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 investig...
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| Format: | Article |
| Language: | English |
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Wiley
2018-05-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.1460 |
| _version_ | 1811154920458420224 |
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| author | 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 A. Carson Anindya Chanda |
| author_facet | 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 A. Carson Anindya Chanda |
| author_sort | Kamaljeet Kaur |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T04:25:20Z |
| format | Article |
| id | doaj.art-ac2cceb9552043269ae1f4d0e672dde8 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-10T04:25:20Z |
| publishDate | 2018-05-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj.art-ac2cceb9552043269ae1f4d0e672dde82023-03-10T15:42:22ZengWileyCancer Medicine2045-76342018-05-01752003201210.1002/cam4.1460Antibiotic‐mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus‐producing goblet cells and increased colorectal cancer progressionKamaljeet Kaur0Arpit Saxena1Irina Debnath2Jacqueline L. O'Brien3Nadim J. Ajami4Thomas A. Auchtung5Joseph F. Petrosino6Alexander‐Jacques Sougiannis7Sarah Depaep8Alexander Chumanevich9Phani M. Gummadidala10Mayomi H. Omebeyinje11Sourav Banerjee12Ioulia Chatzistamou13Paramita Chakraborty14Raja Fayad15Franklin G. Berger16James A. Carson17Anindya Chanda18Exercise Science, Arnold School of Public Health University of South Carolina Columbia South CarolinaExercise Science, Arnold School of Public Health University of South Carolina Columbia South CarolinaEnvironmental Health Sciences, Arnold School of Public Health University of South Carolina Columbia South CarolinaThe Alkek Center for Metagenomics and Microbiome Research Department of Molecular Virology and Microbiology Baylor College of Medicine Houston TexasThe Alkek Center for Metagenomics and Microbiome Research Department of Molecular Virology and Microbiology Baylor College of Medicine Houston TexasThe Alkek Center for Metagenomics and Microbiome Research Department of Molecular Virology and Microbiology Baylor College of Medicine Houston TexasThe Alkek Center for Metagenomics and Microbiome Research Department of Molecular Virology and Microbiology Baylor College of Medicine Houston TexasExercise Science, Arnold School of Public Health University of South Carolina Columbia South CarolinaExercise Science, Arnold School of Public Health University of South Carolina Columbia South CarolinaExercise Science, Arnold School of Public Health University of South Carolina Columbia South CarolinaEnvironmental Health Sciences, Arnold School of Public Health University of South Carolina Columbia South CarolinaEnvironmental Health Sciences, Arnold School of Public Health University of South Carolina Columbia South CarolinaMechanical Engineering University of South Carolina Columbia South CarolinaPathology, Microbiology& Immunology, School of Medicine University of South Carolina Columbia South CarolinaDepartment of Statistics University of South Carolina Columbia South CarolinaExercise Science, Arnold School of Public Health University of South Carolina Columbia South CarolinaCenter for Colon Cancer Research University of South Carolina Columbia South CarolinaExercise Science, Arnold School of Public Health University of South Carolina Columbia South CarolinaEnvironmental Health Sciences, Arnold School of Public Health University of South Carolina Columbia South CarolinaAbstract 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.https://doi.org/10.1002/cam4.1460AntibioticsColorectal cancerGoblet cellsMicrobiome |
| spellingShingle | 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 A. Carson Anindya Chanda Antibiotic‐mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus‐producing goblet cells and increased colorectal cancer progression Cancer Medicine Antibiotics Colorectal cancer Goblet cells Microbiome |
| title | Antibiotic‐mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus‐producing goblet cells and increased colorectal cancer progression |
| title_full | Antibiotic‐mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus‐producing goblet cells and increased colorectal cancer progression |
| title_fullStr | Antibiotic‐mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus‐producing goblet cells and increased colorectal cancer progression |
| title_full_unstemmed | Antibiotic‐mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus‐producing goblet cells and increased colorectal cancer progression |
| title_short | Antibiotic‐mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus‐producing goblet cells and increased colorectal cancer progression |
| title_sort | antibiotic mediated bacteriome depletion in apcmin mice is associated with reduction in mucus producing goblet cells and increased colorectal cancer progression |
| topic | Antibiotics Colorectal cancer Goblet cells Microbiome |
| url | https://doi.org/10.1002/cam4.1460 |
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