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Ou J, Kang Y, Medlegeh, Fu K, Zhang Y, Yang W. An analysis of the vaginal microbiota and cervicovaginal metabolomics in cervical lesions and cervical carcinoma. Heliyon 2024; 10:e33383. [PMID: 39040371 PMCID: PMC11260971 DOI: 10.1016/j.heliyon.2024.e33383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 05/16/2024] [Accepted: 06/20/2024] [Indexed: 07/24/2024] Open
Abstract
Background To explore the role of vaginal microbiota and metabolomics in the progression of cervical dysplasia. Methods The patient group consists of female patients with low-grade, high-grade cervical dysplasia, and cervical cancer. Normal cervix samples from health volunteers were used as controls. The metabolic fingerprints of cervicovaginal lavage were analyzed using liquid chromatography-mass spectrometry, while the vaginal microbiota was examined through 16S rRNA sequencing. Bioinformatic analysis was adopted to investigate the interplay between hosts and microbes. The vaginal metabolic and microbiota profiles of 90 female patients with cervical dysplasia and 10 controls were analyzed to discover the biological characteristics underlying the progression of cervical cancer. Results We found that Valyl-Glutamate, N, N'-Diacetylbenzidine, and Oxidized glutathione, which were involved in oxidative stress response, were discriminators to distinguish the normal cervix, invasive cervical carcinomas, and CIN3 from others. Cervical carcinoma was characterized by a large variety of vaginal microbes (dominated by non-Lactobacillus communities) compared to the control. These microbes affected amino acid and nucleotide metabolism, producing metabolites with cervical carcinoma and genital inflammation compared to the control group. Conclusions This study revealed that cervicovaginal metabolic profiles were determined by cervical cancer, vaginal microbiota, and their interplays. ROS metabolism can be used to discriminate normal cervix, CIN3, and invasive cervical carcinoma.
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Affiliation(s)
- Jie Ou
- Department of Gyneacology, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
| | - Yanan Kang
- Department of Gyneacology, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
| | - Medlegeh
- Department of Gyneacology, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
| | - Kun Fu
- Department of Gyneacology, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
| | - Yu Zhang
- Department of Gyneacology, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
| | - Wenqing Yang
- Department of Gyneacology, Xiangya Hospital Central South University, Changsha, Hunan, 410008, China
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Fu Y, Li J, Cai W, Huang Y, Liu X, Ma Z, Tang Z, Bian X, Zheng J, Jiang J, Li C. The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions. Acta Pharm Sin B 2024; 14:1560-1591. [PMID: 38572104 PMCID: PMC10985043 DOI: 10.1016/j.apsb.2023.11.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 10/20/2023] [Accepted: 11/03/2023] [Indexed: 04/05/2024] Open
Abstract
Intratumoral microbiota has become research hotspots, and emerges as a non-negligent new component of tumor microenvironments (TME), due to its powerful influence on tumor initiation, metastasis, immunosurveillance and prognosis despite in low-biomass. The accumulations of microbes, and their related components and metabolites within tumor tissues, endow TME with additional pluralistic features which are distinct from the conventional one. Therefore, it's definitely necessary to comprehensively delineate the sophisticated landscapes of tumor microbe microenvironment, as well as their functions and related underlying mechanisms. Herein, in this review, we focused on the fields of tumor microbe microenvironment, including the heterogeneity of intratumor microbiota in different types of tumors, the controversial roles of intratumoral microbiota, the basic features of tumor microbe microenvironment (i.e., pathogen-associated molecular patterns (PAMPs), typical microbial metabolites, autophagy, inflammation, multi-faceted immunomodulation and chemoresistance), as well as the multidisciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes, microbiota metabolites, antibiotics, synthetic biology and rationally designed biomaterials. We hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial, and facilitate the development of microbes-based tumor-specific treatments.
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Affiliation(s)
- Yu Fu
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Jia Li
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Wenyun Cai
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Yulan Huang
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Xinlong Liu
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Zhongyi Ma
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Zhongjie Tang
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Xufei Bian
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
| | - Ji Zheng
- Department of Urology, Urologic Surgery Center, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China
| | - Jiayun Jiang
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Chong Li
- Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China
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Xue C, Gu X, Shi Q, Ma X, Jia J, Su Y, Bao Z, Lu J, Li L. The interaction between intratumoral bacteria and metabolic distortion in hepatocellular carcinoma. J Transl Med 2024; 22:237. [PMID: 38439045 PMCID: PMC10910819 DOI: 10.1186/s12967-024-05036-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 02/24/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND Intratumoral bacteria might play essential roles in tumorigenesis in different cancer types. However, its features and potential roles in hepatocellular carcinoma (HCC) are largely unknown. METHODS In this study, we assessed bacterial RNA by 16S rRNA fluorescence in situ hybridization and detected bacterial lipopolysaccharide (LPS) via immunohistochemistry. Hepa1-6 cells were used to establish orthotopic HCC models in mice. 2bRAD sequencing for microbiome was performed to determine the intratumoral bacterial characteristics, and liquid chromatography-mass spectrometry was conducted to explore the metabolic profile. The potential association between different intratumoral microbiota and metabolites were evaluated. RESULTS We detected bacterial 16S rRNA and LPS in HCC tissues from the patients with HCC. In HCC mouse model, we found that the intratumor bacteria in HCC tissues were significantly different to adjacent nontumor tissues. Furthermore, we observed different metabolites in HCC tissues and adjacent nontumor tissues, such as N-acetyl-D-glucosamine and a-lactose. Our results showed that several bacteria were significantly associated with metabolites, such as Pseudomonas koreensis, which was positively correlated with N-acetyl-D-glucosamine and negatively correlated with citrulline. CONCLUSIONS This study confirmed the close association between different bacteria and metabolites, which might provide novel opportunities for developing new biomarkers and therapeutic targets for HCC.
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Affiliation(s)
- Chen Xue
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xinyu Gu
- Department of Oncology, College of Clinical Medicine, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan, China
| | - Qingmiao Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xiao Ma
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Junjun Jia
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yuanshuai Su
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zhengyi Bao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Juan Lu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
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Abedi A, Tafvizi F, Jafari P, Akbari N. The inhibition effects of Lentilactobacillus buchneri-derived membrane vesicles on AGS and HT-29 cancer cells by inducing cell apoptosis. Sci Rep 2024; 14:3100. [PMID: 38326490 PMCID: PMC10850327 DOI: 10.1038/s41598-024-53773-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 02/05/2024] [Indexed: 02/09/2024] Open
Abstract
In recent years, probiotics and their derivatives have been recognized as important therapeutic agents in the fight against cancer. Therefore, this study aimed to investigate the anticancer effects of membrane vesicles (MVs) from Lentilactobacillus buchneri strain HBUM07105 probiotic isolated from conventional and unprocessed yogurt in Arak province, Iran, against gastric and colon cancer cell lines. The MVs were prepared from the cell-free supernatant (CFS) of L. buchneri and characterized using field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) and SPS-PAGE techniques. The anticancer activity of MVs was evaluated using MTT, flow cytometry, qRT-PCR techniques, and a scratch assay. The study investigated the anti-adenocarcinoma effect of MVs isolated from L. buchneri on a human gastric adenocarcinoma cell line (AGS) and a human colorectal adenocarcinoma cell line (HT-29) at 24, 48, and 72-h time intervals. The results demonstrated that all prepared concentrations (12.5, 25, 50, 100, and 200 µg/mL) of MVs reduced the viability of both types of human adenocarcinoma cells after 24, 48, and 72 h of treatment. The analysis of the apoptosis results revealed that the percentage of AGS and HT-29 cancer cells in the early and late stages of apoptosis was significantly higher after 24, 48, and 72 h of treatment compared to the untreated cancer cells. After treating both AGS and HT-29 cells with the MVs, the cells were arrested in the G0/G1 phase. These microvesicles demonstrate apoptotic activity by increasing the expression of pro-apoptotic genes (BAX, CASP3, and CASP9). According to the scratch test, MVs can significantly decrease the migration of HT-29 and AGS cancer cells after 24, 48, and 72 h of incubation compared to the control groups. The MVs of L. buchneri can also be considered a potential option for inhibiting cancer cell activities.
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Affiliation(s)
- Adel Abedi
- Microbiology Department, Faculty of Science, Arak Branch, Islamic Azad University, Arak, Iran
| | - Farzaneh Tafvizi
- Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran.
| | - Parvaneh Jafari
- Microbiology Department, Faculty of Science, Arak Branch, Islamic Azad University, Arak, Iran.
| | - Neda Akbari
- Microbiology Department, Faculty of Science, Arak Branch, Islamic Azad University, Arak, Iran
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Lyu DW. Immunomodulatory effects of exercise in cancer prevention and adjuvant therapy: a narrative review. Front Physiol 2024; 14:1292580. [PMID: 38239881 PMCID: PMC10794543 DOI: 10.3389/fphys.2023.1292580] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 12/11/2023] [Indexed: 01/22/2024] Open
Abstract
Successful application of cancer immunotherapy has rekindled hope in cancer patients. However, a number of patients are unresponsive to immunotherapy and related treatments. This unresponsiveness in cancer patients toward different treatment regimens can be mainly attributed to severe immune dysfunction in such patients. Several reports indicate that physical exercise can significantly lead to improved cancer patient outcomes. Since exercise gets immense response from the immune system, it can be utilized to improve immune function. Leukocytes with enhanced functions are substantially mobilized into the circulation by a single bout of intense physical exercise. Chronic physical exercise results in greater muscle endurance and strength and improved cardiorespiratory function. This exercise regime is also useful in improving T-cell abundance and reducing dysfunctional T cells. The current available data strongly justify for future clinical trials to investigate physical exercise use as an adjuvant in cancer therapy; however, optimal parameters using exercise for a defined outcome are yet to be established. The components of the immune system associate with almost every tumorigenesis step. The inter-relationship between inflammation, cancer, and innate immunity has recently gained acceptance; however, the underlying cellular and molecular mechanisms behind this relationship are yet to be solved. Several studies suggest physical exercise-mediated induction of immune cells to elicit anti-tumorigenic effects. This indicates the potential of exercising in modulating the behavior of immune cells to inhibit tumor progression. However, further mechanistic details behind physical exercise-driven immunomodulation and anticancer effects have to be determined. This review aims to summarize and discuss the association between physical exercise and immune function modulation and the potential of exercise as an adjuvant therapy in cancer prevention and treatment.
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Affiliation(s)
- Da-wei Lyu
- Physical Education and Health School, East China Jiaotong University, Nanchang, Jiangxi, China
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6
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Medeiros MCD, The S, Bellile E, Russo N, Schmitd L, Danella E, Singh P, Banerjee R, Bassis C, Murphy GR, Sartor MA, Lombaert I, Schmidt TM, Eisbruch A, Murdoch-Kinch CA, Rozek L, Wolf GT, Li G, Chen GY, D'Silva NJ. Salivary microbiome changes distinguish response to chemoradiotherapy in patients with oral cancer. MICROBIOME 2023; 11:268. [PMID: 38037123 PMCID: PMC10687843 DOI: 10.1186/s40168-023-01677-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 09/26/2023] [Indexed: 12/02/2023]
Abstract
BACKGROUND Oral squamous cell carcinoma (SCC) is associated with oral microbial dysbiosis. In this unique study, we compared pre- to post-treatment salivary microbiome in patients with SCC by 16S rRNA gene sequencing and examined how microbiome changes correlated with the expression of an anti-microbial protein. RESULTS Treatment of SCC was associated with a reduction in overall bacterial richness and diversity. There were significant changes in the microbial community structure, including a decrease in the abundance of Porphyromonaceae and Prevotellaceae and an increase in Lactobacillaceae. There were also significant changes in the microbial community structure before and after treatment with chemoradiotherapy, but not with surgery alone. In patients treated with chemoradiotherapy alone, several bacterial populations were differentially abundant between responders and non-responders before and after therapy. Microbiome changes were associated with a change in the expression of DMBT1, an anti-microbial protein in human saliva. Additionally, we found that salivary DMBT1, which increases after treatment, could serve as a post-treatment salivary biomarker that links to microbial changes. Specifically, post-treatment increases in human salivary DMBT1 correlated with increased abundance of Gemella spp., Pasteurellaceae spp., Lactobacillus spp., and Oribacterium spp. This is the first longitudinal study to investigate treatment-associated changes (chemoradiotherapy and surgery) in the oral microbiome in patients with SCC along with changes in expression of an anti-microbial protein in saliva. CONCLUSIONS The composition of the oral microbiota may predict treatment responses; salivary DMBT1 may have a role in modulating the oral microbiome in patients with SCC. After completion of treatment, 6 months after diagnosis, patients had a less diverse and less rich oral microbiome. Leptotrichia was a highly prevalent bacteria genus associated with disease. Expression of DMBT1 was higher after treatment and associated with microbiome changes, the most prominent genus being Gemella Video Abstract.
