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Gu C, Sha G, Zeng B, Cao H, Cao Y, Tang D. Therapeutic potential of fecal microbiota transplantation in colorectal cancer based on gut microbiota regulation: from pathogenesis to efficacy. Therap Adv Gastroenterol 2025; 18:17562848251327167. [PMID: 40104324 PMCID: PMC11915259 DOI: 10.1177/17562848251327167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 02/24/2025] [Indexed: 03/20/2025] Open
Abstract
Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with its progression intricately linked to gut microbiota dysbiosis. Disruptions in microbial homeostasis contribute to tumor initiation, immune suppression, and inflammation, establishing the microbiota as a key therapeutic target. Fecal microbiota transplantation (FMT) has emerged as a transformative approach to restore microbial balance, enhance immune responses, and reshape the tumor microenvironment. This review explores the mechanisms underlying FMT's therapeutic potential, evaluates its advantages over other microbiota-based interventions, and addresses challenges such as donor selection, safety concerns, and treatment standardization. Looking forward, the integration of FMT into personalized CRC therapies requires robust clinical trials and the identification of predictive biomarkers to optimize its efficacy and safety.
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Affiliation(s)
- Chen Gu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Gengyu Sha
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Binbin Zeng
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Herong Cao
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China
| | - Yibo Cao
- The Second School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Dong Tang
- Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou University, Yangzhou 225000, China
- The Yangzhou Clinical College of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, 221000, China
- Department of General Surgery, Institute of General Surgery, Northern Jiangsu People’s Hospital, Yangzhou University, Yangzhou, 225000, China
- Northern Jiangsu People’s Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Nanjing, 210000, China
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Martin-Quesada AI, Hennessy MA, Gutiérrez AC. Charting cancer's course: revealing the role of diet, exercise, and the microbiome in cancer evolution and immunotherapy response. Clin Transl Oncol 2025; 27:473-485. [PMID: 39095683 PMCID: PMC11782318 DOI: 10.1007/s12094-024-03595-1] [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: 04/08/2024] [Accepted: 07/03/2024] [Indexed: 08/04/2024]
Abstract
A variety of pathophysiological mechanisms exist by which physical exercise, nutrition, and the microbiome can impact the development of cancer and the response of tumor cells to systemic anti-cancer therapy. Physical exercise positively impacts the different stages of oncological disease and may improve overall survival and quality of life, reduce treatment-associated toxicity, and improve response to immunotherapy. Nutrition impacts quality of life, and novel nutritional regimens and their role in cancer treatment and outcomes are under active investigation. Finally, the microbiome may act as a predictor of response and resistance to immunotherapy. This comprehensive review delves into the interplay between these elements and their impact on oncological outcomes, emphasizing their role in modulating the immune system and enhancing the response to immunotherapy.The data that support the findings of this study are openly available and referenced in the bibliography section.
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Affiliation(s)
- Ana Isabel Martin-Quesada
- Cell Therapy and Early Drug Development Unit, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
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Al-Matouq J, Al-Ghafli H, Alibrahim NN, Alsaffar N, Radwan Z, Ali MD. Unveiling the Interplay Between the Human Microbiome and Gastric Cancer: A Review of the Complex Relationships and Therapeutic Avenues. Cancers (Basel) 2025; 17:226. [PMID: 39858007 PMCID: PMC11763844 DOI: 10.3390/cancers17020226] [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: 11/25/2024] [Revised: 12/23/2024] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
The human microbiota plays a crucial role in maintaining overall health and well-being. The gut microbiota has been implicated in developing and progressing various diseases, including cancer. This review highlights the related mechanisms and the compositions that influence cancer pathogenesis with a highlight on gastric cancer. We provide a comprehensive overview of the mechanisms by which the microbiome influences cancer development, progression, and response to treatment, with a focus on identifying potential biomarkers for early detection, prevention strategies, and novel therapeutic interventions that leverage microbiome modulation. This comprehensive review can guide future research and clinical practices in understanding and harnessing the microbiome to optimize gastric cancer therapies.
