Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy

Zheng, Di‐Wei; Dong, Xue; Pan, Pei; Chen, Ke-Wei; Fan, Jin‐Xuan; Cheng, Si‐Xue; Zhang, Xian‐Zheng

doi:10.1038/s41551-019-0423-2

Cited by 250 publications

(160 citation statements)

References 36 publications

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“…have been consistently associated with this type of cancer, both as a biomarker in the oral cavity (91) and more importantly, in stool and biopsies from tumors samples (21, 84, 87-90, 92, 93), indicating a possible direct effect on the progression of the disease. A more direct indication of the clinical relevance of F. nucleatum in CRC has been presented in a recent paper where the authors show that in mice with colorectal tumors, oral or intravenous administration of dextran nanoparticles covalently linked to azide-modified phages that inhibit the growth of F. nucleatum significantly augments the efficiency of first-line chemotherapy treatments of CRC (102). For all these reasons, most focus has been placed on studying the role of F. nucleatum in CRC.…”

Section: Oral Microorganisms and Cancers Outside The Oral Cavitymentioning

confidence: 99%

The Oral Microbiome and Cancer

2020

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There is mounting evidence that members of the human microbiome are highly associated with a wide variety of cancer types. Among oral cancers, oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied, and it is the most common malignancy of the head and neck worldwide. However, there is a void regarding the role that the oral microbiome may play in OSCC. Previous studies have not consistently found a characteristic oral microbiome composition associated with OSCC. Although a direct causality has not been proven, individual members of the oral microbiome are capable of promoting various tumorigenic functions related to cancer development. Two prominent oral pathogens, Porphyromonas gingivalis, and Fusobacterium nucleatum can promote tumor progression in mice. P. gingivalis infection has been associated with oro-digestive cancer, increased oral cancer invasion, and proliferation of oral cancer stem cells. The microbiome can influence the evolution of the disease by directly interacting with the human body and significantly altering the response and toxicity to various forms of cancer therapy. Recent studies have shown an association of certain phylogenetic groups with the immunotherapy treatment outcomes of certain tumors. On the other side of the coin, recently it has been a resurgence in interest on the potential use of bacteria to cure cancer. These kinds of treatments were used in the late nineteenth and early twentieth centuries as the first line of defense against cancer in some hospitals but later displaced by other types of treatments such as radiotherapy. Currently, organisms such as Salmonella typhimurium and Clostridium spp. have been used for targeted strategies as potential vectors to treat cancer. In this review, we briefly summarize our current knowledge of the role of the oral microbiome, focusing on its bacterial fraction, in cancer in general and in OSCC more precisely, and a brief description of the potential use of bacteria to target tumors.

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Section: Oral Microorganisms and Cancers Outside The Oral Cavitymentioning

confidence: 99%

The Oral Microbiome and Cancer

2020

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“…In view of the potential use of phages for therapeutic purposes and the current understanding of how bacteriophages can impact bacterial communities 21,22 , we evaluated the milk microbial composition at dry-off by means of a culture-independent approach focusing on the relative abundance of the genus Staphylococcus. Moreover, S. aureus UFV2030RH1 was isolated from a dairy cow at drying-off and used to isolate the bacteriophage vB_ SauM-UFV_DC4 existing on the wastewater of a dairy farm.…”

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confidence: 99%

Milk microbial composition of Brazilian dairy cows entering the dry period and genomic comparison between Staphylococcus aureus strains susceptible to the bacteriophage vB_SauM-UFV_DC4

