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Cancers
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Host-Microbiome Interaction and Cancer
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Host-Microbiome Interaction and Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Infectious Agents and Cancer".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 27568

Special Issue Editors

Dr. Wei Jia

E-Mail Website
Guest Editor
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
Interests: metabolomics; carbon source metabolism and its regulation in cancer cells; gut-microbial-host co-metabolism in gastrointestinal cancers
Special Issues, Collections and Topics in MDPI journals
Dr. Wen Zhou

E-Mail Website
Guest Editor
Cancer Research Institute, Xiangya School of Medicine, Central South University, Hunan 410028, China
Interests: the principle of tumor carcinogenesis and tumor drug resistance; mainly focusing on Multiple Myeloma (MM) as the research object; to explore the molecular mechanism of MM initiation; development and drug resistance; together with the interaction with gut microbiota and host metabolism

Special Issue Information

Dear Colleagues,

Emerging evidence has shown the extensive involvement of host–microbiome interactions in cancer biology. Microbes can promote carcinogenesis directly through their oncogenic proteins and metabolites, and also indirectly through mediating the host’s metabolic, inflammatory and immunological responses. The past decade has witnessed a rapid growth in preclinical and clinical investigations using microbial modulation approaches, ranging from dietary modifications, fecal microbiota transplantation, and pre-/probiotics, to engineered bacteria in cancer therapies. In this Special Issue, we will publish original research articles and reviews that delineate the mechanistic roles of microbiota in cancer development and identify potential diagnostic and modulation strategies involving host-microbiota interactions.

Dr. Wei Jia
Dr. Wen Zhou
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (7 papers)

