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

Kamaljeet Kaur, Arpit Saxena, Irina Debnath, Jacqueline L. O'Brien, Nadim J. Ajami, Thomas A. Auchtung, Joseph F. Petrosino, Alexander Jacques Sougiannis, Sarah Depaep, Alexander Chumanevich, Phani M. Gummadidala, Mayomi H. Omebeyinje, Sourav Banerjee, Ioulia Chatzistamou, Paramita Chakraborty, Raja Fayad, Franklin G. Berger, James Carson, Anindya Chanda

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)2003-2012
Number of pages10
JournalCancer Medicine
Volume7
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Goblet Cells
Mucus
Colorectal Neoplasms
Anti-Bacterial Agents
Neoplasms
Intestinal Polyposis
Metagenomics
Adenomatous Polyposis Coli
Clinical Pathology
Neomycin
Genetic Models
Streptomycin
Vancomycin
Adenoma
Histology
Colon
Animal Models
Cell Count
Inflammation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Antibiotic-mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus-producing goblet cells and increased colorectal cancer progression. / Kaur, Kamaljeet; Saxena, Arpit; Debnath, Irina; O'Brien, Jacqueline L.; Ajami, Nadim J.; Auchtung, Thomas A.; Petrosino, Joseph F.; Sougiannis, Alexander Jacques; Depaep, Sarah; Chumanevich, Alexander; Gummadidala, Phani M.; Omebeyinje, Mayomi H.; Banerjee, Sourav; Chatzistamou, Ioulia; Chakraborty, Paramita; Fayad, Raja; Berger, Franklin G.; Carson, James; Chanda, Anindya.

In: Cancer Medicine, Vol. 7, No. 5, 01.05.2018, p. 2003-2012.

Research output: Contribution to journalArticle

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, J & Chanda, A 2018, 'Antibiotic-mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus-producing goblet cells and increased colorectal cancer progression', Cancer Medicine, vol. 7, no. 5, pp. 2003-2012. https://doi.org/10.1002/cam4.1460
Kaur, Kamaljeet ; Saxena, Arpit ; Debnath, Irina ; O'Brien, Jacqueline L. ; Ajami, Nadim J. ; Auchtung, Thomas A. ; Petrosino, Joseph F. ; Sougiannis, Alexander Jacques ; Depaep, Sarah ; Chumanevich, Alexander ; Gummadidala, Phani M. ; Omebeyinje, Mayomi H. ; Banerjee, Sourav ; Chatzistamou, Ioulia ; Chakraborty, Paramita ; Fayad, Raja ; Berger, Franklin G. ; Carson, James ; Chanda, Anindya. / Antibiotic-mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus-producing goblet cells and increased colorectal cancer progression. In: Cancer Medicine. 2018 ; Vol. 7, No. 5. pp. 2003-2012.
@article{f805e1a7ed534209a2b0d1cd3b4e1237,
title = "Antibiotic-mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus-producing goblet cells and increased colorectal cancer progression",
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 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.",
author = "Kamaljeet Kaur and Arpit Saxena and Irina Debnath and O'Brien, {Jacqueline L.} and Ajami, {Nadim J.} and Auchtung, {Thomas A.} and Petrosino, {Joseph F.} and Sougiannis, {Alexander Jacques} and Sarah Depaep and Alexander Chumanevich and Gummadidala, {Phani M.} and Omebeyinje, {Mayomi H.} and Sourav Banerjee and Ioulia Chatzistamou and Paramita Chakraborty and Raja Fayad and Berger, {Franklin G.} and James Carson and Anindya Chanda",
year = "2018",
month = "5",
day = "1",
doi = "10.1002/cam4.1460",
language = "English (US)",
volume = "7",
pages = "2003--2012",
journal = "Cancer Medicine",
issn = "2045-7634",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

TY - JOUR

T1 - Antibiotic-mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus-producing goblet cells and increased colorectal cancer progression

AU - Kaur, Kamaljeet

AU - Saxena, Arpit

AU - Debnath, Irina

AU - O'Brien, Jacqueline L.

AU - Ajami, Nadim J.

AU - Auchtung, Thomas A.

AU - Petrosino, Joseph F.

AU - Sougiannis, Alexander Jacques

AU - Depaep, Sarah

AU - Chumanevich, Alexander

AU - Gummadidala, Phani M.

AU - Omebeyinje, Mayomi H.

AU - Banerjee, Sourav

AU - Chatzistamou, Ioulia

AU - Chakraborty, Paramita

AU - Fayad, Raja

AU - Berger, Franklin G.

AU - Carson, James

AU - Chanda, Anindya

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85044952219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044952219&partnerID=8YFLogxK

U2 - 10.1002/cam4.1460

DO - 10.1002/cam4.1460

M3 - Article

VL - 7

SP - 2003

EP - 2012

JO - Cancer Medicine

JF - Cancer Medicine

SN - 2045-7634

IS - 5

ER -