Duarte

Treu

Sartori

et al. 2020

Sci Rep

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Brazil has the second-largest dairy cattle herd in the world, and bovine mastitis still can cause significant losses for dairy farmers. Despite this fact, little information is available about milk microbial composition of Brazilian dairy cows, as well as the potential use of bacteriophages in the control of S. aureus. Here, we investigated milk bacterial composition of 28 Holstein Fresian cows (109 teats), selected in the dry-off period, using 16S rRNA analysis. Furthermore, a representative S. aureus strain (UFV2030RH1) was obtained at drying-off for isolation of a bacteriophage (vB_SauM-UFV_DC4, UFV_DC4) and bacterial genomic comparison purposes. Our outcomes revealed that Staphylococcus was the third most prevalent genus and positively correlated with subclinical mastitis events. As a major finding, genomic analyses showed the presence of adhesive matrix molecules that recognize microbial surface components (MSCRAMM) in UFV2030RH1 and might indicate great biofilm formation capability. A minimum inhibitory concentration (MIC) assay showed that resistance to ampicillin was the highest among the antibiotic tested in S. aureus 3059 and UFV2030RH1, displaying values four and sixteen times greater than MIC resistance breakpoint, respectively. Together, our results suggest that Staphylococcus is highly prevalent in dairy cows at drying-off and the use of the phage UFV_DC4 as a biocontrol agent must be investigated in future studies. In the last few years, dairy activity in Brazil has undergone deep changes, focusing mainly on the improvement of the productive lifetime of dairy cows (i.e. milk production from birth to culling) and the possibility to reduce operation costs. Nowadays, Brazil is the fifth largest global milk producer and it has the second-largest dairy herd in the world, reflecting its relevance to the international dairy market 1. Overall, the cornerstones of a successful dairy farm activity are related to well-established nutritional, genetic and sanitary managements. As regards the latter, bovine mastitis is still the leading cause of economic losses for

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“…We show data proving that controlled local tumor growth and distant metastasis can be achieved within short observation periods when specific cell concentrations and cell lines are applied. Given the tumor growth rates, sizes of tumors, the general good condition of the majority of the animals, and their survival ( Table 1 and Table 2 ), it is very likely that this model can be used to study application of systemic therapies (i.e., chemotherapy) [ 28 , 29 ]. The data collected by this study allow researchers to quickly and easily implement this model for their research and this model can also be adapted to allow tailored experiments depending on their specific research aim (e.g., primary tumor growth, metastasis).…”

Section: Discussionmentioning

confidence: 99%

Establishment of an Endoscopy-Guided Minimally Invasive Orthotopic Mouse Model of Colorectal Cancer

Chen

Neumann

Kühn

et al. 2020

Cancers

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Open orthotopic mouse models of colorectal cancer have disadvantages such as the requirement for advanced surgical skills or the trauma caused by laparotomy. To overcome these drawbacks, this study aimed to evaluate the establishment of a minimally invasive model using murine colonoscopy. CT26 and MC38 CRC cells of different concentrations were injected into BALB/C and C57BL/6J mice, respectively. Follow-up endoscopies were performed to assign an endoscopic score to tumor growth. Gross autopsy, histologic and immuno-histochemical evaluation, and immune scoring were performed. To describe the learning curve of the procedures, a performance score was given. Local tumor growth with colorectal wall infiltration, luminal ulceration, the presence of tumor-infiltrating lymphocytes, lympho-vascular invasion, and early spontaneous lymph node, peritoneal, and hepatic metastases were observed. The tumors showed cytoplasmic immuno-staining for CK20. Compared to the MC38/C57BL/6J model, tumorigenicity and immunogenicity of the CT26/BALB/C model were higher. Tumor volume correlated with the endoscopic score. This endoscopy-guided orthotopic mouse model is easy to learn and quick to establish. It features early metastasis and enables the study of interactions with the immune system. When specific cell concentrations and cell lines are applied, controlled local tumor growth and metastasis can be achieved within short observation periods.

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Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy

Cited by 250 publications

References 36 publications

The Oral Microbiome and Cancer

The Oral Microbiome and Cancer

Milk microbial composition of Brazilian dairy cows entering the dry period and genomic comparison between Staphylococcus aureus strains susceptible to the bacteriophage vB_SauM-UFV_DC4

Establishment of an Endoscopy-Guided Minimally Invasive Orthotopic Mouse Model of Colorectal Cancer

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