Differences Between the Intestinal Lumen Microbiota of Aberrant Crypt Foci (ACF)-Bearing and Non-bearing Rats



Multiple factors including host–microbiota interaction could contribute to the conversion of healthy mucosa to sporadic precancerous lesions. An imbalance of the gut microbiota may be a cause or consequence of this process.


The goal was to investigate and analyze the composition of gut microbiota during the genesis of precancerous lesions of colorectal cancer.


To analyze the composition of gut microbiota in the genesis of precancerous lesions, a rat model of 1, 2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) was established. The feces of these rats and healthy rats were collected for 16S rRNA sequencing.


The diversity and density of the rat intestinal microbiota were significantly different between ACF-bearing and non-bearing group. ACF were induced in rats treated with DMH and showed increased expression of the inflammatory cytokines IL-6, IL-8, and TNF-α. Firmicutes was the most predominant phylum in both ACF-bearing and non-bearing group, followed by Bacteroidetes. Interestingly, although the density of Bacteroidetes decreased from the fifth week to the 17th week in both groups, it was significantly reduced in ACF-bearing group at the 13th week (P < 0.01). At the genus level, no significant difference was observed in the most predominant genus, Lactobacillus. Instead, Bacteroides and Prevotella were significantly less abundant (P < 0.01), while Akkermansia was significantly more abundant (P < 0.05) in ACF-bearing group at the 13th week.


Imbalance of the intestinal microbiota existed between ACF-bearing and non-bearing rats, which could be used as biomarker to predict the genesis of precancerous lesions in the gut.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Yang L, Pei Z. Bacteria, inflammation, and colon cancer. World J Gastroenterol. 2006;12:6741–6746.

    CAS  Article  Google Scholar 

  2. 2.

    Rowland IR. The role of the gastrointestinal microbiota in colorectal cancer. Curr Pharm Des. 2009;15:1524–1527.

    CAS  Article  Google Scholar 

  3. 3.

    Ahn J, Sinha R, Pei Z, et al. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst. 2013;105:1907–1911.

    CAS  Article  Google Scholar 

  4. 4.

    Wong SH, Kwong TNY, Chow TC, et al. Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia. Gut. 2017;66:1441–1448.

    Article  Google Scholar 

  5. 5.

    Wei H, Dong L, Wang T, et al. Structural shifts of gut microbiota as surrogate endpoints for monitoring host health changes induced by carcinogen exposure. FEMS Microbiol Ecol. 2010;73:577–586.

    CAS  PubMed  Google Scholar 

  6. 6.

    Liang X, Li H, Tian G, et al. Dynamic microbe and molecule networks in a mouse model of colitis-associated colorectal cancer. Sci Rep. 2014;4:4985.

    CAS  Article  Google Scholar 

  7. 7.

    Sun T, Liu S, Zhou Y, et al. Evolutionary biologic changes of gut microbiota in an ‘adenoma-carcinoma sequence’ mouse colorectal cancer model induced by 1, 2-Dimethylhydrazine. Oncotarget. 2017;8:444.

    PubMed  Google Scholar 

  8. 8.

    Mori H, Yamada Y, Kuno T, et al. Aberrant crypt foci and beta-catenin accumulated crypts; significance and roles for colorectal carcinogenesis. Mutat Res. 2004;566:191–208.

    CAS  Article  Google Scholar 

  9. 9.

    Fadrosh DW, Ma B, Gajer P, et al. An improved dual-indexing approach for multiplexed 16S rRNA gene sequencing on the Illumina MiSeq platform. Microbiome. 2014;2:6.

    Article  Google Scholar 

  10. 10.

    Roncucci L, Pedroni M, Vaccina F, et al. Aberrant crypt foci in colorectal carcinogenesis. Cell and crypt dynamics. Cell Proliferat. 2000;33:1–18.

    CAS  Article  Google Scholar 

  11. 11.

    Padidar S, Farquharson AJ, Williams LM, et al. High-fat diet alters gene expression in the liver and colon: links to increased development of aberrant crypt foci. Dig Dis Sci. 2012;57:1866.

    CAS  Article  Google Scholar 

  12. 12.

    Prasad VG, Kawade S, Jayashree BS, et al. Iminoflavones combat 1,2-dimethyl hydrazine-induced aberrant crypt foci development in colon cancer. Biomed Res Int. 2014;2014:1–7.

    Google Scholar 

  13. 13.

    Abdulamir AS, Hafidh RR, Bakar FA. Molecular detection, quantification, and isolation of Streptococcus gallolyticus, bacteria colonizing colorectal tumors: inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8. Mol Cancer. 2010;9:1–18.

    Article  Google Scholar 

  14. 14.

