The Chicken or the Egg? Changes in Oral Microbiota as Cause or Consequence of Mucositis During Radiation Therapy

Sonis, Stephen T.

doi:10.1016/j.ebiom.2017.03.017

Cited by 25 publications

(21 citation statements)

References 11 publications

(12 reference statements)

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“…It is of note that bacteria can also interfere with biological therapies; nevertheless, no interactions were found with the antibodies used in breast cancer targeted therapy [203]. Finally, the microbiome can modulate the severity of radiation-induced mucositis [244,245] and can protect against radiation-induced toxicity [246].…”

Section: Interference Of the Microbiome And Anticancer Treatmentmentioning

confidence: 99%

Microbiome—Microbial Metabolome—Cancer Cell Interactions in Breast Cancer—Familiar, but Unexplored

Mikó

Kovàcs

Sebő³

et al. 2019

Cells

161

201

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Breast cancer is a leading cause of death among women worldwide. Dysbiosis, an aberrant composition of the microbiome, characterizes breast cancer. In this review we discuss the changes to the metabolism of breast cancer cells, as well as the composition of the breast and gut microbiome in breast cancer. The role of the breast microbiome in breast cancer is unresolved, nevertheless it seems that the gut microbiome does have a role in the pathology of the disease. The gut microbiome secretes bioactive metabolites (reactivated estrogens, short chain fatty acids, amino acid metabolites, or secondary bile acids) that modulate breast cancer. We highlight the bacterial species or taxonomical units that generate these metabolites, we show their mode of action, and discuss how the metabolites affect mitochondrial metabolism and other molecular events in breast cancer. These metabolites resemble human hormones, as they are produced in a “gland” (in this case, the microbiome) and they are subsequently transferred to distant sites of action through the circulation. These metabolites appear to be important constituents of the tumor microenvironment. Finally, we discuss how bacterial dysbiosis interferes with breast cancer treatment through interfering with chemotherapeutic drug metabolism and availability.

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Section: Interference Of the Microbiome And Anticancer Treatmentmentioning

confidence: 99%

Microbiome—Microbial Metabolome—Cancer Cell Interactions in Breast Cancer—Familiar, but Unexplored

Mikó

Kovàcs

Sebő³

et al. 2019

Cells

161

201

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“…However, the specific downstream cellular events mediating oral epithelial damage remain poorly characterized. It has been proposed that oral microbiome communities, which live in constant cross-talk with the adjacent mucosal tissues, could contribute to the development of mucositis [8, 9]. Evidence from animal models of intestinal mucositis suggests it is plausible that epithelial-microbiome cross-talk along the gastrointestinal track modulates susceptibility to mucositis, with resident microbial commensals shown to be necessary for irinotecan-dependent intestinal mucosal injury [10].…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis

et al. 2019

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Background Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. Results Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus , Actinomyces , Gemella , Granulicatella , and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris . Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. Conclusions Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dy...

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“…The overall shift of oral microbiota is another promising diagnostic index for OSCC. Bacteria related to resistance to chemotherapy or radiotherapy are therapeutic targets in the treatment of OSCC (Sonis, 2017). However, studies on the taxonomic characteristic of OSCC tissues and saliva samples are still inadequate.…”

Section: Introductionmentioning

confidence: 99%

Compositional and Functional Analysis of the Microbiome in Tissue and Saliva of Oral Squamous Cell Carcinoma

et al. 2019

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Oral squamous cell carcinoma (OSCC) is affected by the interaction between oral pathogen and holobionts, or the combination of the host and its microbial communities. Studies have indicated the structure and feature of the microbiome in OSCC tissue and saliva, the relationships between microbiota and OSCC sites, stages remain unclear. In the present study, OSCC tissue (T), saliva (S) and mouthwash (W) samples were collected from the same subjects and carried out the microbiome study by 16S sequencing. The results showed the T group was significantly different from the S and W groups with the character of lower richness and diversity. Proteobacteria were most enriched in the T group at the phylum level, while Firmicutes were predominant in groups S and W. At the genus level, the predominant taxa of group T were Acinetobacter and Fusobacterium , and for group S and W, the predominant taxa were Streptococcus and Prevotella . The genera related to late stage tumors were Acinetobacter and Fusobacterium , suggesting microbiota may be implicated in OSCC developing. Both compositional and functional analyses indicated that microbes in tumor tissue were potential indicator for the initiation and development of OSCC.

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The Chicken or the Egg? Changes in Oral Microbiota as Cause or Consequence of Mucositis During Radiation Therapy

Cited by 25 publications

References 11 publications

Microbiome—Microbial Metabolome—Cancer Cell Interactions in Breast Cancer—Familiar, but Unexplored

Microbiome—Microbial Metabolome—Cancer Cell Interactions in Breast Cancer—Familiar, but Unexplored

Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis

Compositional and Functional Analysis of the Microbiome in Tissue and Saliva of Oral Squamous Cell Carcinoma

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