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Distinct Colon Mucosa Microbiomes associated with Tubular Adenomas and Serrated Polyps

View ORCID ProfileJulio Avelar-Barragan, Lauren DeDecker, Zachary Lu, Bretton Coppedge, View ORCID ProfileWilliam E. Karnes, View ORCID ProfileKatrine L. Whiteson
doi: https://doi.org/10.1101/2021.07.20.453135
Julio Avelar-Barragan
*School of Biological Sciences, University of California, Irvine
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  • For correspondence: javelarb@uci.edu
Lauren DeDecker
**School of Medicine, University of California, Irvine
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Zachary Lu
**School of Medicine, University of California, Irvine
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Bretton Coppedge
*School of Biological Sciences, University of California, Irvine
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William E. Karnes
**School of Medicine, University of California, Irvine
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Katrine L. Whiteson
*School of Biological Sciences, University of California, Irvine
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Abstract

Background 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 unclear. 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.

Results We discovered significant differences between colon mucosa and fecal samples, explaining 14% of the variation observed in the microbiome. Multiple mucosal samples were collected from each individual to investigate the gut microbiome for differences between polyp and healthy intestinal tissue, but no such differences were found. Colon mucosa sampling revealed that the microbiomes of individuals with tubular adenomas and serrated polyps were significantly different from each other and polyp-free individuals, explaining 2-10% of the variance in the microbiome. Further analysis revealed differential abundances of Eggerthella lenta, Clostridium scindens, and three microbial genes across tubular adenoma, serrated polyp, and polyp-free cases.

Conclusion By directly sampling the colon mucosa and distinguishing between the different developmental pathways of colorectal cancer, this study helps characterize potential mechanistic targets and diagnostic biomarkers 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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 21, 2021.
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Distinct Colon Mucosa Microbiomes associated with Tubular Adenomas and Serrated Polyps
Julio Avelar-Barragan, Lauren DeDecker, Zachary Lu, Bretton Coppedge, William E. Karnes, Katrine L. Whiteson
bioRxiv 2021.07.20.453135; doi: https://doi.org/10.1101/2021.07.20.453135
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Distinct Colon Mucosa Microbiomes associated with Tubular Adenomas and Serrated Polyps
Julio Avelar-Barragan, Lauren DeDecker, Zachary Lu, Bretton Coppedge, William E. Karnes, Katrine L. Whiteson
bioRxiv 2021.07.20.453135; doi: https://doi.org/10.1101/2021.07.20.453135

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