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Affiliation(s)
- Jenan Al-Matouq
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Hawra Al-Ghafli
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Noura N. Alibrahim
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Nida Alsaffar
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Zaheda Radwan
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Mohammad Daud Ali
- Department of Pharmacy, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia;
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Ma ZS, Li L. Identifications of the potential in-silico biomarkers in lung cancer tissue microbiomes. Comput Biol Med 2024; 183:109231. [PMID: 39432998 DOI: 10.1016/j.compbiomed.2024.109231] [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: 06/23/2024] [Revised: 09/04/2024] [Accepted: 09/28/2024] [Indexed: 10/23/2024]
Abstract
It is postulated that the tumor tissue microbiome is one of the enabling characteristics that can either promote or suppress the ability of tumors to acquire certain hallmarks of cancer. This underscores its critical importance in carcinogenesis, cancer progression, and therapy responses. However, characterizing the tumor microbiomes is extremely challenging because of their low biomass and severe difficulties in controlling laboratory-borne contaminants, which is further aggravated by lack of comprehensively effective computational approaches to identify unique or enriched microbial species associated with cancers. Here we take advantage of a recent computational framework by Ma (2024), termed metagenome comparison (MC) framework (MCF), which can detect treatment-specific, unique or enriched OMUs (operational metagenomic unit), or US/ES (unique/enriched species) when adapted for this study. We apply the MCF to reanalyze four lung cancer tissue microbiome datasets, which include samples from Lung Adenocarcinoma (LUAD), Lung Squamous Cell Carcinoma (LUSC), and their adjacent normal tissue (NT) controls. Our analysis is structured around three distinct schemes: Scheme I-separately detecting the US/ES for each of the four lung cancer microbiome datasets; Scheme II-consolidation of the four datasets followed by detection of US/ES in the combined datasets; Scheme III-construction of the union and intersection sets of US/ES derived from the results of the preceding two schemes. The generated lists of US/ES, including enriched microbial phyla, likely hold significant biomedical value for developing diagnostic and prognostic biomarkers for lung cancer risk assessment, improving the efficacy of immunotherapy, and designing novel microbiome-based therapies in lung cancer research.
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Affiliation(s)
- Zhanshan Sam Ma
- Faculty of Arts and Sciences, Harvard University, Cambridge, MA, 02138, USA; Microbiome Medicine and Advanced AI Lab, Cambridge, MA, 02138, USA; Computational Biology and Medical Ecology Lab, Kunming Institute of Zoology, Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China.
| | - Lianwei Li
- Computational Biology and Medical Ecology Lab, Kunming Institute of Zoology, Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China
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García-Perdomo HA, Granados-Duque V, Spiess PE. What is the relationship between penile cancer and the microbiome? A scoping review. Actas Urol Esp 2024; 48:632-641. [PMID: 38734067 DOI: 10.1016/j.acuroe.2024.05.001] [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: 12/20/2023] [Accepted: 01/17/2024] [Indexed: 05/13/2024]
Abstract
INTRODUCTION The microbiota is defined as the microorganisms in a particular environment. Conversely, the term microbiome is less firmly defined and is used to reference the habitat. OBJECTIVE To identify the association between the microbiome and the penile cancer EVIDENCE ACQUISITION: We performed this scoping review according to the recommendations of the Joanna Briggs Institute. We found five articles that fulfilled the inclusion criteria. We focused on oncogenesis and factors that alter the penile microbiome. We were not limited to language or setting. We searched MEDLINE (Ovid), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and LILACS from inception to the present day. EVIDENCE SYNTHESIS We found nine studies describing multiple factors that could disturb the microbiome, such as sexual behavior, anatomic alterations including circumcision, and inflammatory factors: lichen sclerosus, poor genital hygiene, compromised immune system, smoking, and HPV infection. CONCLUSION Overall, knowledge of the composition of the penile microbiota and its role in penile cancer oncogenesis is minimal. PATIENT SUMMARY Future studies should focus on the relationship between the microbiome and penile cancer to broaden this field of knowledge.
