Antibiotic-mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus-producing goblet cells and increased colorectal cancer progression

Cancer Med. 2018 May;7(5):2003-2012. doi: 10.1002/cam4.1460. Epub 2018 Apr 6.


Recent epidemiological evidence suggests that exposure to antibiotics in early-to-middle adulthood is associated with an increased risk of colorectal adenoma. However, mechanistic studies in established preclinical cancer to examine these claims are extremely limited. Therefore, we investigated the effect of long-term exposure of an antibiotic cocktail composed of Vancomycin, Neomycin, and Streptomycin, on tumor development and progression in the ApcMin/+ mouse, an established genetic model for familial adenomatous polyposis. Clinical pathologies related to tumor development as well as intestinal and colon tissue histopathology were studied at ages 8, 12, and 16 weeks of age, which correspond to the approximate ages of development of neoplasia, gut inflammation with polyposis, and cancer progression, respectively, in this animal model. We show that the antibiotics significantly increase the severity of clinical symptoms, including effects on intestinal histology and goblet cell numbers. In addition, they promote small intestinal polyposis. Finally, metagenomic analysis of fecal samples demonstrated that antibiotic exposure is associated with a significant but nonuniform depletion of the animal's natural gut flora. Overall, these findings support the premise that long-term antibiotic exposure mediates the selected depletion of gut microbial communities and the concomitant thinning of the protective mucus layer, resulting in an increase in tumor development.

Keywords: Antibiotics; Colorectal cancer; Goblet cells; Microbiome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / microbiology*
  • Adenomatous Polyposis Coli / pathology*
  • Adenomatous Polyposis Coli Protein / genetics
  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacology*
  • Colon / pathology
  • Disease Models, Animal
  • Disease Progression
  • Gastrointestinal Microbiome / drug effects*
  • Goblet Cells / cytology*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neomycin / adverse effects
  • Neomycin / pharmacology
  • Streptomycin / adverse effects
  • Streptomycin / pharmacology
  • Vancomycin / adverse effects
  • Vancomycin / pharmacology


  • Adenomatous Polyposis Coli Protein
  • Anti-Bacterial Agents
  • adenomatous polyposis coli protein, mouse
  • Vancomycin
  • Neomycin
  • Streptomycin