Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers
- 2.4k Downloads
Epidemiological studies demonstrate a link between gastrointestinal cancers and environmental factors such as diet. It has been suggested that environmental cancer risk is determined by the interaction between diet and microbes. Thus, the purpose of this study was to examine the hypothesis that microbiota composition during colorectal cancer (CRC) progression might differ depending on the stage of the disease.
A total of 28 age-matched and sex-matched subjects, seven with CRC adenocarcinoma, 11 with tubular adenomas and ten healthy subjects with intact colon, were included into the study. Microbiomes from mucosal and fecal samples were analyzed with 16S ribosomal RNA gene pyrosequencing, together with quantitative PCR of specific bacteria and archaea.
The principal coordinates analysis clearly separated healthy tissue samples from polyps and tumors, supporting the presence of specific bacterial consortia that are associated with affected sites and that can serve as potential biomarkers of CRC progression. A higher presence of Fusobacterium nucleatum and Enterobacteriaceae was found by qPCR in samples from CRC compared to healthy controls. We observed a correlation between CRC process development and levels of Methanobacteriales (R = 0.537, P = 0.007) and Methanobrevibacterium (R = 0.574, P = 0.03) in fecal samples.
Differences in microbial and archaeal composition between mucosal samples from healthy and disease tissues were observed in tubular adenoma and adenocarcinoma. In addition, microbiota from mucosal samples represented the underlying dysbiosis, whereas fecal samples seem not to be appropriate to detect shifts in microbial composition. CRC risk is influenced by microbial composition, showing differences according to disease progression step and tumor severity.
KeywordsColorectal cancer (CRC) Adenoma Adenocarcinoma Microbiota Bacteria Archaea Feces Mucosal tissue
EntreChem S.L. also acknowledges funding from FICYT (project IE-09-314).
Conflict of interest
The authors declare that they have no conflict of interest.
- 6.O’Keefe SJ, Chung D, Mahmoud N, Sepulveda AR, Manafe M, et al. Why do African Americans get more colon cancer than Native Africans? J Nutr. 2007;137:S75–82.Google Scholar
- 9.Giardiello FM, Brensinger JD, Petersen GM. AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology. 2001;21:198–213.Google Scholar
- 35.Balamurugan R, Rajendiran E, George S, Samuel GV, Ramakrishna BS. Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer. J Gastroenterol Hepatol. 2008;23(8 Pt 1):1298–303.PubMedCrossRefGoogle Scholar
- 47.Lyra A, Lahtinen S, Ouwehand AC. Gastrointestinal benefits of probiotics: clinical evidence. In: Salminen S, von Wright A, Lahtinen S, Ouwehand A, editors. Lactic acid bacteria: microbiological and functional aspects. 4th ed. Boca Raton: CRC Press; 2012. p. 509–23.Google Scholar
- 53.Million M, Angelakis E, Maraninchi M, Henry M, Giorgi R, Valero R, et al. Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. Int J Obes (Lond). 2013;37(11):1460–6.PubMedCentralCrossRefGoogle Scholar