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Affiliation(s)
- Marcell Costa de Medeiros
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Ave, Room G018, Ann Arbor, MI, 48109-1078, USA
| | - Stephanie The
- Cancer Data Science Shared Resource, University of Michigan Medical School, 1500 E. Medical Center Dr, Ann Arbor, MI, USA
| | - Emily Bellile
- Cancer Data Science Shared Resource, University of Michigan Medical School, 1500 E. Medical Center Dr, Ann Arbor, MI, USA
| | - Nickole Russo
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Ave, Room G018, Ann Arbor, MI, 48109-1078, USA
| | - Ligia Schmitd
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Ave, Room G018, Ann Arbor, MI, 48109-1078, USA
| | - Erika Danella
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Ave, Room G018, Ann Arbor, MI, 48109-1078, USA
| | - Priyanka Singh
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Ave, Room G018, Ann Arbor, MI, 48109-1078, USA
| | - Rajat Banerjee
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Ave, Room G018, Ann Arbor, MI, 48109-1078, USA
| | - Christine Bassis
- Internal Medicine, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI, 331248109, USA
| | - George R Murphy
- Biologic and Materials Sciences and Prosthodontics, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA
- Biointerfaces Institute, Ann Arbor, MI, USA
| | - Maureen A Sartor
- Computational Medicine and Bioinformatics, University of Michigan Medical School, 1500 E. Medical Center Dr, Ann Arbor, MI, USA
| | - Isabelle Lombaert
- Biologic and Materials Sciences and Prosthodontics, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA
- Biointerfaces Institute, Ann Arbor, MI, USA
| | - Thomas M Schmidt
- Microbiology and Immunology, University of Michigan Medical School, 1500 E. Medical Center Dr, Ann Arbor, MI, USA
| | - Avi Eisbruch
- Radiation Oncology, University of Michigan Medical School, 1500 E. Medical Center Dr, Ann Arbor, MI, USA
| | - Carol Anne Murdoch-Kinch
- Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, 1011 North Michigan St, Indianapolis, IN, USA
| | - Laura Rozek
- Environmental Health Sciences, University of Michigan Medical School, 1500 E. Medical Center Dr, Ann Arbor, MI, USA
| | - Gregory T Wolf
- Otolaryngology, University of Michigan Medical School, 1500 E. Medical Center Dr, Ann Arbor, MI, USA
| | - Gen Li
- Biostatistics, University of Michigan School of Public Health, University of Michigan Medical School, 1500 E. Medical Center Dr, Ann Arbor, MI, USA
| | - Grace Y Chen
- Internal Medicine, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI, 331248109, USA.
| | - Nisha J D'Silva
- Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Ave, Room G018, Ann Arbor, MI, 48109-1078, USA.
- Pathology, University of Michigan Medical School, 1500 E. Medical Center Dr, Ann Arbor, MI, USA.
- Rogel Cancer Center, Ann Arbor, MI, USA.
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Naddaf R, Carasso S, Reznick-Levi G, Hasnis E, Qarawani A, Maza I, Gefen T, Half EE, Geva-Zatorsky N. Gut microbial signatures are associated with Lynch syndrome (LS) and cancer history in Druze communities in Israel. Sci Rep 2023; 13:20677. [PMID: 38001152 PMCID: PMC10673896 DOI: 10.1038/s41598-023-47723-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open
Abstract
Lynch syndrome (LS) is a hereditary cancer syndrome caused by autosomal dominant mutations, with high probability of early onset for several cancers, mainly colorectal cancer (CRC). The gut microbiome was shown to be influenced by host genetics and to be altered during cancer development. Therefore, we aimed to determine alterations in gut microbiome compositions of LS patients with and without cancer. We performed fecal microbiome analyses on samples of LS and non-LS members from the Druze ethnoreligious community in Israel, based on both their LS mutation and their cancer history. Our analysis revealed specific bacterial operational taxonomic units (OTUs) overrepresented in LS individuals as well as bacterial OTUs differentiating between the LS individuals with a history of cancer. The identified OTUs align with previous studies either correlating them to pro-inflammatory functions, which can predispose to cancer, or to the cancer itself, and as such, these bacteria can be considered as future therapeutic targets.
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Affiliation(s)
- Rawi Naddaf
- Technion Israel Institute of Technology the Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Technion Integrated Cancer Center, Haifa, Israel
| | - Shaqed Carasso
- Technion Israel Institute of Technology the Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Technion Integrated Cancer Center, Haifa, Israel
| | | | - Erez Hasnis
- Technion Israel Institute of Technology the Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
- Gastroenterology Institute Rambam Health Care Campus, Haifa, Israel
| | - Amalfi Qarawani
- Technion Israel Institute of Technology the Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Technion Integrated Cancer Center, Haifa, Israel
| | - Itay Maza
- Technion Israel Institute of Technology the Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
- Gastroenterology Institute Rambam Health Care Campus, Haifa, Israel
| | - Tal Gefen
- Technion Israel Institute of Technology the Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Technion Integrated Cancer Center, Haifa, Israel
| | - Elizabeth Emily Half
- Technion Israel Institute of Technology the Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel.
- Gastroenterology Institute Rambam Health Care Campus, Haifa, Israel.
| | - Naama Geva-Zatorsky
- Technion Israel Institute of Technology the Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Israel.
- Rappaport Technion Integrated Cancer Center, Haifa, Israel.
- Canadian Institute for Advanced Research, Toronto, ON, Canada.
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Algrafi AS, Jamal AA, Ismaeel DM. Microbiota as a New Target in Cancer Pathogenesis and Treatment. Cureus 2023; 15:e47072. [PMID: 38021696 PMCID: PMC10645418 DOI: 10.7759/cureus.47072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2023] [Indexed: 12/01/2023] Open
Abstract
The microbial ecosystem of humans is an integral part of human health and disease. A significant percentage of tumors worldwide are thought to be microbially induced. The relationship between cancer and microbes is complex. In this article review, we aim to give an overview of human microbiota and its role in carcinogenesis, emphasize the relation between microbiota and cancer immunity, and highlight its role in the future of cancer therapy. The term microbiota refers to the collection of microorganisms that are located in an individual, whereas the total genome of these microorganisms is referred to as the microbiome. The microbiota in humans has many physiological functions. The microbiota within the gut lumen has a profound effect on the local and systemic immune system. The immune system can change the gut microbiota. Microbiota may induce carcinogenesis by several mechanisms. It also affects tumor progression. Thus, microbiota modulation may aid in the prevention and treatment of cancer. Intentionally introducing microorganisms into the oncological patient is assumed to mobilize the immune system to become able to, at least, limit the development of cancer. Microbes are used as vectors which are carriers of particular antineoplastic agents that reduce the side effects of chemotherapy. Inflammation and tumor microenvironment play an essential role in promoting chemo-resistance. There is now considerable evidence, both in humans as well as in laboratory animals, that the commensal microbiota has important effects on carcinogenesis, tumor growth, and therapy response.
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Affiliation(s)
- Abeer S Algrafi
- Internal Medicine, College of Medicine, Taibah University, Madinah, SAU
| | - Aisha A Jamal
- General Practice, College of Medicine, Taibah University, Madinah, SAU
| | - Dana M Ismaeel
- General Practice, College of Medicine, Taibah University, Madinah, SAU
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Elechi JOG, Sirianni R, Conforti FL, Cione E, Pellegrino M. Food System Transformation and Gut Microbiota Transition: Evidence on Advancing Obesity, Cardiovascular Diseases, and Cancers-A Narrative Review. Foods 2023; 12:2286. [PMID: 37372497 PMCID: PMC10297670 DOI: 10.3390/foods12122286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/29/2023] Open
Abstract
Food, a vital component of our daily life, is fundamental to our health and well-being, and the knowledge and practices relating to food have been passed down from countless generations of ancestors. Systems may be used to describe this extremely extensive and varied body of agricultural and gastronomic knowledge that has been gathered via evolutionary processes. The gut microbiota also underwent changes as the food system did, and these alterations had a variety of effects on human health. In recent decades, the gut microbiome has gained attention due to its health benefits as well as its pathological effects on human health. Many studies have shown that a person's gut microbiota partially determines the nutritional value of food and that diet, in turn, shapes both the microbiota and the microbiome. The current narrative review aims to explain how changes in the food system over time affect the makeup and evolution of the gut microbiota, advancing obesity, cardiovascular disease (CVD), and cancer. After a brief discussion of the food system's variety and the gut microbiota's functions, we concentrate on the relationship between the evolution of food system transformation and gut microbiota system transition linked to the increase of non-communicable diseases (NCDs). Finally, we also describe sustainable food system transformation strategies to ensure healthy microbiota composition recovery and maintain the host gut barrier and immune functions to reverse advancing NCDs.
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Affiliation(s)
- Jasper Okoro Godwin Elechi
- Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Italy; (R.S.); (F.L.C.); (E.C.); (M.P.)
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Delaye M, Rousseau A, Mailly-Giacchetti L, Assoun S, Sokol H, Neuzillet C. Obesity, cancer, and response to immune checkpoint inhibitors: Could the gut microbiota be the mechanistic link? Pharmacol Ther 2023:108442. [PMID: 37210004 DOI: 10.1016/j.pharmthera.2023.108442] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 04/27/2023] [Accepted: 05/15/2023] [Indexed: 05/22/2023]
Abstract
Immune checkpoint inhibitors (ICI) have deeply changed the therapeutic management of a broad spectrum of solid tumors. Recent observations showed that obese patients receiving ICIs might have better outcomes than those with normal weight, while obesity was historically associated with a worse prognosis in cancer patients. Of note, obesity is associated with alterations in the gut microbiome profile, which interacts with immune and inflammatory pathways, both at the systemic and intratumoral levels. As the influence of the gut microbiota on the response to ICI has been repeatedly reported, a specific gut microbiome profile in obese cancer patients may be involved in their better response to ICI. This review summarizes recent data on the interactions between obesity, gut microbiota, and ICIs. In addition, we highlight possible pathophysiological mechanisms supporting the hypothesis that gut microbiota could be one of the links between obesity and poor response to ICIs.
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Affiliation(s)
- Matthieu Delaye
- Curie Institute, Department of medical oncology, Versailles Saint-Quentin University, Saint-Cloud, France; GERCOR, 75011 Paris, France
| | - Adrien Rousseau
- Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France
| | - Léah Mailly-Giacchetti
- Department of Medical Oncology, Saint-Louis Hospital, AP-HP.Nord - Université de Paris, Paris, France
| | - Sandra Assoun
- Department of Thoracic Oncology & CIC 1425/CLIP2 Paris-Nord, Bichat-Claude Bernard Hospital, APHP, Paris, France
| | - Harry Sokol
- Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France; Sorbonne Université, INSERM UMRS-938, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Paris, France; INRAE, AgroParisTech, Micalis Institut, 78350, Jouy-en-Josas, France
| | - Cindy Neuzillet
- Curie Institute, Department of medical oncology, Versailles Saint-Quentin University, Saint-Cloud, France; GERCOR, 75011 Paris, France.
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11
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Hassan DS, Hasary HJ, Hassan ZS. Role of Probiotics in the Prevention and Treatment of GIT Cancers: Updated Review. AL-RAFIDAIN JOURNAL OF MEDICAL SCIENCES ( ISSN: 2789-3219 ) 2023; 4:52-59. [DOI: 10.54133/ajms.v4i.103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Cancer, one of the leading causes of death worldwide, has been the subject of extensive study by many researchers. Cancer is affected by both genetic and immune system factors in the human body. The gut microbiota plays an important role in the body's capacity to maintain homeostasis. Because of their beneficial effects on human health and their ability to successfully prevent and treat various chronic diseases, such as cancer, probiotics are becoming increasingly important in medicine. A wealth of research has shown that probiotic consumption can significantly helpful in cancer prevention and treatment. The goal of this review is to provide a thorough overview of the research on the function of probiotic bacteria in the prevention and treatment of gastrointestinal cancers.
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12
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Little A, Tangney M, Tunney MM, Buckley NE. Fusobacterium nucleatum: a novel immune modulator in breast cancer? Expert Rev Mol Med 2023; 25:e15. [PMID: 37009688 PMCID: PMC10407221 DOI: 10.1017/erm.2023.9] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 02/28/2023] [Accepted: 03/06/2023] [Indexed: 04/04/2023]
Abstract
Breast cancer was the most commonly diagnosed cancer worldwide in 2020. Greater understanding of the factors which promote tumour progression, metastatic development and therapeutic resistance is needed. In recent years, a distinct microbiome has been detected in the breast, a site previously thought to be sterile. Here, we review the clinical and molecular relevance of the oral anaerobic bacterium Fusobacterium nucleatum in breast cancer. F. nucleatum is enriched in breast tumour tissue compared with matched healthy tissue and has been shown to promote mammary tumour growth and metastatic progression in mouse models. Current literature suggests that F. nucleatum modulates immune escape and inflammation within the tissue microenvironment, two well-defined hallmarks of cancer. Furthermore, the microbiome, and F. nucleatum specifically, has been shown to affect patient response to therapy including immune checkpoint inhibitors. These findings highlight areas of future research needed to better understand the influence of F. nucleatum in the development and treatment of breast cancer.