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Affiliation(s)
- H A García-Perdomo
- UROGIV Research Group, Universidad del Valle, Cali, Colombia; Division of Urology/Urooncology, Department of Surgery, School of Medicine, Universidad del Valle, Cali, Colombia.
| | - V Granados-Duque
- UROGIV Research Group, Universidad del Valle, Cali, Colombia; Hospital Universitario del Valle, Cali, Colombia
| | - P E Spiess
- Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, Estados Unidos; Department of Genitourinary Oncology and Cancer Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States; Urology and Oncology, University of South Florida, Tampa, FL, United States
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Wu H, Liu Q, Li J, Leng X, He Y, Liu Y, Zhang X, Ouyang Y, Liu Y, Liang W, Xu C. Tumor-Resident Microbiota-Based Risk Model Predicts Neoadjuvant Therapy Response of Locally Advanced Esophageal Squamous Cell Carcinoma Patients. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2309742. [PMID: 39268829 PMCID: PMC11538710 DOI: 10.1002/advs.202309742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 07/11/2024] [Indexed: 09/15/2024]
Abstract
Few predictive biomarkers exist for identifying patients who may benefit from neoadjuvant therapy (NAT). The intratumoral microbial composition is comprehensively profiled to predict the efficacy and prognosis of patients with esophageal squamous cell carcinoma (ESCC) who underwent NAT and curative esophagectomy. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis is conducted to screen for the most closely related microbiota and develop a microbiota-based risk prediction (MRP) model on the genera of TM7x, Sphingobacterium, and Prevotella. The predictive accuracy and prognostic value of the MRP model across multiple centers are validated. The MRP model demonstrates good predictive accuracy for therapeutic responses in the training, validation, and independent validation sets. The MRP model also predicts disease-free survival (p = 0.00074 in the internal validation set and p = 0.0017 in the independent validation set) and overall survival (p = 0.00023 in the internal validation set and p = 0.11 in the independent validation set) of patients. The MRP-plus model basing on MRP, tumor stage, and tumor size can also predict the patients who can benefit from NAT. In conclusion, the developed MRP and MRP-plus models may function as promising biomarkers and prognostic indicators accessible at the time of diagnosis.
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Affiliation(s)
- Hong Wu
- Department of Oncology & Cancer InstituteSichuan Academy of Medical SciencesSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan610072P. R. China
- Sichuan Cancer Hospital & InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan610041P. R. China
- Jinfeng LaboratoryChongqing400039P. R. China
- Yu‐Yue Pathology Scientific Research CenterChongqing400039P. R. China
| | - Qianshi Liu
- Department of Oncology & Cancer InstituteSichuan Academy of Medical SciencesSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan610072P. R. China
- Sichuan Cancer Hospital & InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan610041P. R. China
- Jinfeng LaboratoryChongqing400039P. R. China
- Yu‐Yue Pathology Scientific Research CenterChongqing400039P. R. China
| | - Jingpei Li
- Thoracic Surgery DepartmentThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong510230P. R. China
| | - Xuefeng Leng
- Sichuan Cancer Hospital & InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan610041P. R. China
| | - Yazhou He
- Department of OncologyWest China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan610041P. R. China
| | - Yiqiang Liu
- Department of Oncology & Cancer InstituteSichuan Academy of Medical SciencesSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan610072P. R. China
- Jinfeng LaboratoryChongqing400039P. R. China
| | - Xia Zhang
- Sichuan Cancer Hospital & InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan610041P. R. China
- Institute of Pathology and Southwest Cancer CenterMinistry of Education of ChinaSouthwest HospitalThird Military Medical University (Army Medical University) and Key Laboratory of Tumor ImmunopathologyChongqing400038P. R. China
| | - Yujie Ouyang
- Acupuncture and Massage CollegeChengdu University of Traditional Chinese MedicineChengduSichuan610072P. R. China
| | - Yang Liu
- Sichuan Cancer Hospital & InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan610041P. R. China
| | - Wenhua Liang
- Thoracic Surgery DepartmentThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong510230P. R. China
| | - Chuan Xu
- Department of Oncology & Cancer InstituteSichuan Academy of Medical SciencesSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan610072P. R. China
- Jinfeng LaboratoryChongqing400039P. R. China
- Yu‐Yue Pathology Scientific Research CenterChongqing400039P. R. China
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Jiang Y, Li Y. Nutrition Intervention and Microbiome Modulation in the Management of Breast Cancer. Nutrients 2024; 16:2644. [PMID: 39203781 PMCID: PMC11356826 DOI: 10.3390/nu16162644] [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: 07/18/2024] [Revised: 08/06/2024] [Accepted: 08/08/2024] [Indexed: 09/03/2024] Open
Abstract
Breast cancer (BC) is one of the most common cancers worldwide and a leading cause of cancer-related deaths among women. The escalating incidence of BC underscores the necessity of multi-level treatment. BC is a complex and heterogeneous disease involving many genetic, lifestyle, and environmental factors. Growing evidence suggests that nutrition intervention is an evolving effective prevention and treatment strategy for BC. In addition, the human microbiota, particularly the gut microbiota, is now widely recognized as a significant player contributing to health or disease status. It is also associated with the risk and development of BC. This review will focus on nutrition intervention in BC, including dietary patterns, bioactive compounds, and nutrients that affect BC prevention and therapeutic responses in both animal and human studies. Additionally, this paper examines the impacts of these nutrition interventions on modulating the composition and functionality of the gut microbiome, highlighting the microbiome-mediated mechanisms in BC. The combination treatment of nutrition factors and microbes is also discussed. Insights from this review paper emphasize the necessity of comprehensive BC management that focuses on the nutrition-microbiome axis.