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Research

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16 pages, 3269 KiB  
Article
Constitutive Expression of a Cytotoxic Anticancer Protein in Tumor-Colonizing Bacteria
by Phuong-Thu Mai, Daejin Lim, EunA So, Ha Young Kim, Taner Duysak, Thanh-Quang Tran, Miryoung Song, Jae-Ho Jeong and Hyon E. Choy
Cancers 2023, 15(5), 1486; https://doi.org/10.3390/cancers15051486 - 27 Feb 2023
Cited by 5 | Viewed by 3198
Abstract
Bacterial cancer therapy is a promising next-generation modality to treat cancer that often uses tumor-colonizing bacteria to deliver cytotoxic anticancer proteins. However, the expression of cytotoxic anticancer proteins in bacteria that accumulate in the nontumoral reticuloendothelial system (RES), mainly the liver and spleen, [...] Read more.
Bacterial cancer therapy is a promising next-generation modality to treat cancer that often uses tumor-colonizing bacteria to deliver cytotoxic anticancer proteins. However, the expression of cytotoxic anticancer proteins in bacteria that accumulate in the nontumoral reticuloendothelial system (RES), mainly the liver and spleen, is considered detrimental. This study examined the fate of the Escherichia coli strain MG1655 and an attenuated strain of Salmonella enterica serovar Gallinarum (S. Gallinarum) with defective ppGpp synthesis after intravenous injection into tumor-bearing mice (~108 colony forming units/animal). Approximately 10% of the injected bacteria were detected initially in the RES, whereas approximately 0.01% were in tumor tissues. The bacteria in the tumor tissue proliferated vigorously to up to 109 colony forming units/g tissue, whereas those in the RES died off. RNA analysis revealed that tumor-associated E. coli activated rrnB operon genes encoding the rRNA building block of ribosome needed most during the exponential stage of growth, whereas those in the RES expressed substantially decreased levels of this gene and were cleared soon presumably by innate immune systems. Based on this finding, we engineered ΔppGpp S. Gallinarum to express constitutively a recombinant immunotoxin comprising TGFα and the Pseudomonas exotoxin A (PE38) using a constitutive exponential phase promoter, the ribosomal RNA promoter rrnB P1. The construct exerted anticancer effects on mice grafted with mouse colon (CT26) or breast (4T1) tumor cells without any notable adverse effects, suggesting that constitutive expression of cytotoxic anticancer protein from rrnB P1 occurred only in tumor tissue. Full article
(This article belongs to the Special Issue Host-Microbiome Interaction and Cancer)
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17 pages, 1436 KiB  
Article
Breast Cancer Survivors and Healthy Women: Could Gut Microbiota Make a Difference?—“BiotaCancerSurvivors”: A Case-Control Study
by Telma Caleça, Pedro Ribeiro, Marina Vitorino, Maria Menezes, Mafalda Sampaio-Alves, Ana Duarte Mendes, Rodrigo Vicente, Ida Negreiros, Ana Faria and Diogo Alpuim Costa
Cancers 2023, 15(3), 594; https://doi.org/10.3390/cancers15030594 - 18 Jan 2023
Cited by 14 | Viewed by 3769
Abstract
In this first analysis, samples from 23 BC survivors (group 1) and 291 healthy female controls (group 2) were characterised through the V3 and V4 regions that encode the “16S rRNA” gene of each bacteria. The samples were sequenced by next-generation sequencing (NGS), [...] Read more.
In this first analysis, samples from 23 BC survivors (group 1) and 291 healthy female controls (group 2) were characterised through the V3 and V4 regions that encode the “16S rRNA” gene of each bacteria. The samples were sequenced by next-generation sequencing (NGS), and the taxonomy was identified by resorting to Kraken2 and improved with Bracken, using a curated database called ‘GutHealth_DB’. The α and β-diversity analyses were used to determine the richness and evenness of the gut microbiota. A non-parametric Mann-Whitney U test was applied to assess differential abundance between both groups. The Firmicutes/Bacteroidetes (F/B) ratio was calculated using a Kruskal-Wallis chi-squared test. The α-diversity was significantly higher in group 1 (p = 0.28 × 10−12 for the Chao index and p = 1.64 × 10−12 for the ACE index). The Shannon index, a marker of richness and evenness, was not statistically different between the two groups (p = 0.72). The microbiota composition was different between the two groups: a null hypothesis was rejected for PERMANOVA (p = 9.99 × 10−5) and Anosim (p = 0.04) and was not rejected for β-dispersion (p = 0.158), using Unifrac weighted distance. The relative abundance of 14 phyla, 29 classes, 25 orders, 64 families, 116 genera, and 74 species differed significantly between both groups. The F/B ratio was significantly lower in group 1 than in group 2, p < 0.001. Our study allowed us to observe significant taxonomic disparities in the two groups by testing the differences between BC survivors and healthy controls. Additional studies are needed to clarify the involved mechanisms and explore the relationship between microbiota and BC survivorship. Full article
(This article belongs to the Special Issue Host-Microbiome Interaction and Cancer)
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17 pages, 4460 KiB  
Article
Intestinal Klebsiella pneumoniae Contributes to Pneumonia by Synthesizing Glutamine in Multiple Myeloma
by Yihui Wang, Qin Yang, Yinghong Zhu, Xingxing Jian, Jiaojiao Guo, Jingyu Zhang, Chunmei Kuang, Xiangling Feng, Gang An, Lugui Qiu, Guancheng Li, Yanjuan He and Wen Zhou
Cancers 2022, 14(17), 4188; https://doi.org/10.3390/cancers14174188 - 29 Aug 2022
Cited by 8 | Viewed by 3451
Abstract
Pneumonia accounts for a significant cause of morbidity and mortality in multiple myeloma (MM) patients. It has been previously shown that intestinal Klebsiella pneumonia (K. pneumonia) enriches in MM and promotes MM progression. However, what role the altered gut microbiota plays [...] Read more.
Pneumonia accounts for a significant cause of morbidity and mortality in multiple myeloma (MM) patients. It has been previously shown that intestinal Klebsiella pneumonia (K. pneumonia) enriches in MM and promotes MM progression. However, what role the altered gut microbiota plays in MM with pneumonia remains unknown. Here, we show that intestinal K. pneumonia is significantly enriched in MM with pneumonia. This enriched intestinal K. pneumonia links to the incidence of pneumonia in MM, and intestinal colonization of K. pneumonia contributes to pneumonia in a 5TGM1 MM mice model. Further targeted metabolomic assays reveal the elevated level of glutamine, which is consistently increased with the enrichment of K. pneumonia in MM mice and patients, is synthesized by K. pneumonia, and leads to the elevated secretion of TNF-α in the lung normal fibroblast cells for the higher incidence of pneumonia. Inhibiting glutamine synthesis by establishing glnA-mutated K. pneumonia alleviates the incidence of pneumonia in the 5TGM1 MM mice model. Overall, our work proposes that intestinal K. pneumonia indirectly contributes to pneumonia in MM by synthesizing glutamine. Altogether, we unveil a gut–lung axis in MM with pneumonia and establish a novel mechanism and a possible intervention strategy for MM with pneumonia. Full article
(This article belongs to the Special Issue Host-Microbiome Interaction and Cancer)
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Review