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Affiliation(s)
- Alexa Little
- School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Mark Tangney
- Cancer Research, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Michael M. Tunney
- School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Niamh E. Buckley
- School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, UK
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13
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Microbiota-Derived Natural Products Targeting Cancer Stem Cells: Inside the Gut Pharma Factory. Int J Mol Sci 2023; 24:ijms24054997. [PMID: 36902427 PMCID: PMC10003410 DOI: 10.3390/ijms24054997] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/28/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
Cancer stem cells (CSCs) have drawn much attention as important tumour-initiating cells that may also be crucial for recurrence after chemotherapy. Although the activity of CSCs in various forms of cancer is complex and yet to be fully elucidated, opportunities for therapies targeting CSCs exist. CSCs are molecularly distinct from bulk tumour cells, so they can be targeted by exploiting their signature molecular pathways. Inhibiting stemness has the potential to reduce the risk posed by CSCs by limiting or eliminating their capacity for tumorigenesis, proliferation, metastasis, and recurrence. Here, we briefly described the role of CSCs in tumour biology, the mechanisms involved in CSC therapy resistance, and the role of the gut microbiota in cancer development and treatment, to then review and discuss the current advances in the discovery of microbiota-derived natural compounds targeting CSCs. Collectively, our overview suggests that dietary intervention, toward the production of those identified microbial metabolites capable of suppressing CSC properties, is a promising approach to support standard chemotherapy.
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14
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Bae H, Lim SK, Jo HE, Oh Y, Park J, Choi HJ, Yu D. Fecal microbiome in dogs with lymphoid and nonlymphoid tumors. J Vet Intern Med 2023; 37:648-659. [PMID: 36853067 DOI: 10.1111/jvim.16657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 02/03/2023] [Indexed: 03/01/2023] Open
Abstract
BACKGROUND The association of gut microbiota with cancer etiology and prognosis has been demonstrated in humans and rodents but has not been studied in dogs with different types of tumors. HYPOTHESIS/OBJECTIVES To analyze microbiome composition according to tumor progression based on metastasis, recurrence, and therapeutic response in canine tumors. ANIMALS Thirty-two client-owned dogs were divided into 3 groups: healthy (n = 9), with lymphoma (n = 12), with nonlymphoid tumors (n = 11). METHODS Retrospective case series included animals were divided into subgroups according to the nature and severity of their tumors. Feces were screened for the 16S rRNA gene. RESULTS Overall, alpha diversity was significantly reduced in dogs with tumors (n = 23; 12 lymphoid and 11 nonlymphoid) compared to healthy dogs (n = 9). Bacteroides had lower abundance in canine tumors at genus level. Staphylococcus showed significantly reduced abundance in dogs with aggressive tumor progression. Higher white blood cell (WBC) and neutrophil counts and lower hematocrit were significant in dogs with aggressive tumor. Spearman's rank correlation coefficient analysis revealed several measurements that showed moderate to strong correlations, including Coprococcus with total WBC count, neutrophil count, and hematocrit in the aggressive tumor group, and Saccharimonas with serum albumin and sodium concentration in all tumor dogs. CONCLUSION AND CLINICAL IMPORTANCE The diversity of the gut microbiome was significantly reduced in dogs with tumors compared to healthy dogs. Correlations were found between changes in blood measurements and changes in microbiome composition in relation to paraneoplastic syndrome.
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Affiliation(s)
- Hyeona Bae
- College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea
| | - Seul Ki Lim
- Technology Innovation Research Division, World Institute of Kimchi, Gwangju, South Korea
| | - Hee Eun Jo
- Technology Innovation Research Division, World Institute of Kimchi, Gwangju, South Korea.,Department of Biomedical Sciences Graduate School, Chonnam National University, Gwangju, South Korea
| | - Yeonsu Oh
- College of Veterinary Medicine, Kangwon National University, Chuncheon, South Korea
| | - Jinho Park
- College of Veterinary Medicine, Chonbuk National University, Iksan, South Korea
| | - Hak-Jong Choi
- Technology Innovation Research Division, World Institute of Kimchi, Gwangju, South Korea
| | - DoHyeon Yu
- College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea
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15
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Deepening Our Understanding of the Factors Affecting Landscape of Myeloproliferative Neoplasms: What Do We Know about Them? Cancers (Basel) 2023; 15:cancers15041348. [PMID: 36831689 PMCID: PMC9954305 DOI: 10.3390/cancers15041348] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 02/15/2023] [Accepted: 02/17/2023] [Indexed: 02/25/2023] Open
Abstract
Myeloproliferative neoplasms (MPNs) arise from the uncontrolled proliferation of hematopoietic stem and progenitor cells in bone marrow. As with all tumors, the development of MPNs is a consequence of alterations in malignant cells and their interaction with other extrinsic factors that support and promote tumor progression. Since the discovery of driver mutations, much work has focused on studying and reviewing the genomic features of the disease but has neglected to delve into the important role that many other mechanisms may play. This review discusses the genetic component of MPNs but focuses mainly on some of the most relevant work investigating other non-genetic factors that may be crucial for the disease. The studies summarized here address MPN cell-intrinsic or -extrinsic factors and the interaction between them through transcriptomic, proteomic and microbiota studies, among others.
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16
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Colon Cancer Microbiome Landscaping: Differences in Right- and Left-Sided Colon Cancer and a Tumor Microbiome-Ileal Microbiome Association. Int J Mol Sci 2023; 24:ijms24043265. [PMID: 36834671 PMCID: PMC9963782 DOI: 10.3390/ijms24043265] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 02/01/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023] Open
Abstract
In the current era of precision oncology, it is widely acknowledged that CRC is a heterogeneous disease entity. Tumor location (right- or left-sided colon cancer or rectal cancer) is a crucial factor in determining disease progression as well as prognosis and influences disease management. In the last decade, numerous works have reported that the microbiome is an important element of CRC carcinogenesis, progression and therapy response. Owing to the heterogeneous nature of microbiomes, the findings of these studies were inconsistent. The majority of the studies combined colon cancer (CC) and rectal cancer (RC) samples as CRC for analysis. Furthermore, the small intestine, as the major site for immune surveillance in the gut, is understudied compared to the colon. Thus, the CRC heterogeneity puzzle is far from being solved, and more research is necessary for prospective trials that separately investigate CC and RC. Our prospective study aimed to map the colon cancer landscape using 16S rRNA amplicon sequencing in biopsy samples from the terminal ileum, healthy colon tissue, healthy rectal tissue and tumor tissue as well as in preoperative and postoperative stool samples of 41 patients. While fecal samples provide a good approximation of the average gut microbiome composition, mucosal biopsies allow for detecting subtle variations in local microbial communities. In particular, the small bowel microbiome has remained poorly characterized, mainly because of sampling difficulties. Our analysis revealed the following: (i) right- and left-sided colon cancers harbor distinct and diverse microbiomes, (ii) the tumor microbiome leads to a more consistent cancer-defined microbiome between locations and reveals a tumor microbiome-ileal microbiome association, (iii) the stool only partly reflects the microbiome landscape in patients with CC, and (iv) mechanical bowel preparation and perioperative antibiotics together with surgery result in major changes in the stool microbiome, characterized by a significant increase in the abundance of potentially pathogenic bacteria, such as Enterococcus. Collectively, our results provide new and valuable insights into the complex microbiome landscape in patients with colon cancer.
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17
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Sayin S, Rosener B, Li CG, Ho B, Ponomarova O, Ward DV, Walhout AJM, Mitchell A. Evolved bacterial resistance to the chemotherapy gemcitabine modulates its efficacy in co-cultured cancer cells. eLife 2023; 12:83140. [PMID: 36734518 PMCID: PMC9931390 DOI: 10.7554/elife.83140] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 01/22/2023] [Indexed: 02/04/2023] Open
Abstract
Drug metabolism by the microbiome can influence anticancer treatment success. We previously suggested that chemotherapies with antimicrobial activity can select for adaptations in bacterial drug metabolism that can inadvertently influence the host's chemoresistance. We demonstrated that evolved resistance against fluoropyrimidine chemotherapy lowered its efficacy in worms feeding on drug-evolved bacteria (Rosener et al., 2020). Here, we examine a model system that captures local interactions that can occur in the tumor microenvironment. Gammaproteobacteria-colonizing pancreatic tumors can degrade the nucleoside-analog chemotherapy gemcitabine and, in doing so, can increase the tumor's chemoresistance. Using a genetic screen in Escherichia coli, we mapped all loss-of-function mutations conferring gemcitabine resistance. Surprisingly, we infer that one third of top resistance mutations increase or decrease bacterial drug breakdown and therefore can either lower or raise the gemcitabine load in the local environment. Experiments in three E. coli strains revealed that evolved adaptation converged to inactivation of the nucleoside permease NupC, an adaptation that increased the drug burden on co-cultured cancer cells. The two studies provide complementary insights on the potential impact of microbiome adaptation to chemotherapy by showing that bacteria-drug interactions can have local and systemic influence on drug activity.
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Affiliation(s)
- Serkan Sayin
- Department of Systems Biology, University of Massachusetts Chan Medical SchoolWorcesterUnited States
| | - Brittany Rosener
- Department of Systems Biology, University of Massachusetts Chan Medical SchoolWorcesterUnited States
| | - Carmen G Li
- Department of Systems Biology, University of Massachusetts Chan Medical SchoolWorcesterUnited States
| | - Bao Ho
- Department of Systems Biology, University of Massachusetts Chan Medical SchoolWorcesterUnited States
| | - Olga Ponomarova
- Department of Systems Biology, University of Massachusetts Chan Medical SchoolWorcesterUnited States
| | - Doyle V Ward
- Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical SchoolWorcesterUnited States
- Program in Microbiome Dynamics, University of Massachusetts Chan Medical SchoolWorcesterUnited States
| | - Albertha JM Walhout
- Department of Systems Biology, University of Massachusetts Chan Medical SchoolWorcesterUnited States
- Program in Molecular Medicine, University of Massachusetts Chan Medical SchoolWorcesterUnited States
| | - Amir Mitchell
- Department of Systems Biology, University of Massachusetts Chan Medical SchoolWorcesterUnited States
- Program in Microbiome Dynamics, University of Massachusetts Chan Medical SchoolWorcesterUnited States
- Program in Molecular Medicine, University of Massachusetts Chan Medical SchoolWorcesterUnited States
- Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical SchoolWorcesterUnited States
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18
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Zhu Z, Cai J, Hou W, Xu K, Wu X, Song Y, Bai C, Mo YY, Zhang Z. Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice. Gut Microbes 2023; 15:2166700. [PMID: 36740846 PMCID: PMC9904296 DOI: 10.1080/19490976.2023.2166700] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Although gut microbiota has been linked to cancer, little is known about the crosstalk between gut- and intratumoral-microbiomes. The goal of this study was to determine whether gut Akkermansia muciniphila (Akk) is involved in the regulation of intratumoral microbiome and metabolic contexture, leading to an anticancer effect on lung cancer. We evaluated the effects of gut endogenous or gavaged exogenous Akk on the tumorigenesis using the Lewis lung cancer mouse model. Feces, blood, and tumor tissue samples were collected for 16S rDNA sequencing. We then conducted spatially resolved metabolomics profiling to discover cancer metabolites in situ directly and to characterize the overall Akk-regulated metabolic features, followed by the correlation analysis of intratumoral bacteria with metabolic network. Our results showed that both endogenous and exogenous gavaged Akk significantly inhibited tumorigenesis. Moreover, we detected increased Akk abundance in blood circulation or tumor tissue by 16S rDNA sequencing in the Akk gavaged mice, compared with the control mice. Of great interest, gavaged Akk may migrate into tumor tissue and influence the composition of intratumoral microbiome. Spatially resolved metabolomics analysis revealed that the gut-derived Akk was able to regulate tumor metabolic pathways, from metabolites to enzymes. Finally, our study identified a significant correlation between the gut Akk-regulated intratumoral bacteria and metabolic network. Together, gut-derived Akk may migrate into blood circulation, and subsequently colonize into lung cancer tissue, which contributes to the suppression of tumorigenesis by influencing tumoral symbiotic microbiome and reprogramming tumoral metabolism, although more studies are needed.
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Affiliation(s)
- Zhuxian Zhu
- Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China,CONTACT Yin-Yuan MoInstitute of Clinical Medicine, Zhejiang Provincial People’s Hospital of Hangzhou Medical College, Hangzhou, China
| | - Jixu Cai
- Department of Emergency Medicine, Tongji University School of Medicine, Shanghai, China
| | - Weiwei Hou
- Department of Clinical Laboratory, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ke Xu
- Department of General Medicine, Tongji University School of Medicine, Shanghai, China
| | - Xuxiao Wu
- Department of Emergency Medicine, Tongji University School of Medicine, Shanghai, China
| | - Yuanlin Song
- Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chunxue Bai
- Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yin-Yuan Mo
- Institute of Clinical Medicine, Zhejiang Provincial People’s Hospital of Hangzhou Medical College, Hangzhou, China
| | - Ziqiang Zhang
- Department of Infectious Disease, Tongji Hospital, Tongji University School of Medicine, Shanghai, China,Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China,Ziqiang Zhang Department of Infectious Disease, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
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19
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Ricci F, Leggat W, Page CE, Ainsworth TD. Coral growth anomalies, neoplasms, and tumors in the Anthropocene. Trends Microbiol 2022; 30:1160-1173. [PMID: 35718641 DOI: 10.1016/j.tim.2022.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 05/19/2022] [Accepted: 05/23/2022] [Indexed: 01/13/2023]
Abstract
One of the most widespread coral diseases linked to anthropogenic activities and recorded on reefs worldwide is characterized by anomalous growth formations in stony corals, referred to as coral growth anomalies (GAs). The biological functions of GA tissue include limited reproduction, reduced access to resources, and weakened ability to defend against predators. Transcriptomic analyses have revealed that, in some cases, disease progression can involve host genes related to oncogenesis, suggesting that the GA tissues may be malignant neoplasms such as those developed by vertebrates. The number of studies reporting the presence of GAs in common reef-forming species highlights the urgency of a thorough understanding of the pathology and causative factors of this disease and its parallels to higher organism malignant tissue growth. Here, we review the current state of knowledge on the etiology and holobiont features of GAs in reef-building corals.
