Composition and Diversity Differences between Colon Microbiome of Colorectal Cancer Patients and Healthy Individuals by Age

Document Type : Original Article


1 Ph.D. Candidate in Molecular Genenetics, Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran

2 Professor, Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran

3 Assistant Professor, Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran

4 4Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran


Colorectal cancer (CRC) is the third cause of cancer death globally. New evidence suggests that colorectal microbiome dysbiosis may be involved in the cause and development of CRC. This study aimed to investigate the differences in bacterial composition and diversity between CRC samples and healthy individuals (HC) based on age through high-throughput 16S rRNA sequences. Biopsy samples were obtained from 17 CRC patients and 13 healthy controls (HC). We analyzed the colon microbiome composition and diversity by alpha and beta diversity. The results showed that colon microbial diversity was significantly higher in the CRC-32-50 and CRC-50-75 groups than in the healthy controls. Still, on the other hand, the diversity of group HC-32-50 was lower than all other groups. Prevotella, Faecalibacterium, Fusobacterium, and Akkermansia were overrepresented in the CRC-32-50, while Bacteroides were in the HC-32-50 group. Our results showed that the diversity and composition of the two groups, HC-32-50 and CRC-32-50, were significantly different. These findings suggest that dysbiosis is more common in CRC patients under the age of 50 than in those over 50. Further studies on the colon microbiome are needed to determine the diversity and composition of the colon microbiome in age-related colorectal cancer to complete our understanding of the impact of the microbiome on the progression of colon cancer.


Main Subjects

Allali, I., Boukhatem, N., Bouguenouch, L., Hardi, H., Boudouaya, H. A., Cadenas, M. B., Ouldim, K., Amzazi, S., Azcarate-Peril, M. A., & Ghazal, H. (2018). Gut microbiome of Moroccan colorectal cancer patients. Medical microbiology and immunology, 207(3), 211-225.
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 68(6), 394-424.
Edgar, R. C. (2010). Search and clustering orders of magnitude faster than BLAST. Bioinformatics, 26(19), 2460-2461.
Feng, Q., Liang, S., Jia, H., Stadlmayr, A., Tang, L., Lan, Z., Zhang, D., Xia, H., Xu, X., & Jie, Z. (2015). Gut microbiome development along the colorectal adenoma–carcinoma sequence. Nature communications, 6(1), 1-13.
Flint, H. J., Scott, K. P., Louis, P., & Duncan, S. H. (2012). The role of the gut microbiota in nutrition and health. Nature reviews Gastroenterology & hepatology, 9(10), 577.
Gagnière, J., Raisch, J., Veziant, J., Barnich, N., Bonnet, R., Buc, E., Bringer, M.-A., Pezet, D., & Bonnet, M. (2016). Gut microbiota imbalance and colorectal cancer. World journal of gastroenterology, 22(2), 501. doi: 10.3748/wjg.v22.i2.501.
Gallimidi, A. B., Fischman, S., Revach, B., Bulvik, R., Maliutina, A., Rubinstein, A. M., Nussbaum, G., & Elkin, M. (2015). Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model. Oncotarget, 6(26), 22613. doi: 10.18632/oncotarget.4209.
Gioula, G., Melidou, A., Siasios, P., Minti, F., & Malisiovas, N. (2018). 16S rRNA deep sequencing for the characterization of healthy human pharyngeal microbiome. Hippokratia, 22(1), 29.
Goodrich, J. K., Di Rienzi, S. C., Poole, A. C., Koren, O., Walters, W. A., Caporaso, J. G., Knight, R., & Ley, R. E. (2014). Conducting a microbiome study. Cell, 158(2), 250-262.
Hakansson, A., & Molin, G. (2011). Gut microbiota and inflammation. Nutrients, 3(6), 637-682.
Martin, A., Belcheva, A., Philpott, D. J., & Girardin, S. E. (2014). Multifaceted Role of the Intestinal Microbiota in Colon Cancer. Molecular cell.
Nardelli, C., Granata, I., D'Argenio, V., Tramontano, S., Compare, D., Guarracino, M. R., Nardone, G., Pilone, V., & Sacchetti, L. (2020). Characterization of the duodenal mucosal microbiome in obese adult subjects by 16S rRNA sequencing. Microorganisms, 8(4), 485.
Niccolai, E., Russo, E., Baldi, S., Ricci, F., Nannini, G., Pedone, M., Stingo, F. C., Taddei, A., Ringressi, M. N., & Bechi, P. (2020). Significant and conflicting correlation of IL-9 with Prevotella and Bacteroides in human colorectal cancer. Frontiers in immunology, 11.
Park, C. H., Han, D. S., Oh, Y.-H., Lee, A.-r., Lee, Y.-r., & Eun, C. S. (2016). Role of Fusobacteria in the serrated pathway of colorectal carcinogenesis. Scientific reports, 6(1), 1-8.
Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P., Alou, M. T., Daillère, R., Fluckiger, A., Messaoudene, M., Rauber, C., & Roberti, M. P. (2018). Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science, 359(6371), 91-97.
Rubinstein, M. R., Wang, X., Liu, W., Hao, Y., Cai, G., & Han, Y. W. (2013). Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell host & microbe, 14(2), 195-206.
Sobhani, I., Tap, J., Roudot-Thoraval, F., Roperch, J. P., Letulle, S., Langella, P., Corthier, G., Van Nhieu, J. T., & Furet, J. P. (2011). Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One, 6(1), e16393.
Tahara, T., Yamamoto, E., Suzuki, H., Maruyama, R., Chung, W., Garriga, J., Jelinek, J., Yamano, H.-o., Sugai, T., & An, B. (2014). Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer research, 74(5), 1311-1318. DOI: 10.1158/0008-5472.CAN-13-1865.         
Weinstock, G. M. (2012). Genomic approaches to studying the human microbiota. Nature, 489(7415), 250-256.
Wu, Y., Shi, L., Li, Q., Wu, J., Peng, W., Li, H., Chen, K., Ren, Y., & Fu, X. (2019). Microbiota diversity in human colorectal cancer tissues is associated with clinicopathological features. Nutrition and cancer, 71(2), 214-222.         
Zhou, Y., He, H., Xu, H., Li, Y., Li, Z., Du, Y., He, J., Zhou, Y., Wang, H., & Nie, Y. (2016). Association of oncogenic bacteria with colorectal cancer in South China. Oncotarget, 7(49), 80794. doi: 10.18632/oncotarget.13094.