Open AccessAntibiotic‐mediated bacteriome depletion in Apc Min/+ mice is associated with reduction in mucus‐producing goblet cells and increased colorectal cancer progression
Author(s) -
Kaur Kamaljeet,
Saxena Arpit,
Debnath Irina,
O'Brien Jacqueline L.,
Ajami Nadim J.,
Auchtung Thomas A.,
Petrosino Joseph F.,
Sougiannis AlexanderJacques,
Depaep Sarah,
Chumanevich Alexander,
Gummadidala Phani M.,
Omebeyinje Mayomi H.,
Banerjee Sourav,
Chatzistamou Ioulia,
Chakraborty Paramita,
Fayad Raja,
Berger Franklin G.,
Carson James A.,
Chanda Anindya
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1460
Subject(s) - goblet cell , antibiotics , colorectal cancer , mucus , biology , gut flora , cancer , medicine , immunology , pathology , microbiology and biotechnology , epithelium , ecology
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 Apc Min/+ 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.