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Affiliation(s)
- Francesco Ricci
- University of New South Wales, School of Biological, Earth and Environmental Sciences, Kensington 2033, NSW, Australia.
| | - William Leggat
- University of Newcastle, School of Environmental and Life Sciences, Callaghan 2309, NSW, Australia
| | - Charlotte E Page
- University of New South Wales, School of Biological, Earth and Environmental Sciences, Kensington 2033, NSW, Australia
| | - Tracy D Ainsworth
- University of New South Wales, School of Biological, Earth and Environmental Sciences, Kensington 2033, NSW, Australia
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20
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Boytar AN, Nitert MD, Morrision M, Skinner TL, Jenkins DG. Exercise-induced changes to the human gut microbiota and implications for colorectal cancer: a narrative review. J Physiol 2022; 600:5189-5201. [PMID: 36369926 PMCID: PMC10099575 DOI: 10.1113/jp283702] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 10/18/2022] [Indexed: 11/15/2022] Open
Abstract
Physical activity is associated with reduced risks of colorectal cancer (CRC) incidence, recurrence and mortality. While these findings are consistent, the mechanism/s underlying this association remain unclear. Growing evidence supports the many ways in which differing characteristics of the gut microbiota can be tumourigenic or protective against CRC. CRC is characterised by significant dysbiosis including reduced short chain fatty acid-producing bacteria. Recent findings suggest that exercise can modify the gut microbiota, and these changes are inverse to the changes seen with CRC; however, this exercise-microbiota interaction is currently understudied in CRC. This review summarises parallel areas of research that are rapidly developing: The exercise-gut microbiota research and cancer-gut microbiota research and highlights the salient similarities. Preliminary evidence suggests that these areas are linked, with exercise mediating changes that promote the antitumorigenic characteristics of the gut microbiota. Future mechanistic and population-specific studies are warranted to confirm the physiological mechanism/s by which exercise changes the gut microbiota, and the influence of the exercise-gut interaction on cancer specific outcomes in CRC.
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Affiliation(s)
- Alexander N Boytar
- School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, Australia
| | - Marloes Dekker Nitert
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia
| | - Mark Morrision
- The University of Queensland Diamantina Institute, Faculty of Medicine, Translational Research Institute, The University of Queensland, Brisbane, Australia
| | - Tina L Skinner
- School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, Australia
| | - David G Jenkins
- School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, Australia.,University of the Sunshine Coast, Maroochydore, Australia.,Applied Sports Science Technology and Medicine Research Centre, Swansea University, Wales, UK
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21
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Moreira FC, Sarquis DP, de Souza JES, Avelar DDS, Araújo TMT, Khayat AS, dos Santos SEB, de Assumpção PP. Treasures from trash in cancer research. Oncotarget 2022; 13:1246-1257. [PMID: 36395362 PMCID: PMC9671455 DOI: 10.18632/oncotarget.28308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 10/26/2022] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Cancer research has significantly improved in recent years, primarily due to next-generation sequencing (NGS) technology. Consequently, an enormous amount of genomic and transcriptomic data has been generated. In most cases, the data needed for research goals are used, and unwanted reads are discarded. However, these eliminated data contain relevant information. Aiming to test this hypothesis, genomic and transcriptomic data were acquired from public datasets. MATERIALS AND METHODS Metagenomic tools were used to explore genomic cancer data; additional annotations were used to explore differentially expressed ncRNAs from miRNA experiments, and variants in adjacent to tumor samples from RNA-seq experiments were also investigated. RESULTS In all analyses, new data were obtained: from DNA-seq data, microbiome taxonomies were characterized with a similar performance of dedicated metagenomic research; from miRNA-seq data, additional differentially expressed sncRNAs were found; and in tumor and adjacent to tumor tissue data, somatic variants were found. CONCLUSIONS These findings indicate that unexplored data from NGS experiments could help elucidate carcinogenesis and discover putative biomarkers with clinical applications. Further investigations should be considered for experimental design, providing opportunities to optimize data, saving time and resources while granting access to multiple genomic perspectives from the same sample and experimental run.
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Affiliation(s)
- Fabiano Cordeiro Moreira
- Núcleo de Pesquisas em Oncologia/Universidade Federal do Pará, Belém, Pará, Brazil
- Co-first authors
| | - Dionison Pereira Sarquis
- Núcleo de Pesquisas em Oncologia/Universidade Federal do Pará, Belém, Pará, Brazil
- Co-first authors
| | | | | | | | - André Salim Khayat
- Núcleo de Pesquisas em Oncologia/Universidade Federal do Pará, Belém, Pará, Brazil
| | - Sidney Emanuel Batista dos Santos
- Núcleo de Pesquisas em Oncologia/Universidade Federal do Pará, Belém, Pará, Brazil
- Instituto de Ciências Biológicas/Universidade Federal do Pará, Belém, Pará, Brazil
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22
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Steiner HE, Patterson HK, Giles JB, Karnes JH. Bringing pharmacomicrobiomics to the clinic through well-designed studies. Clin Transl Sci 2022; 15:2303-2315. [PMID: 35899413 PMCID: PMC9579385 DOI: 10.1111/cts.13381] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 07/05/2022] [Accepted: 07/15/2022] [Indexed: 01/25/2023] Open
Abstract
Pharmacomicrobiomic studies investigate drug-microbiome interactions, such as the effect of microbial variation on drug response and disposition. Studying and understanding the interactions between the gut microbiome and drugs is becoming increasingly relevant to clinical practice due to its potential for avoiding adverse drug reactions or predicting variability in drug response. The highly variable nature of the human microbiome presents significant challenges to assessing microbes' influence. Studies aiming to explore drug-microbiome interactions should be well-designed to account for variation in the microbiome over time and collect data on confounders such as diet, disease, concomitant drugs, and other environmental factors. Here, we assemble a set of important considerations and recommendations for the methodological features required for performing a pharmacomicrobiomic study in humans with a focus on the gut microbiome. Consideration of these factors enable discovery, reproducibility, and more accurate characterization of the relationships between a given drug and the microbiome. Furthermore, appropriate interpretation and dissemination of results from well-designed studies will push the field closer to clinical relevance and implementation.
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Affiliation(s)
- Heidi E. Steiner
- Department of Pharmacy Practice and ScienceUniversity of Arizona R. Ken Coit College of PharmacyTucsonArizonaUSA
| | - Hayley K. Patterson
- Department of Pharmacy Practice and ScienceUniversity of Arizona R. Ken Coit College of PharmacyTucsonArizonaUSA
| | - Jason B. Giles
- Department of Pharmacy Practice and ScienceUniversity of Arizona R. Ken Coit College of PharmacyTucsonArizonaUSA
| | - Jason H. Karnes
- Department of Pharmacy Practice and ScienceUniversity of Arizona R. Ken Coit College of PharmacyTucsonArizonaUSA,Department of Biomedical InformaticsVanderbilt University Medical CenterNashvilleTennesseeUSA
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23
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Quazi S. Anti-cancer activity of human gastrointestinal bacteria. Med Oncol 2022; 39:220. [PMID: 36175586 DOI: 10.1007/s12032-022-01771-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 06/14/2022] [Indexed: 06/16/2023]
Abstract
Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human's gastrointestinal tract can create immune response against inflammation and also can develop diseases, including cancer. The bacteria of the gastrointestinal tract of human can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.
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Affiliation(s)
- Sameer Quazi
- GenLab Biosolutions Private Limited, Bangalore, 560043, Karnataka, India.
- Department of Biomedical Sciences, School of Life Sciences, Anglia Ruskin University, Cambridge, UK.
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24
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Kapsetaki SE, Marquez Alcaraz G, Maley CC, Whisner CM, Aktipis A. Diet, Microbes, and Cancer Across the Tree of Life: a Systematic Review. Curr Nutr Rep 2022; 11:508-525. [PMID: 35704266 PMCID: PMC9197725 DOI: 10.1007/s13668-022-00420-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2022] [Indexed: 11/09/2022]
Abstract
PURPOSE OF REVIEW Cancers are a leading cause of death in humans and for many other species. Diet has often been associated with cancers, and the microbiome is an essential mediator between diet and cancers. Here, we review the work on cancer and the microbiome across species to search for broad patterns of susceptibility associated with different microbial species. RECENT FINDINGS Some microbes, such as Helicobacter bacteria, papillomaviruses, and the carnivore-associated Fusobacteria, consistently induce tumorigenesis in humans and other species. Other microbes, such as the milk-associated Lactobacillus, consistently inhibit tumorigenesis in humans and other species. We systematically reviewed over a thousand published articles and identified links between diet, microbes, and cancers in several species of mammals, birds, and flies. Future work should examine a larger variety of host species to discover new model organisms for human preclinical trials, to better understand the observed variance in cancer prevalence across species, and to discover which microbes and diets are associated with cancers across species. Ultimately, this could help identify microbial and dietary interventions to diagnose, prevent, and treat cancers in humans as well as other animals.
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Affiliation(s)
- Stefania E Kapsetaki
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA.
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA.
| | - Gissel Marquez Alcaraz
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA
| | - Carlo C Maley
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA
| | - Corrie M Whisner
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
| | - Athena Aktipis
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Department of Psychology, Arizona State University, Tempe, AZ, USA
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25
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Hooper MJ, LeWitt TM, Veon FL, Pang Y, Chlipala GE, Feferman L, Green SJ, Sweeney D, Bagnowski KT, Burns MB, Seed PC, Guitart J, Zhou XA. Nasal Dysbiosis in Cutaneous T-Cell Lymphoma Is Characterized by Shifts in Relative Abundances of Non- Staphylococcus Bacteria. JID INNOVATIONS 2022; 2:100132. [PMID: 36161104 PMCID: PMC9500465 DOI: 10.1016/j.xjidi.2022.100132] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 04/06/2022] [Accepted: 04/08/2022] [Indexed: 12/26/2022] Open
Abstract
The nasal microbiome of patients with cutaneous T-cell lymphoma (CTCL) remains unexplored despite growing evidence connecting nasal bacteria to skin health and disease. Nasal swabs from 45 patients with CTCL (40 with mycosis fungoides, 5 with Sézary syndrome) and 20 healthy controls from the same geographical region (Chicago Metropolitan Area, Chicago, IL) were analyzed using sequencing of 16S ribosomal RNA and tuf2 gene amplicons. Nasal α-diversity did not differ between mycosis fungoides/Sézary syndrome and healthy controls (Shannon index, genus level, P = 0.201), but distinct microbial communities were identified at the class (R2 = 0.104, P = 0.023) and order (R2 = 0.0904, P = 0.038) levels. Increased relative abundance of the genera Catenococcus, Vibrio, Roseomonas, Acinetobacter, and unclassified Clostridiales was associated with increased skin disease burden (P < 0.005, q < 0.05). Performed to accurately resolve nasal Staphylococcus at the species level, tuf2 gene amplicon sequencing revealed no significant differences between mycosis fungoides/Sézary syndrome and healthy controls. Although S. aureus has been shown to worsen CTCL through its toxins, no increase in the relative abundance of this taxon was observed in nasal samples. Despite the lack of differences in Staphylococcus, the CTCL nasal microbiome was characterized by shifts in numerous other bacterial taxa. These data add to our understanding of the greater CTCL microbiome and provide context for comprehending nasal-skin and host‒tumor‒microbial relationships.
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Affiliation(s)
- Madeline J. Hooper
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Tessa M. LeWitt
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Francesca L. Veon
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Yanzhen Pang
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - George E. Chlipala
- Research Informatics Core, Research Resources Center, University of Illinois Chicago, Chicago, Illinois, USA
| | - Leo Feferman
- Research Informatics Core, Research Resources Center, University of Illinois Chicago, Chicago, Illinois, USA
| | - Stefan J. Green
- Rush Genomics and Microbiome Core Facility, Rush University Medical Center, Chicago, Illinois, USA
| | - Dagmar Sweeney
- Genome Research Core, Genome Research Division, Research Resources Center, University of Illinois Chicago, Chicago, Illinois, USA
| | - Katherine T. Bagnowski
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Michael B. Burns
- Department of Biology, Loyola University Chicago, Chicago, Illinois, USA
| | - Patrick C. Seed
- Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
| | - Joan Guitart
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Xiaolong A. Zhou
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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Polyphenols–Gut–Heart: An Impactful Relationship to Improve Cardiovascular Diseases. Antioxidants (Basel) 2022; 11:antiox11091700. [PMID: 36139775 PMCID: PMC9495581 DOI: 10.3390/antiox11091700] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/25/2022] [Accepted: 08/26/2022] [Indexed: 11/30/2022] Open
Abstract
A healthy gut provides the perfect habitat for trillions of bacteria, called the intestinal microbiota, which is greatly responsive to the long-term diet; it exists in a symbiotic relationship with the host and provides circulating metabolites, hormones, and cytokines necessary for human metabolism. The gut–heart axis is a novel emerging concept based on the accumulating evidence that a perturbed gut microbiota, called dysbiosis, plays a role as a risk factor in the pathogenesis of cardiovascular disease. Consequently, recovery of the gut microbiota composition and function could represent a potential new avenue for improving patient outcomes. Despite their low absorption, preclinical evidence indicates that polyphenols and their metabolites are transformed by intestinal bacteria and halt detrimental microbes’ colonization in the host. Moreover, their metabolites are potentially effective in human health due to antioxidant, anti-inflammatory, and anti-cancer effects. The aim of this review is to provide an overview of the causal role of gut dysbiosis in the pathogenesis of atherosclerosis, hypertension, and heart failure; to discuss the beneficial effects of polyphenols on the intestinal microbiota, and to hypothesize polyphenols or their derivatives as an opportunity to prevent and treat cardiovascular diseases by shaping gut eubiosis.
