Distinct colon mucosa microbiomes associated with tubular adenomas and serrated polyps
Abstract Colorectal cancer is the second most deadly and third most common cancer in the world. Its development is heterogenous, with multiple mechanisms of carcinogenesis. Two distinct mechanisms include the adenoma-carcinoma sequence and the serrated pathway. The gut microbiome has been identified...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-08-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-022-00328-6 |
| _version_ | 1798032495687499776 |
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| author | Julio Avelar-Barragan Lauren DeDecker Zachary N. Lu Bretton Coppedge William E. Karnes Katrine L. Whiteson |
| author_facet | Julio Avelar-Barragan Lauren DeDecker Zachary N. Lu Bretton Coppedge William E. Karnes Katrine L. Whiteson |
| author_sort | Julio Avelar-Barragan |
| collection | DOAJ |
| description | Abstract Colorectal cancer is the second most deadly and third most common cancer in the world. Its development is heterogenous, with multiple mechanisms of carcinogenesis. Two distinct mechanisms include the adenoma-carcinoma sequence and the serrated pathway. The gut microbiome has been identified as a key player in the adenoma-carcinoma sequence, but its role in serrated carcinogenesis is less clear. In this study, we characterized the gut microbiome of 140 polyp-free and polyp-bearing individuals using colon mucosa and fecal samples to determine if microbiome composition was associated with each of the two key pathways. We discovered significant differences between the microbiomes of colon mucosa and fecal samples, with sample type explaining 10–15% of the variation observed in the microbiome. Multiple mucosal brushings were collected from each individual to investigate whether the gut microbiome differed between polyp and healthy intestinal tissue, but no differences were found. Mucosal aspirate sampling revealed that the microbiomes of individuals with tubular adenomas and serrated polyps were significantly different from each other and polyp-free individuals, explaining 1–4% of the variance in the microbiome. Microbiome composition also enabled the accurate prediction of subject polyp types using Random Forest, which produced an area under curve values of 0.87–0.99. By directly sampling the colon mucosa and distinguishing between the different developmental pathways of colorectal cancer, our study helps characterize potential mechanistic targets for serrated carcinogenesis. This research also provides insight into multiple microbiome sampling strategies by assessing each method’s practicality and effect on microbial community composition. |
| first_indexed | 2024-04-11T20:13:47Z |
| format | Article |
| id | doaj.art-808dc42b8f4d4bbdadd4ddeeecb58db0 |
| institution | Directory Open Access Journal |
| issn | 2055-5008 |
| language | English |
| last_indexed | 2024-04-11T20:13:47Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj.art-808dc42b8f4d4bbdadd4ddeeecb58db02022-12-22T04:05:01ZengNature Portfolionpj Biofilms and Microbiomes2055-50082022-08-018111210.1038/s41522-022-00328-6Distinct colon mucosa microbiomes associated with tubular adenomas and serrated polypsJulio Avelar-Barragan0Lauren DeDecker1Zachary N. Lu2Bretton Coppedge3William E. Karnes4Katrine L. Whiteson5School of Biological Sciences, University of CaliforniaSchool of Medicine, University of CaliforniaSchool of Medicine, University of CaliforniaSchool of Biological Sciences, University of CaliforniaSchool of Medicine, University of CaliforniaSchool of Biological Sciences, University of CaliforniaAbstract Colorectal cancer is the second most deadly and third most common cancer in the world. Its development is heterogenous, with multiple mechanisms of carcinogenesis. Two distinct mechanisms include the adenoma-carcinoma sequence and the serrated pathway. The gut microbiome has been identified as a key player in the adenoma-carcinoma sequence, but its role in serrated carcinogenesis is less clear. In this study, we characterized the gut microbiome of 140 polyp-free and polyp-bearing individuals using colon mucosa and fecal samples to determine if microbiome composition was associated with each of the two key pathways. We discovered significant differences between the microbiomes of colon mucosa and fecal samples, with sample type explaining 10–15% of the variation observed in the microbiome. Multiple mucosal brushings were collected from each individual to investigate whether the gut microbiome differed between polyp and healthy intestinal tissue, but no differences were found. Mucosal aspirate sampling revealed that the microbiomes of individuals with tubular adenomas and serrated polyps were significantly different from each other and polyp-free individuals, explaining 1–4% of the variance in the microbiome. Microbiome composition also enabled the accurate prediction of subject polyp types using Random Forest, which produced an area under curve values of 0.87–0.99. By directly sampling the colon mucosa and distinguishing between the different developmental pathways of colorectal cancer, our study helps characterize potential mechanistic targets for serrated carcinogenesis. This research also provides insight into multiple microbiome sampling strategies by assessing each method’s practicality and effect on microbial community composition.https://doi.org/10.1038/s41522-022-00328-6 |
| spellingShingle | Julio Avelar-Barragan Lauren DeDecker Zachary N. Lu Bretton Coppedge William E. Karnes Katrine L. Whiteson Distinct colon mucosa microbiomes associated with tubular adenomas and serrated polyps npj Biofilms and Microbiomes |
| title | Distinct colon mucosa microbiomes associated with tubular adenomas and serrated polyps |
| title_full | Distinct colon mucosa microbiomes associated with tubular adenomas and serrated polyps |
| title_fullStr | Distinct colon mucosa microbiomes associated with tubular adenomas and serrated polyps |
| title_full_unstemmed | Distinct colon mucosa microbiomes associated with tubular adenomas and serrated polyps |
| title_short | Distinct colon mucosa microbiomes associated with tubular adenomas and serrated polyps |
| title_sort | distinct colon mucosa microbiomes associated with tubular adenomas and serrated polyps |
| url | https://doi.org/10.1038/s41522-022-00328-6 |
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