    Likhachev A, Anisimov V, Parvanova L, et al. Effect of exogenous beta-glucuronidase on the carcinogenicity of 1,2-dimethylhydrazine in rats: evidence that carcinogenic intermediates form conjugates and act through their subsequent enzymatic release. Carcinogenesis. 1985;6:679–681.

    CAS  Article  Google Scholar 

  15. 15.

    de Lima RO, Bazo AP, Said RA, et al. Modifying effect of propolis on dimethylhydrazine-induced DNA damage but not colonic aberrant crypt foci in rats. Environ Mol Mutagen. 2005;45:8–16.

    Article  Google Scholar 

  16. 16.

    Lunz W, Peluzio MC, Dias CM, et al. Long-term aerobic swimming training by rats reduces the number of aberrant crypt foci in 1,2-dimethylhydrazine-induced colon cancer. Braz J Med Biol Res. 2008;41:1000–1004.

    CAS  Article  Google Scholar 

  17. 17.

    Hu Y, Leu RKL, Christophersen CT, et al. Manipulation of the gut microbiota using resistant starch is associated with protection against colitis-associated colorectal cancer in rats. Carcinogenesis. 2016;37:366.

    CAS  Article  Google Scholar 

  18. 18.

    Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–1031.

    Article  Google Scholar 

  19. 19.

    Frank DN, St Amand AL, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA. 2007;104:13780–13785.

    CAS  Article  Google Scholar 

  20. 20.

    Zhu Q, Jin Z, Wu W, et al. Analysis of the intestinal lumen microbiota in an animal model of colorectal cancer. PLoS ONE. 2014;9:e90849.

    Article  Google Scholar 

  21. 21.

    Sobhani I, Tap J, Roudot-Thoraval F, et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS ONE. 2011;6:e16393.

    CAS  Article  Google Scholar 

  22. 22.

    Sears CL, Islam S, Saha A, et al. Association of enterotoxigenic Bacteroides fragilis infection with inflammatory diarrhea. Clin Infect Dis. 2008;47:797–803.

    CAS  Article  Google Scholar 

  23. 23.

    Zhang M, Fan X, Fang B, et al. Effects of Lactobacillus salivarius Ren on cancer prevention and intestinal microbiota in 1,2-dimethylhydrazine-induced rat model. J Microbiol.. 2015;53:398–405.

    Article  Google Scholar 

  24. 24.

    Baxter NT, Zackular JP, Chen GY, et al. Structure of the gut microbiome following colonization with human feces determines colonic tumor burden. Microbiome. 2014;2:20.

    Article  Google Scholar 

  25. 25.

    Weir TL, Manter DK, Sheflin AM, et al. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS ONE. 2013;8:e70803.

    CAS  Article  Google Scholar 

  26. 26.

    Thomas LV, Ockhuizen T, Suzuki K. Exploring the influence of the gut microbiota and probiotics on health: a symposium report. Br J Nutr. 2014;112:S1–18.

    CAS  Article  Google Scholar 

  27. 27.

    Byrd JC, Bresalier RS. Mucins and mucin binding proteins in colorectal cancer: colorectal cancer. Cancer Metastasis Rev. 2004;23:77–99.

    CAS  Article  Google Scholar 

Download references


This Project is supported by the “Project of special Fund for science and technology of Sichuan” (Number: LY-55).

Author information




XLX and HAL conceived the project. TYH, TX, RPY, and YL performed the experiments. WBL and XLX analyzed the data and wrote/edited the manuscript.

Corresponding author

Correspondence to Hanan Long.

Ethics declarations

Conflict of interest

Authors confirm that there is no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplemental Table 1

Operational taxonomic units (OTUs) produced bysequencing16S RNA genes of rats. NGS, non-bearing group stool; AGS, ACF-bearing group stool (XLSX 4108 kb)

Supplemental Table 2

Data of relative contributions of dominant phyla and genera in the intestinal lumen microbiota. NGS, non-bearing group stool; AGS, ACF-bearing group stool. “Others” represents the unclassified bacteria (XLSX 36 kb)

Supplemental Table 3

Relative abundance, median, and range of the predominant genera in the gut microbiota of ACF-bearing and non-bearing group.“Others” represents the unclassified bacteria (DOCX 24 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Xiao, X., Long, W., Huang, T. et al. Differences Between the Intestinal Lumen Microbiota of Aberrant Crypt Foci (ACF)-Bearing and Non-bearing Rats. Dig Dis Sci 63, 2923–2929 (2018). https://doi.org/10.1007/s10620-018-5180-7

Download citation


  • Aberrant crypt foci (ACF)
  • Intestinal microbiota
  • Rat model
  • Precancerous lesions