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27
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Yuan L, Yang P, Wei G, Hu X, Chen S, Lu J, Yang L, He X, Bao G. Tumor microbiome diversity influences papillary thyroid cancer invasion. Commun Biol 2022; 5:864. [PMID: 36002642 PMCID: PMC9402670 DOI: 10.1038/s42003-022-03814-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 08/08/2022] [Indexed: 11/09/2022] Open
Abstract
Papillary thyroid carcinoma (PTC) has a high incidence, and its proper treatment remains challenging. Therefore, identifying PTC progression markers is essential. Here, using 16S RNA sequences, we analyzed the PTC intratumor microbiome and its role in tumor progression. Substantial microbial abundance was detected in PTC from all patients. The tumor bacterial diversity in patients with advanced lesions (T3/T4) was significantly higher than that in patients with relatively mild lesions (T1/T2). Importantly, we identified signatures of eight tumor bacterial taxa highly predictive of PTC invasion status. Hence, microbial host factors-independent of the genomic composition of the tumor-may determine tumor behaviors and patient outcomes. Furthermore, the correlation between specific bacterial genus and thyroid hormones or autoimmune thyroid disease-related antibodies may indicate the potential contribution of the microbiome in the relationship between autoimmune thyroid disease or irregular thyroid function and PTC progression, intervention of which might therefore be worth exploring for advancing oncology care.
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Affiliation(s)
- Lijuan Yuan
- Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China
| | - Ping Yang
- Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China
| | - Gang Wei
- Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China
| | - Xi'e Hu
- Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China
| | - Songhao Chen
- Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China
| | - Jianguo Lu
- Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China
| | - Lin Yang
- Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China
| | - Xianli He
- Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China.
| | - Guoqiang Bao
- Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, China.
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Zhu W, Wang JZ, Liu Z, Wei JF. The bacteria inside human cancer cells: Mainly as cancer promoters. Front Oncol 2022; 12:897330. [PMID: 36033476 PMCID: PMC9411745 DOI: 10.3389/fonc.2022.897330] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 07/14/2022] [Indexed: 11/24/2022] Open
Abstract
The roles of the microbiome in human beings have become clearer with the development of next-generation sequencing techniques. Several pieces of evidence showed strong correlations between the microbiome and human health and disease, such as metabolic disorders, infectious diseases, digestive system diseases, and cancers. Among these diverse microbiomes, the role of bacteria in human cancers, especially in cancer cells, has received extensive attention. Latest studies found that bacteria widely existed in cancers, mainly in cancer cells and immune cells. In this review, we summarize the latest advances in understanding the role of bacteria in human cancer cells. We also discuss how bacteria are transported into cancer cells and their physiological significance in cancer progression. Finally, we present the prospect of bacterial therapy in cancer treatment.
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Affiliation(s)
- Wei Zhu
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
- Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jing-Zi Wang
- Department of Urology, Children’s Hospital of Nanjing Medical University, Nanjing, China
| | - Zhixian Liu
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Ji-Fu Wei
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
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29
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Smythe P, Efthimiou G. In Silico Genomic and Metabolic Atlas of Limosilactobacillus reuteri DSM 20016: An Insight into Human Health. Microorganisms 2022; 10:microorganisms10071341. [PMID: 35889060 PMCID: PMC9320016 DOI: 10.3390/microorganisms10071341] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/29/2022] [Accepted: 06/30/2022] [Indexed: 11/23/2022] Open
Abstract
Probiotics are bacterial strains that are known to provide host health benefits. Limosilactobacillus reuteri is a well-documented lactic acid bacterium that has been cultured from numerous human sites. The strain investigated was L. reuteri DSM 20016, which has been found to produce useful metabolites. The strain was explored using genomic and proteomic tools, manual searches, and databases, including KEGG, STRING, BLAST Sequence Similarity Search, and UniProt. This study located over 200 key genes that were involved in human health benefit pathways. L. reuteri DSM 20016 has metabolic pathways to produce acetate, propionate, and lactate, and there is evidence of a pathway for butanoate production through a FASII mechanism. The bacterium produces histamine through the hdc operon, which may be able to suppress proinflammatory TNF, and the bacterium also has the ability to synthesize folate and riboflavin, although whether they are secreted is yet to be explored. The strain can bind to human Caco2 cells through srtA, mapA/cnb, msrB, and fbpA and can compete against enteric bacteria using reuterin, which is an antimicrobial that induces oxidative stress. The atlas could be used for designing metabolic engineering approaches to improve beneficial metabolite biosynthesis and better probiotic-based cures.
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Affiliation(s)
- Paisleigh Smythe
- Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, Castle Hill Hospital, Daisy Building, Hull HU16 5JQ, UK;
| | - Georgios Efthimiou
- Department of Biomedical and Forensic Sciences, University of Hull, Cottingham Road, Hardy Building, Hull HU6 7RX, UK
- Correspondence: ; Tel.: +44-(0)1482-465970
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30
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Dawood A, Algharib SA, Zhao G, Zhu T, Qi M, Delai K, Hao Z, Marawan MA, Shirani I, Guo A. Mycoplasmas as Host Pantropic and Specific Pathogens: Clinical Implications, Gene Transfer, Virulence Factors, and Future Perspectives. Front Cell Infect Microbiol 2022; 12:855731. [PMID: 35646746 PMCID: PMC9137434 DOI: 10.3389/fcimb.2022.855731] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 04/04/2022] [Indexed: 12/28/2022] Open
Abstract
Mycoplasmas as economically important and pantropic pathogens can cause similar clinical diseases in different hosts by eluding host defense and establishing their niches despite their limited metabolic capacities. Besides, enormous undiscovered virulence has a fundamental role in the pathogenesis of pathogenic mycoplasmas. On the other hand, they are host-specific pathogens with some highly pathogenic members that can colonize a vast number of habitats. Reshuffling mycoplasmas genetic information and evolving rapidly is a way to avoid their host's immune system. However, currently, only a few control measures exist against some mycoplasmosis which are far from satisfaction. This review aimed to provide an updated insight into the state of mycoplasmas as pathogens by summarizing and analyzing the comprehensive progress, current challenge, and future perspectives of mycoplasmas. It covers clinical implications of mycoplasmas in humans and domestic and wild animals, virulence-related factors, the process of gene transfer and its crucial prospects, the current application and future perspectives of nanotechnology for diagnosing and curing mycoplasmosis, Mycoplasma vaccination, and protective immunity. Several questions remain unanswered and are recommended to pay close attention to. The findings would be helpful to develop new strategies for basic and applied research on mycoplasmas and facilitate the control of mycoplasmosis for humans and various species of animals.
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Affiliation(s)
- Ali Dawood
- The State Key Laboratory of Agricultural Microbiology, (HZAU), Wuhan, China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, University of Sadat City, Sadat City, Egypt
- Hubei Hongshan Laboratory, Wuhan, China
| | - Samah Attia Algharib
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, HZAU, Wuhan, China
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Benha University, Toukh, Egypt
| | - Gang Zhao
- The State Key Laboratory of Agricultural Microbiology, (HZAU), Wuhan, China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- Hubei Hongshan Laboratory, Wuhan, China
- Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan, China
| | - Tingting Zhu
- The State Key Laboratory of Agricultural Microbiology, (HZAU), Wuhan, China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- Hubei Hongshan Laboratory, Wuhan, China
- Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan, China
| | - Mingpu Qi
- The State Key Laboratory of Agricultural Microbiology, (HZAU), Wuhan, China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- Hubei Hongshan Laboratory, Wuhan, China
- Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan, China
| | - Kong Delai
- The State Key Laboratory of Agricultural Microbiology, (HZAU), Wuhan, China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
| | - Zhiyu Hao
- The State Key Laboratory of Agricultural Microbiology, (HZAU), Wuhan, China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- Hubei Hongshan Laboratory, Wuhan, China
- Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan, China
| | - Marawan A. Marawan
- The State Key Laboratory of Agricultural Microbiology, (HZAU), Wuhan, China
- Infectious Diseases, Faculty of Veterinary Medicine, Benha University, Toukh, Egypt
| | - Ihsanullah Shirani
- The State Key Laboratory of Agricultural Microbiology, (HZAU), Wuhan, China
- Para-Clinic Department, Faculty of Veterinary Medicine, Jalalabad, Afghanistan
| | - Aizhen Guo
- The State Key Laboratory of Agricultural Microbiology, (HZAU), Wuhan, China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
- Hubei Hongshan Laboratory, Wuhan, China
- Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan, China
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31
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Association of antibiotic-consumption patterns with the prevalence of hematological malignancies in European countries. Sci Rep 2022; 12:7821. [PMID: 35550556 PMCID: PMC9098430 DOI: 10.1038/s41598-022-11569-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 04/25/2022] [Indexed: 11/17/2022] Open
Abstract
Hematological malignancies are considered the fifth most common cancer in the world. Several risk factors and probable etiological agents have been suspected in the pathomechanism of those malignancies as infections, chemicals, irradiation, etc., and recently, the contribution of the altered gut flora, dysbiosis, was identified also as a possible additional factor to the existing ones. Host, and external factors, like antibiotics, which were identified as a major disruptor of the "normal" gut flora, influence the composition of the microbiome. Considering the several-fold differences in antibiotic consumption patterns and the incidence of hematological malignancies in European countries, the hypothesis was raised that the dominant consumption of certain antibiotic classes might influence the incidence of different hematological malignancies through the modification of gut flora. Comparisons were performed between the average antibiotic consumption databases reported yearly by ECDC (2009–2019) and the incidence rate of Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and leukemia (LEU) estimated for 2020 in 30 European countries. Applying Spearman calculations, significant positive correlation has been found between the incidence of HL and tetracycline (J01A) consumption (r = 0.399, p = 0.029), NHL and narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.580, p = 0.001), MM and tetracycline (r = 0.492, p = 0.006), penicillin (J01C) (r = 0.366, p = 0.047), narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.574, p = 0.001), while strong, significant negative correlation has been recorded between NHL and cephalosporin (r = − 0.460, p = 0.011), and quinolone (r = − 0.380, p = 0.038). The incidence of LEU did not show any positive or negative association with any antibiotic classes using Spearman calculation. Multivariate ordinal logistic regression (OR) indicated increased risk between HL and the total consumption of systemic antibiotics (J01 p: 0.038), and tetracyclin (J01A p: 0.002). Similarly, increased risk has been detected between the MM and tetracyclin (J01A p: 0.02), and narrow spectrum, beta-lactamase resistant penicillin (J01CF p: 0.042) and decreased risk between cephalosporin and MM (J01D p:0.022). LEU showed increased risk with the consumption of macrolides (p: 0.047).
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32
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The interplay between anticancer challenges and the microbial communities from the gut. Eur J Clin Microbiol Infect Dis 2022; 41:691-711. [PMID: 35353280 DOI: 10.1007/s10096-022-04435-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 03/15/2022] [Indexed: 11/03/2022]
Abstract
Cancer being an increasing burden on human health, the use of anticancer drugs has risen over the last decades. The physiological effects of these drugs are not only perceived by the host's cells but also by the microbial cells it harbors as commensals, notably the gut microbiota. Since the early '50 s, the cytotoxicity of anticancer chemotherapy was evaluated on bacteria revealing some antimicrobial activities that result in an established perturbation of the gut microbiota. This perturbation can affect the host's health through dysbiosis, which can lead to multiple complications, but has also been shown to have a direct effect on the treatment efficiency.We, therefore, conducted a review of literature focusing on this triangular relationship involving the microbial communities from the gut, the host's disease, and the anticancer treatment. We focused specifically on the antimicrobial effects of anticancer chemotherapy, their impact on mutagenesis in bacteria, and the perspectives of using bacteria-based tools to help in the diagnostic and treatment of cancer.