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Affiliation(s)
| | - Yuanyuan Li
- Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA;
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Kwon SY, Thi-Thu Ngo H, Son J, Hong Y, Min JJ. Exploiting bacteria for cancer immunotherapy. Nat Rev Clin Oncol 2024; 21:569-589. [PMID: 38840029 DOI: 10.1038/s41571-024-00908-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/17/2024] [Indexed: 06/07/2024]
Abstract
Immunotherapy has revolutionized the treatment of cancer but continues to be constrained by limited response rates, acquired resistance, toxicities and high costs, which necessitates the development of new, innovative strategies. The discovery of a connection between the human microbiota and cancer dates back 4,000 years, when local infection was observed to result in tumour eradication in some individuals. However, the true oncological relevance of the intratumoural microbiota was not recognized until the turn of the twentieth century. The intratumoural microbiota can have pivotal roles in both the pathogenesis and treatment of cancer. In particular, intratumoural bacteria can either promote or inhibit cancer growth via remodelling of the tumour microenvironment. Over the past two decades, remarkable progress has been made preclinically in engineering bacteria as agents for cancer immunotherapy; some of these bacterial products have successfully reached the clinical stages of development. In this Review, we discuss the characteristics of intratumoural bacteria and their intricate interactions with the tumour microenvironment. We also describe the many strategies used to engineer bacteria for use in the treatment of cancer, summarizing contemporary data from completed and ongoing clinical trials. The work described herein highlights the potential of bacteria to transform the landscape of cancer therapy, bridging ancient wisdom with modern scientific innovation.
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Affiliation(s)
- Seong-Young Kwon
- Institute for Molecular Imaging and Theranostics, Chonnam National University Medical School, Jeonnam, Republic of Korea
- Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Jeonnam, Republic of Korea
| | - Hien Thi-Thu Ngo
- Institute for Molecular Imaging and Theranostics, Chonnam National University Medical School, Jeonnam, Republic of Korea
- Department of Biomedical Sciences, Chonnam National University Medical School, Jeonnam, Republic of Korea
- Department of Biochemistry, Hanoi Medical University, Hanoi, Vietnam
| | - Jinbae Son
- CNCure Biotech, Jeonnam, Republic of Korea
| | - Yeongjin Hong
- Institute for Molecular Imaging and Theranostics, Chonnam National University Medical School, Jeonnam, Republic of Korea
- CNCure Biotech, Jeonnam, Republic of Korea
- Department of Microbiology and Immunology, Chonnam National University Medical School, Jeonnam, Republic of Korea
- National Immunotherapy Innovation Center, Chonnam National University, Jeonnam, Republic of Korea
| | - Jung-Joon Min
- Institute for Molecular Imaging and Theranostics, Chonnam National University Medical School, Jeonnam, Republic of Korea.
- Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Jeonnam, Republic of Korea.
- Department of Biomedical Sciences, Chonnam National University Medical School, Jeonnam, Republic of Korea.
- CNCure Biotech, Jeonnam, Republic of Korea.
- Department of Microbiology and Immunology, Chonnam National University Medical School, Jeonnam, Republic of Korea.
- National Immunotherapy Innovation Center, Chonnam National University, Jeonnam, Republic of Korea.
