Intestinal bacteria are necessary for doxorubicin-induced intestinal damage but not for doxorubicin-induced apoptosis

Rigby, Rachael Jane and Carr, Jacquelyn and Orgel, Kelly and King, Stephanie L. and Lund, P. Kay and Dekaney, Christopher M. (2016) Intestinal bacteria are necessary for doxorubicin-induced intestinal damage but not for doxorubicin-induced apoptosis. Gut Microbes, 7 (5). pp. 414-423. ISSN 1949-0984

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Abstract

Doxorubicin (DOXO) induces significant, but transient, increases in apoptosis in the stem cell zone of the jejunum, followed by mucosal damage involving a decrease in crypt proliferation, crypt number, and villus height. The gastrointestinal tract is home to a vast population of commensal bacteria and numerous studies have demonstrated a symbiotic relationship between intestinal bacteria and intestinal epithelial cells (IEC) in maintaining homeostatic functions of the intestine. However, whether enteric bacteria play a role in DOXO-induced damage is not well understood. We hypothesized that enteric bacteria are necessary for induction of apoptosis and damage associated with DOXO treatment. Conventionally raised (CONV) and germ free (GF) mice were given a single injection of DOXO, and intestinal tissue was collected at 6, 72, and 120 h after treatment and from no treatment (0 h) controls. Histology and morphometric analyses quantified apoptosis, mitosis, crypt depth, villus height, and crypt density. Immunostaining for muc2 and lysozyme evaluated Paneth cells, goblet cells or dual stained intermediate cells. DOXO administration induced significant increases in apoptosis in jejunal epithelium regardless of the presence of enteric bacteria; however, the resulting injury, as demonstrated by statistically significant changes in crypt depth, crypt number, and proliferative cell number, was dependent upon the presence of enteric bacteria. Furthermore, we observed expansion of Paneth and goblet cells and presence of intermediate cells only in CONV and not GF mice. These findings provide evidence that manipulation and/or depletion of the enteric microbiota may have clinical significance in limiting chemotherapy-induced mucositis.

Item Type:
Journal Article
Journal or Publication Title:
Gut Microbes
Additional Information:
This is an Accepted Manuscript of an article published by Taylor & Francis in Gut Microbes on 26/07/2016, available online: http://www.tandfonline.com/doi/full/10.1080/19490976.2016.1215806
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2400/2404
Subjects:
ID Code:
80625
Deposited By:
Deposited On:
14 Sep 2016 15:38
Refereed?:
Yes
Published?:
Published
Last Modified:
09 Aug 2020 04:30