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33
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Anesi A, Berding K, Clarke G, Stanton C, Cryan JF, Caplice N, Ross RP, Doolan A, Vrhovsek U, Mattivi F. Metabolomic Workflow for the Accurate and High-Throughput Exploration of the Pathways of Tryptophan, Tyrosine, Phenylalanine, and Branched-Chain Amino Acids in Human Biofluids. J Proteome Res 2022; 21:1262-1275. [PMID: 35380444 PMCID: PMC9087329 DOI: 10.1021/acs.jproteome.1c00946] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The modulation of host and dietary metabolites by gut microbiota (GM) is important for maintaining correct host physiology and in the onset of various pathologies. An ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the targeted quantitation in human plasma, serum, and urine of 89 metabolites resulting from human-GM cometabolism of dietary essential amino acids tryptophan, tyrosine, and phenylalanine as well as branched-chain amino acids. Ninety-six-well plate hybrid-SPE enables fast clean-up of plasma and serum. Urine was diluted and filtered. A 15 min cycle enabled the acquisition of 96 samples per day, with most of the metabolites stable in aqueous solution for up to 72 h. Calibration curves were specifically optimized to cover expected concentrations in biological fluids, and limits of detection were at the order of ppb. Matrix effects were in acceptable ranges, and analytical recoveries were in general greater than 80%. Inter and intraday precision and accuracy were satisfactory. We demonstrated its application in plasma and urine samples obtained from the same individual in the frame of an interventional study, allowing the quantitation of 51 metabolites. The method could be considered the reference for deciphering changes in human-gut microbial cometabolism in health and disease. Data are available via Metabolights with the identifier MTBLS4399.
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Affiliation(s)
- Andrea Anesi
- Unit of Metabolomics, Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), 38010 San Michele all'Adige, Italy
| | - Kirsten Berding
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland.,Department of Psychiatry and Neurobehavioural Sciences, University College Cork, T12 YT20 Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland
| | - John F Cryan
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland.,Department of Anatomy and Neuroscience, University College Cork, T12 YT20 Cork, Ireland
| | - Noel Caplice
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland.,Centre for Research in Vascular Biology, University College Cork, T12 YT20 Cork, Ireland
| | - R Paul Ross
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland
| | - Andrea Doolan
- Atlantia Food Clinical Trial, Blackpool, T23 R50R Cork, Ireland
| | - Urska Vrhovsek
- Unit of Metabolomics, Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), 38010 San Michele all'Adige, Italy
| | - Fulvio Mattivi
- Unit of Metabolomics, Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach (FEM), 38010 San Michele all'Adige, Italy.,Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy
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van den Boom A, Lavrijssen B, Fest J, Ikram M, Stricker B, van Eijck C, Ruiter R. Appendectomy and the subsequent risk of cancer: A prospective population-based cohort study with long follow-up. Cancer Epidemiol 2022; 77:102120. [PMID: 35228019 DOI: 10.1016/j.canep.2022.102120] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 01/17/2022] [Accepted: 02/04/2022] [Indexed: 11/27/2022]
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35
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Nayak DA, Binder RJ. Agents of cancer immunosurveillance: HSPs and dsDNA. Trends Immunol 2022; 43:404-413. [PMID: 35382994 PMCID: PMC9058224 DOI: 10.1016/j.it.2022.03.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/07/2022] [Accepted: 03/08/2022] [Indexed: 10/18/2022]
Abstract
Tumor immunosurveillance requires tumor cell-derived molecules to initiate responses through corresponding receptors on antigen presenting cells (APCs) and a specific effector response designed to eliminate the emerging tumor cells. This is supported by evidence from immunodeficient individuals and experimental animals. Recent discoveries suggest that adjuvanticity of tumor-derived heat shock proteins (HSPs) and double-stranded DNA (dsDNA) are necessary for tumor-specific immunity. There is also the obligatory early transfer of tumor antigens to APCs. We argue that tumor-derived HSPs deliver sufficient chaperoned antigen for cross-priming within the quantitative limits set by nascent tumors. In contrast to late-stage tumors, we are only just beginning to understand the unique interactions of the immune system with precancerous/nascent neoplastic cells, which is important for improved cancer prevention measures.
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36
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Moschen AR, Sammy Y, Marjenberg Z, Heptinstall AB, Pooley N, Marczewska AM. The Underestimated and Overlooked Burden of Diarrhea and Constipation in Cancer Patients. Curr Oncol Rep 2022; 24:861-874. [PMID: 35325401 DOI: 10.1007/s11912-022-01267-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2022] [Indexed: 12/12/2022]
Abstract
PURPOSE OF REVIEW This review aims to summarize and discuss the diverse causes of two major gastrointestinal dysfunction symptoms, diarrhea and constipation, in cancer patients. We also discuss short- and long-term clinical, economic, and humanistic consequences, including the impact on cancer treatment regimens and patient quality of life, highlighting the limitations of the literature. RECENT FINDINGS Diarrhea and constipation as a result of cancer and its treatment can risk the success of anti-cancer therapies by requiring treatment delay or withdrawal, and imposes a substantial humanistic burden in patients with cancer. Despite its importance and frequency, gastrointestinal side effects may be overlooked due to the focus on cancer treatment, and the impact on patients may be underestimated. Additionally, the burden reported may not fully reflect current cancer management, particularly the true impact of economic consequences. A full understanding of the burden of diarrhea and constipation in patients with cancer is required, including broad evaluation of clinical considerations, the patient experience, and an updated assessment of economic burden. This would improve caregivers' appreciation of the impact of gastrointestinal dysfunction and aid the prioritization of future research efforts.
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Feng Z, Hu Y, Wang X, Li Y, Yu Y, He J, Li H, Zhang T, Zhang L, Shen G, Ding X. In situ imaging for tumor microbiome interactions via imaging mass cytometry on single-cell level. Cytometry A 2022; 101:617-629. [PMID: 35301803 DOI: 10.1002/cyto.a.24550] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 01/13/2022] [Accepted: 03/15/2022] [Indexed: 11/12/2022]
Abstract
Co-detection of multiplex cancer subtypes and bacteria subtypes in situ is crucial for understanding tumor microbiome interactions in tumor microenvironment. Current standard techniques such as immunohistochemical staining and immunofluorescence staining are limited for their multiplicity. Simultaneously visualizing detailed cell subtypes and bacteria distribution across the same pathological section remains a major technical challenge. Herein, we developed a rapid semi-quantitative method for in situ imaging of bacteria and multiplex cell phenotypes on the same solid tumor tissue sections. We designed a panel of antibody probes labeled with mass tags, namely prokaryotic and eukaryotic cell hybrid probes for in situ imaging (PEHPSI). For application demonstration, PEHPSI stained two bacteria subtypes (lipopolysaccharides (LPS) for Gram-negative bacteria and lipoteichoic acid (LTA) for Gram-positive bacteria) simultaneously with four types of immune cells (leukocytes, CD8+T-cells, B-cells and macrophages) and four breast cancer subtypes (classified by a panel of 12 human proteins) on the same tissue section. We unveiled that breast cancer cells are commonly enriched with Gram-negative bacteria and almost absent of Gram-positive bacteria, regardless of the cancer subtypes (triple-negative breast cancer (TNBC), HER2+, Luminal A and Luminal B). Further analysis revealed that on the single-cell level, Gram-negative bacteria have a significant correlation with CD8+T-cells only in HER2+ breast cancer, while PKCD, ER, PR and Ki67 are correlated with Gram-negative bacteria in the other three subtypes of breast cancers. On the cell population level, in TNBC, CD19 expression intensity is up-regulated by approximately 25% in bacteria-enriched cells, while for HER2+, Luminal A and Luminal B breast cancers, the intensity of biomarkers associated with the malignancy, metastasis and proliferation of cancer cells (PKCD, ISG15 and IFI6) is down-regulated by 29-38%. The flexible and expandable PEHPSI system permits intuitive multiplex co-visualization of bacteria and mammalian cells, which facilitates future research on tumor microbiome and tumor pathogenesis. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Zijian Feng
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Yuli Hu
- Department of Pathology, Wenling First People's Hospital, Wenling City, China
| | - Xin Wang
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Yiyang Li
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Youyi Yu
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Jie He
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Hongxia Li
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Ting Zhang
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Lulu Zhang
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Guangxia Shen
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Xianting Ding
- Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
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Rana D, Salave S, Perla A, Nadkarni A, Kohle S, Jindal AB, Mandoli A, Dwivedi P, Benival D. Bugs as Drugs: Understanding the Linkage between Gut Microbiota and Cancer Treatment Microbiome in Cancer Therapy. Curr Drug Targets 2022; 23:869-888. [PMID: 35264088 DOI: 10.2174/1389450123666220309101345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/03/2022] [Accepted: 01/12/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND The commensal microbiota is known to regulate host physiology. Dysbiosis or compromised Resilience in the microbial ecology is related to the impending risk of cancer. A potential link between cancer and microbiota is indicated by a lot of evidence. OBJECTIVE The current review explores in detail the various links leading to and /or facilitating oncogenesis, providing sound reasoning or a basis for its utilization as potential therapeutic targets. The present review emphasizes the existing knowledge of the microbiome in cancer and further elaborates on the factors like genetic modifications, effects of dietary components, and environmental agents that are considered to assess the direct and indirect effect of microbes in the process of oncogenesis and on the host's health. Strategies modulating the microbiome and novel biotherapeutics are also discussed. Pharmacomicrobiomics is one such niche accounting for the interplay between the microbiome, xenobiotic, and host responses is also looked upon. METHODS The literature search strategy for this review was conducted by following the methodology of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The method includes the collection of data from different search engines like PubMed, ScienceDirect, SciFinder etc. to get coverage of relevant literature for accumulating appropriate information regarding microbiome, cancer, and their linkages. RESULTS These considerations are made to expand the existing literature on the role of gut microbiota on the host's health, the interaction between host and microbiota, and the reciprocal relationship between the microbiome and modified neoplastic cells. CONCLUSION Potential therapeutic implications of cancer microbiomes that are yet unexplored and have rich therapeutic dividends improving human health are discussed in detail in this review.
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Affiliation(s)
- Dhwani Rana
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Sagar Salave
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Akhil Perla
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Akanksha Nadkarni
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Shital Kohle
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Anil B Jindal
- Department of Pharmacy, Birla Institute of Technology and Science Pilani (BITS PILANI), Pilani Campus, Rajasthan, 333031, India
| | - Amit Mandoli
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
| | - Pradeep Dwivedi
- Department of Pharmacology, All India Institute of Medical Sciences- Jodhpur (AIIMS), 342005, India
| | - Derajram Benival
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A), 382355, India
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Health Benefits of Apple Juice Consumption: A Review of Interventional Trials on Humans. Nutrients 2022; 14:nu14040821. [PMID: 35215471 PMCID: PMC8879758 DOI: 10.3390/nu14040821] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 12/12/2022] Open
Abstract
Although numerous studies have reported the benefits of apple consumption on cardiometabolic health parameters and chronic disease prevention, few have focused on the effects of apple juice specifically. Juice consumption may be a convenient way to take advantage of the health effects of the bioactive components present in apples. The present review aims to summarize the current literature on health benefits of apple juice as reported in clinical trials in humans. Of the 67 studies retained, 20 interventional studies on humans were reviewed. Overall, cloudy apple juice consumption was found to be associated with several markers of cardiovascular health that may ultimately be relevant for cancer and neurodegenerative diseases. Most of the documentation was found regarding oxidative stress, as well as observations with other parameters such as markers of inflammation, lipid profile, and diabetes. This review suggests that, in 20 studies, apple juice consumed in moderation exerts positive effects on markers of cardiovascular disease risk (particularly on oxidative stress).
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Doocey CM, Finn K, Murphy C, Guinane CM. The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development. BMC Microbiol 2022; 22:53. [PMID: 35151278 PMCID: PMC8840051 DOI: 10.1186/s12866-022-02465-6] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 02/03/2022] [Indexed: 02/08/2023] Open
Abstract
Abstract
Background
Cancer impacts millions of lives globally each year, with approximately 10 million cancer-related deaths recorded worldwide in 2020. Mounting research has recognised the human microbiome as a key area of interest in the pathophysiology of various human diseases including cancer tumorigenesis, progression and in disease outcome. It is suggested that approximately 20% of human cancers may be linked to microbes. Certain residents of the human microbiome have been identified as potentially playing a role, including: Helicobacter pylori, Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Porphyromonas gingivalis.
Main body
In this review, we explore the current evidence that indicate a link between the human microbiome and cancer. Microbiome compositional changes have been well documented in cancer patients. Furthermore, pathogenic microbes harbouring specific virulence factors have been implicated in driving the carcinogenic activity of various malignancies including colorectal, gastric and pancreatic cancer. The associated genetic mechanisms with possible roles in cancer will be outlined. It will be indicated which microbes have a potential direct link with cancer cell proliferation, tumorigenesis and disease progression. Recent studies have also linked certain microbial cytotoxins and probiotic strains to cancer cell death, suggesting their potential to target the tumour microenvironment given that cancer cells are integral to its composition. Studies pertaining to such cytotoxic activity have suggested the benefit of microbial therapies in oncological treatment regimes. It is also apparent that bacterial pathogenic protein products encoded for by certain loci may have potential as oncogenic therapeutic targets given their possible role in tumorigenesis.
Conclusion
Research investigating the impact of the human microbiome in cancer has recently gathered pace. Vast amounts of evidence indicate the human microbiome as a potential player in tumorigenesis and progression. Promise in the development of cancer biomarkers and in targeted oncological therapies has also been demonstrated, although more studies are needed. Despite extensive in vitro and in vivo research, clinical studies involving large cohorts of human patients are lacking. The current literature suggests that further intensive research is necessary to validate both the role of the human microbiome in cancer, and the use of microbiome modification in cancer therapy.