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Tang Y, Lin TC, Yang H, Zhou Y, Sibeko L, Liu Z. High-fat diet during early life reshapes the gut microbiome and is associated with the disrupted mammary microenvironment in later life in mice. Nutr Res 2024; 127:1-12. [PMID: 38763113 DOI: 10.1016/j.nutres.2024.04.006] [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: 01/25/2024] [Revised: 04/22/2024] [Accepted: 04/27/2024] [Indexed: 05/21/2024]
Abstract
The influence of gut microbiota on gut health is well-documented, but it remains obscure for extraintestinal diseases such as breast cancer. Moreover, it is entirely unknown how gut dysbiosis during early life contributes to breast tumorigenesis later in life. In this study, we hypothesized that a high-fat diet during early life leads to alterations in the gut microbiome and is associated with disruptions in the mammary microenvironment. Female C57BL/6 mice were fed a low-fat diet (10% kcal fat) or a high-fat diet (HF, 60% kcal fat) for 8 weeks from the age of 4 to 12 weeks, which is equivalent to human childhood and adolescence. Twelve mice were sacrificed immediately after the 8-week feeding, the remainder were euthanized after switching to a normal lifecycle-supporting diet for an additional 12 weeks; the gut microbiome was then sequenced. The 8-week HF diet feeding altered the beta-diversity (Bray & Jaccard P < .01), and the difference remained significant after switching the diet (Bray & Jaccard P < .05). Immediately after HF feeding, a greater number of microbial taxa (>50) were altered, and about half of the taxa (25) remained significantly changed after switching the diet. The abundance of Alistipes, Bilophila, and Rikenellaceae stood out as significantly associated with multiple metabolic and inflammatory biomarkers in mammary tissue, including aromatase, Ccl2, and Cox2. In conclusion, an 8-week early-life HF feeding reshaped the gut microbiome, which connected with disrupted mammary microenvironments.
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Affiliation(s)
- Ying Tang
- School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA; Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA
| | - Ting-Chun Lin
- School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA
| | - Hong Yang
- Department of Oncology and Pathology, Hunan Provincial People's Hospital, Changsha, China
| | - Yanjiao Zhou
- Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA; Hunan, China
| | - Lindiwe Sibeko
- School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA
| | - Zhenhua Liu
- School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA; UMass Cancer Center, University of Massachusetts Chan Medical Chan Medical School, Worcester, MA, USA.
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Franko J, Raman S, Patel S, Petree B, Lin M, Tee MC, Le VH, Frankova D. Survival and cancer recurrence after short-course perioperative probiotics in a randomized trial. Clin Nutr ESPEN 2024; 60:59-64. [PMID: 38479940 DOI: 10.1016/j.clnesp.2024.01.003] [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: 03/05/2023] [Revised: 11/04/2023] [Accepted: 01/07/2024] [Indexed: 04/13/2024]
Abstract
BACKGROUND & AIMS The long-term impact of perioperative probiotics remains understudied while mounting evidence links microbiome and oncogenesis. Therefore, we analyzed overall survival and cancer recurrence among patients enrolled in a randomized trial of perioperative probiotics. METHODS 6-year follow-up of surgical patients participating in a randomized trial evaluating short-course perioperative oral probiotic VSL#3 (n = 57) or placebo (n = 63). RESULTS Study groups did not differ in age, preoperative hemoglobin, ASA status, and Charlson comorbidity index. There was a significant difference in preoperative serum albumin (placebo group 4.0 ± 0.1 vs. 3.7 ± 0.1 g/dL in the probiotic group, p = 0.030). Thirty-seven deaths (30.8 %) have occurred during a median follow-up of 6.2 years. Overall survival stratified on preoperative serum albumin and surgical specialty was similar between groups (p = 0.691). Age (aHR = 1.081, p = 0.001), serum albumin (aHR = 0.162, p = 0.001), and surgical specialty (aHR = 0.304, p < 0.001) were the only predictors of overall survival in the multivariate model, while the placebo/probiotic group (aHR = 0.808, p = 0.726) was not predictive. The progression rate among cancer patients was similar in the probiotic group (30.3 %, 10/33) compared to the placebo group (21.2 %, 7/33; p = 0.398). The progression-free survival was not significantly different (unstratified p = 0.270, stratified p = 0.317). CONCLUSIONS Perioperative short-course use of VSL#3 probiotics does not influence overall or progression-free survival after complex surgery for visceral malignancy.
