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Role of the Oral Microbiome in 5FU-I...

Luna, Melissa,

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Role of the Oral Microbiome in 5FU-Induced Oral Mucositis /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Role of the Oral Microbiome in 5FU-Induced Oral Mucositis // Melissa Luna.
Author:	Luna, Melissa,
Description:	1 electronic resource (55 pages)
Notes:	Source: Masters Abstracts International, Volume: 86-03.
Contained By:	Masters Abstracts International86-03.
Subject:	Dentistry. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31490012
ISBN:	9798384091196

Role of the Oral Microbiome in 5FU-Induced Oral Mucositis /
Luna, Melissa,

Role of the Oral Microbiome in 5FU-Induced Oral Mucositis /Melissa Luna. - 1 electronic resource (55 pages)

Source: Masters Abstracts International, Volume: 86-03.

Oral mucositis is a greatly debilitating, yet common complication of cancer chemotherapy. Despite its significance, the pathophysiology of oral mucositis is incompletely understood. Recent clinical studies show that oral microbiome dysbiosis occurs during chemotherapy and is associated with oral mucositis severity. While mucosal damage is a response to chemotherapy toxicity, whether a dysbiotic microbiome influences oral mucosal responses to chemotherapy is unknown. The aim of this study was to evaluate the effects of antibiotic-mediated oral microbiome ablation on oral mucositis utilizing a mouse model. 7-week-old mice received an antibiotic cocktail in drinking water for 7 days followed by 5-fluorouracil (5FU) intraperitoneal injections for 7 days with continued antibiotics. Control groups included mice that did not receive antibiotics prior to 5FU treatment, mice that received the 5FU vehicle (PBS) only and mice that received PBS plus antibiotics. Mice were euthanized on days 4 and 6 after commencing 5FU. Oral bacterial load was evaluated by plating on blood agar. In addition, tongue tissues were stained with toluidine-blue to detect macroscopic lesions. Tongue sections were then subjected to histological examination after hematoxylin and eosin staining and immunohistochemistry for the cell proliferation marker Ki67. Gene expression of selected targets was quantified via RT-qPCR.We observed an increased in oral bacterial load following administration of 5FU, and this change was inhibited by the use of antibiotics. Furthermore, lesions occupied significantly smaller areas of the tongue in mice that received antibiotic treatment. Antibiotics did not prevent the severe atrophy or decreased basal cell layer density of the epithelium caused by 5FU. Mice that received 5FU alone and those that were treated with both 5FU and antibiotics showed decreased Ki67 staining indicative of decreased basal cell proliferation compared to the PBS group. However, this effect was less dramatic in mice treated with antibiotics. While antibiotic treatment did not alter expression of genes associated with apoptosis in 5FU-treated mice, this therapy interfered with upregulation of genes associated with the innate immune response and necroptosis. Our results suggest that oral microbiome depletion decreases the severity of the response to 5FU. Further investigation is needed to dissect the cellular pathways regulated by the microbiome during oral mucositis development.

English

ISBN: 9798384091196Subjects--Topical Terms:

828971
Dentistry.
Subjects--Index Terms:

Cancer chemotherapy

Role of the Oral Microbiome in 5FU-Induced Oral Mucositis /
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520 $a Oral mucositis is a greatly debilitating, yet common complication of cancer chemotherapy. Despite its significance, the pathophysiology of oral mucositis is incompletely understood. Recent clinical studies show that oral microbiome dysbiosis occurs during chemotherapy and is associated with oral mucositis severity. While mucosal damage is a response to chemotherapy toxicity, whether a dysbiotic microbiome influences oral mucosal responses to chemotherapy is unknown. The aim of this study was to evaluate the effects of antibiotic-mediated oral microbiome ablation on oral mucositis utilizing a mouse model. 7-week-old mice received an antibiotic cocktail in drinking water for 7 days followed by 5-fluorouracil (5FU) intraperitoneal injections for 7 days with continued antibiotics. Control groups included mice that did not receive antibiotics prior to 5FU treatment, mice that received the 5FU vehicle (PBS) only and mice that received PBS plus antibiotics. Mice were euthanized on days 4 and 6 after commencing 5FU. Oral bacterial load was evaluated by plating on blood agar. In addition, tongue tissues were stained with toluidine-blue to detect macroscopic lesions. Tongue sections were then subjected to histological examination after hematoxylin and eosin staining and immunohistochemistry for the cell proliferation marker Ki67. Gene expression of selected targets was quantified via RT-qPCR.We observed an increased in oral bacterial load following administration of 5FU, and this change was inhibited by the use of antibiotics. Furthermore, lesions occupied significantly smaller areas of the tongue in mice that received antibiotic treatment. Antibiotics did not prevent the severe atrophy or decreased basal cell layer density of the epithelium caused by 5FU. Mice that received 5FU alone and those that were treated with both 5FU and antibiotics showed decreased Ki67 staining indicative of decreased basal cell proliferation compared to the PBS group. However, this effect was less dramatic in mice treated with antibiotics. While antibiotic treatment did not alter expression of genes associated with apoptosis in 5FU-treated mice, this therapy interfered with upregulation of genes associated with the innate immune response and necroptosis. Our results suggest that oral microbiome depletion decreases the severity of the response to 5FU. Further investigation is needed to dissect the cellular pathways regulated by the microbiome during oral mucositis development.
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