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Chu CS, Yang CY, Yeh CC, Lin RT, Chen CC, Bai LY, Hung MC, Lin CC, Wu CY, Lin JT. Endoscopic ultrasound-guided fine-needle biopsy as a tool for studying the intra-tumoral microbiome in pancreatic ductal adenocarcinoma: a pilot study. Sci Rep 2022; 12:107. [PMID: 34997106 PMCID: PMC8741880 DOI: 10.1038/s41598-021-04095-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Accepted: 12/15/2021] [Indexed: 12/04/2022] Open
Abstract
A new approach by investigating the intra-tumoral microbiome raised great interest because they may influence the host immune response and natural history of the disease. However, previous studies on the intra-tumoral microbiome of pancreatic ductal adenocarcinoma (PDAC) were mostly based on examining the formalin-fixed paraffin-embedded tumor specimens. This study aims to investigate the feasibility of using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) as a complementary procedure of surgical biopsy to obtain adequate fresh pancreatic cancer tissue for intra-tumoral microbial research. This was a prospective pilot study performed at a single tertiary referral center. We obtained pancreatic cancer tissue by EUS-FNB and surgical biopsy, respectively. We amplified the V3-V4 hyper-variable region of bacterial 16S ribosomal ribonucleic acid (rRNA) genes, constructed a pair-end library, and performed high-throughput sequencing. From August 2020 to November 2020, nine eligible patients with PDAC were enrolled in this study. The intra-tumoral microbiome profile was successfully generated from the PDAC cancer tissue obtained by EUS-FNB as well as by surgical biopsy. There was no significant difference in intra-tumoral alpha-diversity or bacterial taxonomic composition between tissues obtained by EUS-FNB and by surgical biopsy. EUS-FNB can collect sufficient fresh cancer tissue for microbiome analyses without complication. The intra-tumoral microbiome profile in tissues obtained by EUS-FNB had similar alpha-diversity and taxonomic profiles with those obtained by surgical biopsy. It implicated, except for surgical biopsy, EUS-FNB can be another valid and valuable tool for studying intra-tumoral microbiome in patients with resectable and unresectable PDAC.
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Affiliation(s)
- Chia-Sheng Chu
- Digestive Medicine Center, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan
| | - Chi-Ying Yang
- Digestive Medicine Center, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan
| | - Chun-Chieh Yeh
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Ro-Ting Lin
- College of Public Health, China Medical University, Taichung, Taiwan
| | - Chi-Ching Chen
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Li-Yuan Bai
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
| | - Mien-Chie Hung
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.,The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Chun-Che Lin
- Digestive Medicine Center, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan.,School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
| | - Chun-Ying Wu
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jaw-Town Lin
- Digestive Medicine Center, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan.
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D'Amico F, Barone M, Tavella T, Rampelli S, Brigidi P, Turroni S. Host microbiomes in tumor precision medicine: how far are we? Curr Med Chem 2022; 29:3202-3230. [PMID: 34986765 DOI: 10.2174/0929867329666220105121754] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/13/2021] [Accepted: 11/22/2021] [Indexed: 11/22/2022]
Abstract
The human gut microbiome has received a crescendo of attention in recent years, due to the countless influences on human pathophysiology, including cancer. Research on cancer and anticancer therapy is constantly looking for new hints to improve the response to therapy while reducing the risk of relapse. In this scenario, the gut microbiome and the plethora of microbial-derived metabolites are considered a new opening in the development of innovative anticancer treatments for a better prognosis. This narrative review summarizes the current knowledge on the role of the gut microbiome in the onset and progression of cancer, as well as in response to chemo-immunotherapy. Recent findings regarding the tumor microbiome and its implications for clinical practice are also commented on. Current microbiome-based intervention strategies (i.e., prebiotics, probiotics, live biotherapeutics and fecal microbiota transplantation) are then discussed, along with key shortcomings, including a lack of long-term safety information in patients who are already severely compromised by standard treatments. The implementation of bioinformatic tools applied to microbiomics and other omics data, such as machine learning, has an enormous potential to push research in the field, enabling the prediction of health risk and therapeutic outcomes, for a truly personalized precision medicine.
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Affiliation(s)
- Federica D'Amico
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Monica Barone
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Teresa Tavella
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Simone Rampelli
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | - Patrizia Brigidi
- Microbiome Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna 40138, Italy
| | - Silvia Turroni
- Unit of Microbiome Science and Biotechnology, Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
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Orendain-Jaime EN, Serafín-Higuera N, Leija-Montoya AG, Martínez-Coronilla G, Moreno-Trujillo M, Sánchez-Muñoz F, Ruiz-Hernández A, González-Ramírez J. MicroRNAs Encoded by Virus and Small RNAs Encoded by Bacteria Associated with Oncogenic Processes. Processes (Basel) 2021; 9:2234. [DOI: 10.3390/pr9122234] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Cancer is a deadly disease and, globally, represents the second leading cause of death in the world. Although it is a disease where several factors can help its development, virus induced infections have been associated with different types of neoplasms. However, in bacterial infections, their participation is not known for certain. Among the proposed approaches to oncogenesis risks in different infections are microRNAs (miRNAs). These are small molecules composed of RNA with a length of 22 nucleotides capable of regulating gene expression by directing protein complexes that suppress the untranslated region of mRNA. These miRNAs and other recently described, such as small RNAs (sRNAs), are deregulated in the development of cancer, becoming promising biomarkers. Thus, resulting in a study possibility, searching for new tools with diagnostic and therapeutic approaches to multiple oncological diseases, as miRNAs and sRNAs are main players of gene expression and host–infectious agent interaction. Moreover, sRNAs with limited complementarity are similar to eukaryotic miRNAs in their ability to modulate the activity and stability of multiple mRNAs. Here, we will describe the regulatory RNAs from viruses that have been associated with cancer and how sRNAs in bacteria can be related to this disease.
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Affiliation(s)
- Erika Nallely Orendain-Jaime
- Facultad de Enfermería, Universidad Autónoma de Baja California, Av. Álvaro Obregón y Calle “G” S/N, Col. Nueva, Mexicali 21100, BC, Mexico
| | - Nicolás Serafín-Higuera
- Facultad de Odontología, Universidad Autónoma de Baja California, Zotoluca s/n, Fracc. Calafia, Mexicali 21040, BC, Mexico
| | - Ana Gabriela Leija-Montoya
- Facultad de Medicina Mexicali, Universidad Autónoma de Baja California, Centro Cívico, Mexicali 21000, BC, Mexico
| | - Gustavo Martínez-Coronilla
- Facultad de Medicina Mexicali, Universidad Autónoma de Baja California, Centro Cívico, Mexicali 21000, BC, Mexico
| | - Misael Moreno-Trujillo
- Departamento de Cuidados Intensivos, Hospital de Gineco-Pediatría #31, Instituto Mexicano del Seguro Social, Av. Sebastián Lerdo de Tejada S/N, Col. Nueva, Mexicali 21100, BC, Mexico
| | - Fausto Sánchez-Muñoz
- Departamento de Inmunología, Instituto Nacional de Cardiología, Juan Badiano No. 1, Col. Sección XVI, Tlalpan 140080, DF, Mexico
| | - Armando Ruiz-Hernández
- Facultad de Medicina Mexicali, Universidad Autónoma de Baja California, Centro Cívico, Mexicali 21000, BC, Mexico
| | - Javier González-Ramírez
- Facultad de Enfermería, Universidad Autónoma de Baja California, Av. Álvaro Obregón y Calle “G” S/N, Col. Nueva, Mexicali 21100, BC, Mexico
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Devlin SM, Martin A, Ostrovnaya I. Identifying prognostic pairwise relationships among bacterial species in microbiome studies. PLoS Comput Biol 2021; 17:e1009501. [PMID: 34752448 PMCID: PMC8631663 DOI: 10.1371/journal.pcbi.1009501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 11/30/2021] [Accepted: 09/28/2021] [Indexed: 11/18/2022] Open
Abstract
In recent literature, the human microbiome has been shown to have a major influence on human health. To investigate this impact, scientists study the composition and abundance of bacterial species, commonly using 16S rRNA gene sequencing, among patients with and without a disease or condition. Methods for such investigations to date have focused on the association between individual bacterium and an outcome, and higher-order pairwise relationships or interactions among bacteria are often avoided due to the substantial increase in dimension and the potential for spurious correlations. However, overlooking such relationships ignores the environment of the microbiome, where there is dynamic cooperation and competition among bacteria. We present a method for identifying and ranking pairs of bacteria that have a differential dichotomized relationship across outcomes. Our approach, implemented in an R package PairSeek, uses the stability selection framework with data-driven dichotomized forms of the pairwise relationships. We illustrate the properties of the proposed method using a published oral cancer data set and a simulation study. Within an ecological system, microbial communities represent complex relationships between bacteria, where they co-exist and interact with each other in multiple ways including cooperation and competition. Most existing statistical tools for examining the association between microbiota and a disease state, such as individuals with and without cancer, focus on individual bacterium in isolation, ignoring the dynamic environment in which it lives. In this manuscript, we propose an algorithm for assessing the association between pairs of bacteria and a disease state. The approach provides a mechanism to rank pairs of bacteria, from pairs with the most evidence of an association with the disease state to the least amount of evidence. This ranking helps generate hypotheses and prioritize bacteria for further investigation. We illustrate the algorithm using a publicly available data set of oral cancer patients.
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Affiliation(s)
- Sean M Devlin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States of America
| | - Axel Martin
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States of America
| | - Irina Ostrovnaya
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, United States of America
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Wertman JN, Dunn KA, Kulkarni K. The impact of the host intestinal microbiome on carcinogenesis and the response to chemotherapy. Future Oncol 2021; 17:4371-4387. [PMID: 34448411 DOI: 10.2217/fon-2021-0087] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The microbiome consists of all microbes present on and within the human body. An unbalanced, or 'dysbiotic' intestinal microbiome is associated with inflammatory bowel disease, diabetes and some cancer types. Drug treatment can alter the intestinal microbiome composition. Additionally, some chemotherapeutics interact with microbiome components, leading to changes in drug safety and/or efficacy. The intestinal microbiome is a modifiable target, using strategies such as antibiotic treatment, fecal microbial transplantation or probiotic administration. Understanding the impact of the microbiome on the safety and efficacy of cancer treatment may result in improved treatment outcome. The present review seeks to summarize relevant research and look to the future of cancer treatment, where the intestinal microbiome is recognized as an actionable treatment target.
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Affiliation(s)
- Jaime N Wertman
- Department of Pediatrics/Division of Pediatric Hematology-Oncology, Dalhousie University/IWK Health Centre, Halifax, Canada
- College of Pharmacy, Dalhousie University, Halifax, Canada
| | - Katherine A Dunn
- Department of Pediatrics/Division of Pediatric Hematology-Oncology, Dalhousie University/IWK Health Centre, Halifax, Canada
- Department of Biology, Dalhousie University, Halifax, Canada
| | - Ketan Kulkarni
- Department of Pediatrics/Division of Pediatric Hematology-Oncology, Dalhousie University/IWK Health Centre, Halifax, Canada
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Lee K, Oh HJ, Kang MS, Kim S, Ahn S, Kim MJ, Kim SW, Chang S. Metagenomic analysis of gut microbiome reveals a dynamic change in Alistipes onderdonkii in the preclinical model of pancreatic cancer, suppressing its proliferation. Appl Microbiol Biotechnol 2021; 105:8343-8358. [PMID: 34648062 DOI: 10.1007/s00253-021-11617-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 09/12/2021] [Accepted: 09/20/2021] [Indexed: 12/13/2022]
Abstract
Pancreatic cancer is a lethal cancer with aggressive and invasive characteristics. By the time it is diagnosed, patients already have tumors extended to other organs and show extremely low survival rates. The gut microbiome is known to be associated with many diseases and its imbalance affects the pathogenesis of pancreatic cancer. In this study, we established an orthotopic, patient-derived xenograft model to identify how the gut microbiome is linked to pancreatic ductal adenocarcinoma (PDAC). Using the 16S rDNA metagenomic sequencing, we revealed that the levels of Alistipes onderdonkii and Roseburia hominis decreased in the gut microbiome of the PDAC model. To explore the crosstalk between the two bacteria and PDAC cells, we collected the supernatant of the bacteria or cancer cell culture medium and treated it in a cross manner. While the cancer cell medium did not affect bacterial growth, we observed that the A. onderdonkii medium suppressed the growth of the pancreatic primary cancer cells. Using the bromodeoxyuridine/7-amino-actinomycin D (BrdU/7-AAD) staining assay, we confirmed that the A. onderdonkii medium inhibited the proliferation of the pancreatic primary cancer cells. Furthermore, RNA-seq analysis revealed that the A. onderdonkii medium induced unique transcriptomic alterations in the PDAC cells, compared to the normal pancreatic cells. Altogether, our data suggest that the reduction in the A. onderdonkii in the gut microbiome provides a proliferation advantage to the pancreatic cancer cells. KEY POINTS: • Metagenome analysis of pancreatic cancer model reveals A. onderdonkii downregulation. • A. onderdonkii culture supernatant suppressed the proliferation of pancreatic cancer cells. • RNA seq data reveals typical gene expression changes induced by A. onderdonkii.
