influence CRC development by modulating microbiota composition. We investigated germline variants associated with the abundance of bacterial populations in the normal (non-involved) colorectal mucosa of 93 CRC patients and evaluated their possible role in disease. Using a multivariable linear regression, we assessed the association between germline variants identified by genome wide genotyping and bacteria abundances determined by 16S rRNA gene sequencing. We identified 37 germline variants associated with the abundance of the genera Bacteroides, Ruminococcus, Akkermansia, Faecalibacterium and Gemmiger and with alpha diversity. These variants are correlated with the expression of 58 genes involved in inflammatory responses, cell adhesion, apoptosis and barrier integrity. Genes and bacteria appear to be involved in the same processes. In fact, expression of the pro-inflammatory genes GAL, GSDMD and LY6H was correlated with the abundance of Bacteroides, which has pro-inflammatory properties; abundance of the anti-inflammatory genus Faecalibacterium correlated with expression of KAZN, with barrier-enhancing functions. Both the microbiota composition and local inflammation are regulated, at least partially, by the same germline variants. These variants may regulate the microenvironment in which bacteria grow and predispose to the development of cancer. Identification of these variants is the first step to identifying higher-risk individuals and proposing tailored preventive treatments that increase beneficial bacterial populations. |
| first_indexed | 2024-04-12T08:43:25Z |
| format | Article |
| id | doaj.art-f1e84126118f48a79e77286d07af34f2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T08:43:25Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f1e84126118f48a79e77286d07af34f22022-12-22T03:39:47ZengNature PortfolioScientific Reports2045-23222022-07-0112111210.1038/s41598-022-15230-6Gut microbiota composition in colorectal cancer patients is genetically regulatedFrancesca Colombo0Oscar Illescas1Sara Noci2Francesca Minnai3Giulia Pintarelli4Angela Pettinicchio5Alberto Vannelli6Luca Sorrentino7Luigi Battaglia8Maurizio Cosimelli9Tommaso A. Dragani10Manuela Gariboldi11Institute of Biomedical Technologies, National Research Council (ITB-CNR)Genetic Epidemiology and Pharmacogenomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei TumoriGenetic Epidemiology and Pharmacogenomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei TumoriInstitute of Biomedical Technologies, National Research Council (ITB-CNR)Genetic Epidemiology and Pharmacogenomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei TumoriGenetic Epidemiology and Pharmacogenomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei TumoriDepartment of Surgery, Valduce HospitalColorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale dei TumoriColorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale dei TumoriColorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale dei TumoriGenetic Epidemiology and Pharmacogenomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei TumoriGenetic Epidemiology and Pharmacogenomics Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei TumoriAbstract The risk of colorectal cancer (CRC) depends on environmental and genetic factors. Among environmental factors, an imbalance in the gut microbiota can increase CRC risk. Also, microbiota is influenced by host genetics. However, it is not known if germline variants influence CRC development by modulating microbiota composition. We investigated germline variants associated with the abundance of bacterial populations in the normal (non-involved) colorectal mucosa of 93 CRC patients and evaluated their possible role in disease. Using a multivariable linear regression, we assessed the association between germline variants identified by genome wide genotyping and bacteria abundances determined by 16S rRNA gene sequencing. We identified 37 germline variants associated with the abundance of the genera Bacteroides, Ruminococcus, Akkermansia, Faecalibacterium and Gemmiger and with alpha diversity. These variants are correlated with the expression of 58 genes involved in inflammatory responses, cell adhesion, apoptosis and barrier integrity. Genes and bacteria appear to be involved in the same processes. In fact, expression of the pro-inflammatory genes GAL, GSDMD and LY6H was correlated with the abundance of Bacteroides, which has pro-inflammatory properties; abundance of the anti-inflammatory genus Faecalibacterium correlated with expression of KAZN, with barrier-enhancing functions. Both the microbiota composition and local inflammation are regulated, at least partially, by the same germline variants. These variants may regulate the microenvironment in which bacteria grow and predispose to the development of cancer. Identification of these variants is the first step to identifying higher-risk individuals and proposing tailored preventive treatments that increase beneficial bacterial populations.https://doi.org/10.1038/s41598-022-15230-6 |
| spellingShingle | Francesca Colombo Oscar Illescas Sara Noci Francesca Minnai Giulia Pintarelli Angela Pettinicchio Alberto Vannelli Luca Sorrentino Luigi Battaglia Maurizio Cosimelli Tommaso A. Dragani Manuela Gariboldi Gut microbiota composition in colorectal cancer patients is genetically regulated Scientific Reports |
| title | Gut microbiota composition in colorectal cancer patients is genetically regulated |
| title_full | Gut microbiota composition in colorectal cancer patients is genetically regulated |
| title_fullStr | Gut microbiota composition in colorectal cancer patients is genetically regulated |
| title_full_unstemmed | Gut microbiota composition in colorectal cancer patients is genetically regulated |
| title_short | Gut microbiota composition in colorectal cancer patients is genetically regulated |
| title_sort | gut microbiota composition in colorectal cancer patients is genetically regulated |
| url | https://doi.org/10.1038/s41598-022-15230-6 |
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