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Antibiotic-mediated bacteriome depletion in Apcmice is associated with reduction in mucus-producing goblet cells and increased colorectal cancer progression.

Antibiotic-mediated bacteriome depletion in Apcmice is associated with reduction in mucus-producing goblet cells and increased colorectal cancer progression.
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Kaur K, Saxena A, Debnath I, O'Brien JL, Ajami NJ, Auchtung TA, Petrosino JF, Sougiannis AJ, Depaep S, Chumanevich A, Gummadidala PM, Omebeyinje MH, Banerjee S, Chatzistamou I, Chakraborty P, Fayad R, Berger FG, Carson JA, Chanda A,


Kaur K, Saxena A, Debnath I, O'Brien JL, Ajami NJ, Auchtung TA, Petrosino JF, Sougiannis AJ, Depaep S, Chumanevich A, Gummadidala PM, Omebeyinje MH, Banerjee S, Chatzistamou I, Chakraborty P, Fayad R, Berger FG, Carson JA, Chanda A, (click to view)

Kaur K, Saxena A, Debnath I, O'Brien JL, Ajami NJ, Auchtung TA, Petrosino JF, Sougiannis AJ, Depaep S, Chumanevich A, Gummadidala PM, Omebeyinje MH, Banerjee S, Chatzistamou I, Chakraborty P, Fayad R, Berger FG, Carson JA, Chanda A,

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Cancer medicine 2018 04 06() doi 10.1002/cam4.1460

Abstract

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 Apcmouse, 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.

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