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Affiliation(s)
- Kihak Lee
- Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Hyo Jae Oh
- Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Min-Su Kang
- Division of Applied Life Science (BK21 Four), PMBBRC, Gyeongsang National University, Jinju, Republic of Korea
| | - Sinae Kim
- Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Sehee Ahn
- Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Myung Ji Kim
- Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea
| | - Seon-Won Kim
- Division of Applied Life Science (BK21 Four), PMBBRC, Gyeongsang National University, Jinju, Republic of Korea.
| | - Suhwan Chang
- Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea.
- Department of Physiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Republic of Korea.
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Nardelli C, Granata I, Nunziato M, Setaro M, Carbone F, Zulli C, Pilone V, Capoluongo ED, De Palma GD, Corcione F, Matarese G, Salvatore F, Sacchetti L. 16S rRNA of Mucosal Colon Microbiome and CCL2 Circulating Levels Are Potential Biomarkers in Colorectal Cancer. Int J Mol Sci 2021; 22:10747. [PMID: 34639088 PMCID: PMC8509685 DOI: 10.3390/ijms221910747] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/30/2021] [Accepted: 09/30/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignancies in the Western world and intestinal dysbiosis might contribute to its pathogenesis. The mucosal colon microbiome and C-C motif chemokine 2 (CCL2) were investigated in 20 healthy controls (HC) and 20 CRC patients using 16S rRNA sequencing and immunoluminescent assay, respectively. A total of 10 HC subjects were classified as overweight/obese (OW/OB_HC) and 10 subjects were normal weight (NW_HC); 15 CRC patients were classified as OW/OB_CRC and 5 patients were NW_CRC. Results: Fusobacterium nucleatum and Escherichia coli were more abundant in OW/OB_HC than in NW_HC microbiomes. Globally, Streptococcus intermedius, Gemella haemolysans, Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were significantly increased in CRC patient tumor/lesioned tissue (CRC_LT) and CRC patient unlesioned tissue (CRC_ULT) microbiomes compared to HC microbiomes. CCL2 circulating levels were associated with tumor presence and with the abundance of Fusobacterium nucleatum, Bacteroides fragilis and Gemella haemolysans. Our data suggest that mucosal colon dysbiosis might contribute to CRC pathogenesis by inducing inflammation. Notably, Fusobacterium nucleatum, which was more abundant in the OW/OB_HC than in the NW_HC microbiomes, might represent a putative link between obesity and increased CRC risk.
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Affiliation(s)
- Carmela Nardelli
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy; (C.N.); (M.N.); (E.D.C.); (G.M.); (F.S.)
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
- Task Force on Microbiome Studies, University of Naples Federico II, 80131 Naples, Italy
| | - Ilaria Granata
- Institute for High Performance Computing and Networking (ICAR), National Research Council (CNR), 80131 Naples, Italy;
| | - Marcella Nunziato
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy; (C.N.); (M.N.); (E.D.C.); (G.M.); (F.S.)
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
| | - Mario Setaro
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
| | - Fortunata Carbone
- Laboratory of Immunology, Institute of Endocrinology and Experimental Oncology, Consiglio Nazionale Delle Ricerche (IEOS-CNR), 80131 Naples, Italy;
- Neuroimmunology Unit, IRCCS Fondazione Santa Lucia, 00143 Roma, Italy
| | - Claudio Zulli
- Digestive Endoscopy Unit, Gaetano Fucito Hospital, Mercato San Severino, 84085 Salerno, Italy;
| | - Vincenzo Pilone
- Department of Medicine and Surgery, AOU San Giovanni di Dio e Ruggi D’Aragona, University of Salerno, 84084 Salerno, Italy;
| | - Ettore Domenico Capoluongo
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy; (C.N.); (M.N.); (E.D.C.); (G.M.); (F.S.)
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
| | - Giovanni Domenico De Palma
- Department Clinical Medicine and Surgery, Federico II University of Naples, Via Pansini 5, 80131 Naples, Italy;
| | - Francesco Corcione
- Department of Public Health, School of Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy;
| | - Giuseppe Matarese
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy; (C.N.); (M.N.); (E.D.C.); (G.M.); (F.S.)
- Laboratory of Immunology, Institute of Endocrinology and Experimental Oncology, Consiglio Nazionale Delle Ricerche (IEOS-CNR), 80131 Naples, Italy;
| | - Francesco Salvatore
- Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy; (C.N.); (M.N.); (E.D.C.); (G.M.); (F.S.)
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
| | - Lucia Sacchetti
- CEINGE Biotecnologie Avanzate S.C.a R.L., 80131 Naples, Italy;
- Task Force on Microbiome Studies, University of Naples Federico II, 80131 Naples, Italy
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Mamgain G, Patra P, Naithani M, Nath UK. The Role of Microbiota in the Development of Cancer Tumour Cells and Lymphoma of B and T Cells. Cureus 2021; 13:e19047. [PMID: 34853760 PMCID: PMC8608681 DOI: 10.7759/cureus.19047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2021] [Indexed: 11/26/2022] Open
Abstract
Human body harbours enormous numbers of microbial organisms, including bacteria, viruses, and fungi which have a momentous role in well-being and illness in humans. Immune system shelters us from pathogenic bacteria, microorganisms found in human tissues have many benefits related to the functional movement of the host by regulating important procedures such as immunity, signalling, and breakdown. Lymphocytes assume a significant part in the reaction to bacterial colonization, primarily by prompting a safe reaction to obstruction or initiation. Most immunologically occupant cells have a place with the mucosal invulnerable framework and are continually motioned by dendritic cells or other Antigen introducing cells that gather intestinal samples. Thus, Microbiome is a key contributor to developing lymphoma and specific alterations to microbiome composition could attenuate the risk. There is an indication that microbial morphology can affect and control humanoids. The difference in the composition of these microorganisms is associated with tumour development. With the increased knowledge of the connection among the human microbiome and carcinogenesis, the use of these findings to prevent, predict or diagnose of lymphomas has attracted a great attention. In this article, we explored current knowledge of various microbial ecosystems, their connection with carcinogens and the potential for useful microorganisms to control and prevent B and T cell lymphoma.
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Affiliation(s)
- Garima Mamgain
- Medical Oncology and Haematology, All India Institute of Medical Sciences, Rishikesh, IND
| | - Priyanka Patra
- Biochemistry, All India Institute of Medical Sciences, Rishikesh, IND
| | - Manisha Naithani
- Biochemistry & Advanced Center of Continuous Professional Development, All India Institute of Medical Sciences, Rishikesh, IND
| | - Uttam Kumar Nath
- Medical Oncology and Haematology, All India Institute of Medical Sciences, Rishikesh, IND
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49
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Tanaka Y, Shimizu S, Shirotani M, Yorozu K, Kitamura K, Oehorumu M, Kawai Y, Fukuzawa Y. Nutrition and Cancer Risk from the Viewpoint of the Intestinal Microbiome. Nutrients 2021; 13:nu13103326. [PMID: 34684330 PMCID: PMC8541425 DOI: 10.3390/nu13103326] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/08/2021] [Accepted: 09/21/2021] [Indexed: 12/19/2022] Open
Abstract
There are various important factors in reducing the risk of cancer development and progression; these factors may correct an unbalanced intake of nutrients to maintain the living body’s homeostasis, detoxify toxic materials, acting as an external factor, and maintain and strengthen the body’s immune function. In a normal cell environment, nutrients, such as carbohydrates, lipids, proteins, vitamins, and minerals, are properly digested and absorbed into the body, and, as a result, an environment in which cancer can develop and progress is prevented. It is necessary to prevent toxic materials from entering the body and to detoxify poisons in the body. If these processes occur correctly, cells work normally, and genes cannot be damaged. The most important factor in the fight against cancer and prevention of the development and progression of cancer is the immune system. This requires a nutritional state in which the immune system works well, allowing the intestinal microbiome to carry out all of its roles. In order to grow intestinal microbiota, the consumption of prebiotics, such as organic vegetables, fruits, and dietary fiber, and probiotics of effective intestinal microbiota, such as fermented foods and supplements, is required. Symbiosis, in which these organisms work together, is an effective means of reducing the risk of cancer. In addition, fecal microbiota transplantation (FMT) using ultrafine bubble water, produced specially by the Association for Clinical Research of Fecal Microbiota Transplantation Japan, is also useful for improving the nutritional condition and reducing the risk of cancer.
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Affiliation(s)
- Yoshimu Tanaka
- Jinzenkai Tanaka Clinic, 2-3-8, Ikunonishi, Ikuno-ku, Osaka 544-0024, Japan
- The Association for Clinical Research of Fecal Microbiota Transplantation Japan, 2-1-40, Katamachi, Miyakojima-ku, Osaka 534-0025, Japan; (S.S.); (M.S.); (K.Y.); (K.K.); (M.O.); (Y.K.); (Y.F.)
- Correspondence:
| | - Shin Shimizu
- The Association for Clinical Research of Fecal Microbiota Transplantation Japan, 2-1-40, Katamachi, Miyakojima-ku, Osaka 534-0025, Japan; (S.S.); (M.S.); (K.Y.); (K.K.); (M.O.); (Y.K.); (Y.F.)
- Symbiosis Research Institute, 6-7-4-106, Minatojimaminami-machi, Chuo-ku, Kobe, Hyogo 650-0047, Japan
| | - Masahiko Shirotani
- The Association for Clinical Research of Fecal Microbiota Transplantation Japan, 2-1-40, Katamachi, Miyakojima-ku, Osaka 534-0025, Japan; (S.S.); (M.S.); (K.Y.); (K.K.); (M.O.); (Y.K.); (Y.F.)
- Luke’s Ashiya Clinic, 8-2, Ohara-cho, Ashiya, Hyogo 659-0092, Japan
| | - Kensho Yorozu
- The Association for Clinical Research of Fecal Microbiota Transplantation Japan, 2-1-40, Katamachi, Miyakojima-ku, Osaka 534-0025, Japan; (S.S.); (M.S.); (K.Y.); (K.K.); (M.O.); (Y.K.); (Y.F.)
- Ishinkai Yorozu Clinic, 1-118-4, Mihagino, Tottori 689-0202, Japan
| | - Kunihiro Kitamura
- The Association for Clinical Research of Fecal Microbiota Transplantation Japan, 2-1-40, Katamachi, Miyakojima-ku, Osaka 534-0025, Japan; (S.S.); (M.S.); (K.Y.); (K.K.); (M.O.); (Y.K.); (Y.F.)
- Kitamura Clinic, 4-3-8, Nishiki-machi, Onojo, Fukuoka 816-0935, Japan
| | - Masayuki Oehorumu
- The Association for Clinical Research of Fecal Microbiota Transplantation Japan, 2-1-40, Katamachi, Miyakojima-ku, Osaka 534-0025, Japan; (S.S.); (M.S.); (K.Y.); (K.K.); (M.O.); (Y.K.); (Y.F.)
- LIFE Clinic Tateshina, 3317-1, Toyohira, Chino, Nagano 391-0213, Japan
| | - Yuichi Kawai
- The Association for Clinical Research of Fecal Microbiota Transplantation Japan, 2-1-40, Katamachi, Miyakojima-ku, Osaka 534-0025, Japan; (S.S.); (M.S.); (K.Y.); (K.K.); (M.O.); (Y.K.); (Y.F.)
- Yuakai Kawai Clinic for Internal Medicine, 3-7-14, Higashi-Nakahama, Joto-ku, Osaka 536-0023, Japan
| | - Yoshitaka Fukuzawa
- The Association for Clinical Research of Fecal Microbiota Transplantation Japan, 2-1-40, Katamachi, Miyakojima-ku, Osaka 534-0025, Japan; (S.S.); (M.S.); (K.Y.); (K.K.); (M.O.); (Y.K.); (Y.F.)
- Aichi Medical Preemptive and Integrative Medicine Center, Aichi Medical University Hospital, Yazakokarimata, Nagakute, Aichi 480-1103, Japan
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50
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Liu Y, Wang SL, Zhang JF, Zhang W, Zhou S, Li W. DMFMDA: Prediction of Microbe-Disease Associations Based on Deep Matrix Factorization Using Bayesian Personalized Ranking. IEEE/ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 2021; 18:1763-1772. [PMID: 32816678 DOI: 10.1109/tcbb.2020.3018138] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Identifying the microbe-disease associations is conducive to understanding the pathogenesis of disease from the perspective of microbe. In this paper, we propose a deep matrix factorization prediction model (DMFMDA) based on deep neural network. First, the disease one-hot encoding is fed into neural network, which is transformed into a low-dimensional dense vector in implicit semantic space via embedding layer, and so is microbe. Then, matrix factorization is realized by neural network with embedding layer. Furthermore, our model synthesizes the non-linear modeling advantages of multi-layer perceptron based on the linear modeling advantages of matrix factorization. Finally, different from other methods using square error loss function, Bayesian Personalized Ranking optimizes the model from a ranking perspective to obtain the optimal model parameters, which makes full use of the unobserved data. Experiments show that DMFMDA reaches average AUCs of 0.9091 and 0.9103 in the framework of 5-fold cross validation and Leave-one-out cross validation, which is superior to three the-state-of-art methods. In case studies, 10, 9 and 9 out of top-10 candidate microbes are verified by recently published literature for asthma, inflammatory bowel disease and colon cancer, respectively. In conclusion, DMFMDA is successful application of deep learning in the prediction of microbe-disease association.
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