Fusobacterium Is Associated with Colorectal Adenomas

PLOS ONE, Dec 2019

The human gut microbiota is increasingly recognized as a player in colorectal cancer (CRC). While particular imbalances in the gut microbiota have been linked to colorectal adenomas and cancer, no specific bacterium has been identified as a risk factor. Recent studies have reported a high abundance of Fusobacterium in CRC subjects compared to normal subjects, but this observation has not been reported for adenomas, CRC precursors. We assessed the abundance of Fusobacterium species in the normal rectal mucosa of subjects with (n = 48) and without adenomas (n = 67). We also confirmed previous reports on Fusobacterium and CRC in 10 CRC tumor tissues and 9 matching normal tissues by pyrosequencing. We extracted DNA from rectal mucosal biopsies and measured bacterial levels by quantitative PCR of the 16S ribosomal RNA gene. Local cytokine gene expression was also determined in mucosal biopsies from adenoma cases and controls by quantitative PCR. The mean log abundance of Fusobacterium or cytokine gene expression between cases and controls was compared by t-test. Logistic regression was used to compare tertiles of Fusobacterium abundance. Adenoma subjects had a significantly higher abundance of Fusobacterium species compared to controls (p = 0.01). Compared to the lowest tertile, subjects with high abundance of Fusobacterium were significantly more likely to have adenomas (OR 3.66, 95% CI 1.37–9.74, p-trend 0.005). Cases but not controls had a significant positive correlation between local cytokine gene expression and Fusobacterium abundance. Among cases, the correlation for local TNF-α and Fusobacterium was r = 0.33, p = 0.06 while it was 0.44, p = 0.01 for Fusobacterium and IL-10. These results support a link between the abundance of Fusobacterium in colonic mucosa and adenomas and suggest a possible role for mucosal inflammation in this process.

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Fusobacterium Is Associated with Colorectal Adenomas

Citation: McCoy AN, Arau jo-Perez F, Azcarate-Peril A, Yeh JJ, Sandler RS, et al. ( Fusobacterium Is Associated with Colorectal Adenomas Amber N. McCoy 0 Fe lix Arau jo-Pe rez 0 Andrea Azca rate-Peril 0 Jen Jen Yeh 0 Robert S. Sandler 0 Temitope O. Keku 0 Ajay Goel, Baylor University Medical Center, United States of America 0 1 Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 2 Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 3 Microbiome Core Facility, Center for Gastrointestinal Biology and Disease and Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 4 Departments of Surgery and Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina , United States of America The human gut microbiota is increasingly recognized as a player in colorectal cancer (CRC). While particular imbalances in the gut microbiota have been linked to colorectal adenomas and cancer, no specific bacterium has been identified as a risk factor. Recent studies have reported a high abundance of Fusobacterium in CRC subjects compared to normal subjects, but this observation has not been reported for adenomas, CRC precursors. We assessed the abundance of Fusobacterium species in the normal rectal mucosa of subjects with (n = 48) and without adenomas (n = 67). We also confirmed previous reports on Fusobacterium and CRC in 10 CRC tumor tissues and 9 matching normal tissues by pyrosequencing. We extracted DNA from rectal mucosal biopsies and measured bacterial levels by quantitative PCR of the 16S ribosomal RNA gene. Local cytokine gene expression was also determined in mucosal biopsies from adenoma cases and controls by quantitative PCR. The mean log abundance of Fusobacterium or cytokine gene expression between cases and controls was compared by t-test. Logistic regression was used to compare tertiles of Fusobacterium abundance. Adenoma subjects had a significantly higher abundance of Fusobacterium species compared to controls (p = 0.01). Compared to the lowest tertile, subjects with high abundance of Fusobacterium were significantly more likely to have adenomas (OR 3.66, 95% CI 1.37-9.74, p-trend 0.005). Cases but not controls had a significant positive correlation between local cytokine gene expression and Fusobacterium abundance. Among cases, the correlation for local TNF-a and Fusobacterium was r = 0.33, p = 0.06 while it was 0.44, p = 0.01 for Fusobacterium and IL-10. These results support a link between the abundance of Fusobacterium in colonic mucosa and adenomas and suggest a possible role for mucosal inflammation in this process. - Funding: This work was supported by grants from the National Institutes of Health NIH R01 CA04468, R01 CA136887, P50 CA106991 and P30 DK034987. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. The human intestinal microbiota inhabits a complex and diverse environment populated by hundreds of different bacterial species. The number of bacterial cells in the gut exceeds all other eukaryotic cells in the human body by a factor of 10 [1,2]. These bacteria are regulated in the gut by the mucosal immune system, which is made up of a complex network of functions and immune responses aimed at maintaining a cooperative system between the intestinal microbiota and the host [1]. In a healthy gut these bacteria maintain homeostasis with the host. However, when an imbalance, or bacterial dysbiosis, occurs in the gut, the host may experience inflammation and a loss of barrier function [3,4]. Bacterial dysbioses have been linked to several diseases including ulcerative colitis, Crohns disease [57] and colorectal cancer (CRC) [8,9]. Current research is focused on identifying key players in this imbalance as well as their specific contribution to colorectal carcinogenesis. No single bacterial species has been identified as a risk factor for CRC, but recent studies report an increase in the abundance of Fusobacterium in human colorectal tumors compared to controls [8,10,11]. These studies suggest that Fusobacterium may be associated with the later stages of CRC, but it is unknown if they play a role in the early stages of colorectal carcinogenesis. While the causes of colorectal cancer are not fully known, it is becoming increasingly clear that the gut microbiota provide an important contribution [12]. We evaluated whether Fusobacterium nucleatum in normal rectal mucosal biopsies was associated with colorectal adenomas. We also examined a potential association between local inflam (...truncated)


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Amber N. McCoy, Félix Araújo-Pérez, Andrea Azcárate-Peril, Jen Jen Yeh, Robert S. Sandler, Temitope O. Keku. Fusobacterium Is Associated with Colorectal Adenomas, PLOS ONE, 2013, Volume 8, Issue 1, DOI: 10.1371/journal.pone.0053653