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18 pages, 1899 KiB  
Review
Intestinal Microbes and Hematological Malignancies
by Yinghong Zhu, Qiaohui Yang, Qin Yang, Yanjuan He and Wen Zhou
Cancers 2023, 15(8), 2284; https://doi.org/10.3390/cancers15082284 - 13 Apr 2023
Cited by 5 | Viewed by 2811
Abstract
Hematological malignancies are diverse, with high malignancy characteristics, poor prognoses, and high mortality rates. The development of hematological malignancies is driven by genetic factors, tumor microenvironment factors, or metabolic factors; however, even when considering all of these factors, one still cannot fully estimate [...] Read more.
Hematological malignancies are diverse, with high malignancy characteristics, poor prognoses, and high mortality rates. The development of hematological malignancies is driven by genetic factors, tumor microenvironment factors, or metabolic factors; however, even when considering all of these factors, one still cannot fully estimate the risk of hematological malignancies. Several recent studies have demonstrated an intimate connection between intestinal microbes and the progression of hematological malignancies, and gut microbes play a primary role in the initiation and progression of hematological tumors through direct and indirect mechanisms. Thus, we summarize the correlation between intestinal microbes and hematological malignancies’ onset, progression, and therapeutic effect in order to better understand how intestinal microbes affect their initiation and progression, especially in leukemia, lymphoma, and multiple myeloma, which may provide potential therapeutic targets for improving the survival of patients with hematological malignancies. Full article
(This article belongs to the Special Issue Host-Microbiome Interaction and Cancer)
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18 pages, 1783 KiB  
Review
The Interaction between Gut Microbiota and Host Amino Acids Metabolism in Multiple Myeloma
by Qin Yang, Yumou Wei, Yinghong Zhu, Jiaojiao Guo, Jingyu Zhang, Yanjuan He, Xin Li, Jing Liu and Wen Zhou
Cancers 2023, 15(7), 1942; https://doi.org/10.3390/cancers15071942 - 23 Mar 2023
Cited by 6 | Viewed by 3200
Abstract
Although novel therapies have dramatically improved outcomes for multiple myeloma (MM) patients, relapse is inevitable and overall outcomes are heterogeneous. The gut microbiota is becoming increasingly recognized for its influence on host metabolism. To date, evidence has suggested that the gut microbiota contributes [...] Read more.
Although novel therapies have dramatically improved outcomes for multiple myeloma (MM) patients, relapse is inevitable and overall outcomes are heterogeneous. The gut microbiota is becoming increasingly recognized for its influence on host metabolism. To date, evidence has suggested that the gut microbiota contributes to MM, not only via the progressive activities of specific bacteria but also through the influence of the microbiota on host metabolism. Importantly, the abnormal amino acid metabolism, as well as the altered microbiome in MM, is becoming increasingly apparent, as is the influence on MM progression and the therapeutic response. Moreover, the gut-microbiota–host-amino-acid metabolism interaction in the progression of MM has been highlighted. Modulation of the gut microbiota (such as fecal microbiota transplantation, FMT) can be modified, representing a new angle in MM treatment that can improve outcomes. In this review, the relationship between gut microbiota, metabolism, and MM, together with strategies to modulate the microbiota, will be discussed, and some unanswered questions for ongoing and future research will be presented. Full article
(This article belongs to the Special Issue Host-Microbiome Interaction and Cancer)
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30 pages, 1099 KiB  
Review
Gut Microbiota and Breast Cancer: The Dual Role of Microbes
by Ana Isabel Álvarez-Mercado, Ana del Valle Cano, Mariana F. Fernández and Luis Fontana
Cancers 2023, 15(2), 443; https://doi.org/10.3390/cancers15020443 - 10 Jan 2023
Cited by 42 | Viewed by 6814
Abstract
Breast cancer is the most frequently diagnosed cancer and also one of the leading causes of mortality among women. The genetic and environmental factors known to date do not fully explain the risk of developing this disease. In recent years, numerous studies have [...] Read more.
Breast cancer is the most frequently diagnosed cancer and also one of the leading causes of mortality among women. The genetic and environmental factors known to date do not fully explain the risk of developing this disease. In recent years, numerous studies have highlighted the dual role of the gut microbiota in the preservation of host health and in the development of different pathologies, cancer among them. Our gut microbiota is capable of producing metabolites that protect host homeostasis but can also produce molecules with deleterious effects, which, in turn, may trigger inflammation and carcinogenesis, and even affect immunotherapy. The purpose of this review is to describe the mechanisms by which the gut microbiota may cause cancer in general, and breast cancer in particular, and to compile clinical trials that address alterations or changes in the microbiota of women with breast cancer. Full article
(This article belongs to the Special Issue Host-Microbiome Interaction and Cancer)
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27 pages, 1565 KiB  
Review
A Review of the Role of Oral Microbiome in the Development, Detection, and Management of Head and Neck Squamous Cell Cancers
by Kimberly M. Burcher, Jack T. Burcher, Logan Inscore, Chance H. Bloomer, Cristina M. Furdui and Mercedes Porosnicu
Cancers 2022, 14(17), 4116; https://doi.org/10.3390/cancers14174116 - 25 Aug 2022
Cited by 18 | Viewed by 3165
Abstract
The role of the microbiome in the development and propagation of head and neck squamous cell cancer (HNSCC) is largely unknown and the surrounding knowledge lags behind what has been discovered related to the microbiome and other malignancies. In this review, the authors [...] Read more.
The role of the microbiome in the development and propagation of head and neck squamous cell cancer (HNSCC) is largely unknown and the surrounding knowledge lags behind what has been discovered related to the microbiome and other malignancies. In this review, the authors performed a structured analysis of the available literature from several databases. The authors discuss the merits and detriments of several studies discussing the microbiome of the structures of the aerodigestive system throughout the development of HNSCC, the role of the microbiome in the development of malignancies (generally and in HNSCC) and clinical applications of the microbiome in HNSCC. Further studies will be needed to adequately describe the relationship between HNSCC and the microbiome, and to push this relationship into a space where it is clinically relevant outside of a research environment. Full article
(This article belongs to the Special Issue Host-Microbiome Interaction and Cancer)
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