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Affiliation(s)
- Jan Franko
- Department of Surgery, MercyOne Medical Center, Des Moines, IA, USA.
| | - Shankar Raman
- Department of Surgery, MercyOne Medical Center, Des Moines, IA, USA
| | - Shiv Patel
- Department of Surgery, MercyOne Medical Center, Des Moines, IA, USA
| | - Brandon Petree
- Department of Surgery, MercyOne Medical Center, Des Moines, IA, USA
| | - Mayin Lin
- Department of Surgery, MercyOne Medical Center, Des Moines, IA, USA
| | - May C Tee
- Department of Surgery, MercyOne Medical Center, Des Moines, IA, USA; Howard University Hospital, Washington, DC, USA
| | - Viet H Le
- Department of Surgery, MercyOne Medical Center, Des Moines, IA, USA
| | - Daniela Frankova
- Department of Internal Medicine, Des Moines University, Des Moines, IA, USA
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Zeb F, Naqeeb H, Osaili T, Faris ME, Ismail LC, Obaid RS, Naja F, Radwan H, Hasan H, Hashim M, AlBlooshi S, Alam I. Molecular crosstalk between polyphenols and gut microbiota in cancer prevention. Nutr Res 2024; 124:21-42. [PMID: 38364552 DOI: 10.1016/j.nutres.2024.01.012] [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: 09/18/2023] [Revised: 01/24/2024] [Accepted: 01/24/2024] [Indexed: 02/18/2024]
Abstract
A growing body of evidence suggests that cancer remains a significant global health challenge, necessitating the development of novel therapeutic approaches. In recent years, the molecular crosstalk between polyphenols and gut microbiota has emerged as a promising pathway for cancer prevention. Polyphenols, abundant in many plant-based foods, possess diverse bioactive properties, including antioxidant, anti-inflammatory, and anticancer activities. The gut microbiota, a complex microbial community residing in the gastrointestinal tract, plays a crucial role in a host's health and disease risks. This review highlights cancer suppressive and oncogenic mechanisms of gut microbiota, the intricate interplay between gut microbiota modulation and polyphenol biotransformation, and the potential therapeutic implications of this interplay in cancer prevention. Furthermore, this review explores the molecular mechanisms underpinning the synergistic effects of polyphenols and the gut microbiota, such as modulation of signaling pathways and immune response and epigenetic modifications in animal and human studies. The current review also summarizes the challenges and future directions in this field, including the development of personalized approaches that consider interindividual variations in gut microbiota composition and function. Understanding the molecular crosstalk could offer new perspectives for the development of personalized cancer therapies targeting the polyphenol-gut axis. Future clinical trials are needed to validate the potential role of polyphenols and gut microbiota as innovative therapeutic strategies for cancer treatment.
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Affiliation(s)
- Falak Zeb
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates.
| | - Huma Naqeeb
- Department of Clinical Nutrition, Shaukat Khanam Cancer Hospital and Research Center Peshawar, Pakistan; Department of Human Nutrition and Dietetics, Women University Mardan, Pakistan
| | - Tareq Osaili
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates; Department of Nutrition and Food Technology, Faculty of Agriculture, Jordan University of Science and Technology, Irbid, Jordan
| | - MoezAllslam Ezzat Faris
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates
| | - Leila Cheikh Ismail
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates; Department of Women's and Reproductive Health, University of Oxford, Nuffield, Oxford, United Kingdom
| | - Reyad Shakir Obaid
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates
| | - Farah Naja
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates; Nutrition and Food Sciences Department, American University of Beirut, Beirut, Lebanon
| | - Hadia Radwan
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates
| | - Hayder Hasan
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates
| | - Mona Hashim
- Research Institute for Medical and Health Sciences, University of Sharjah, United Arab Emirates; Department of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, United Arab Emirates
| | - Sharifa AlBlooshi
- College of Natural and Health Sciences, Zayed University, United Arab Emirates
| | - Iftikhar Alam
- Department of Human Nutrition and Dietetics, Bacha Khan University Charsadda, Pakistan
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12
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Sharma AD, Jarman EH, Kuppalli K, Murphy MJ, Longaker MT, Gurtner G, Fox PM. Successful topical treatment of human biofilms using multiple antibiotic elution from a collagen-rich hydrogel. Sci Rep 2024; 14:5621. [PMID: 38454046 PMCID: PMC10920629 DOI: 10.1038/s41598-024-54477-z] [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: 08/10/2023] [Accepted: 02/12/2024] [Indexed: 03/09/2024] Open
Abstract
Chronic non-healing wounds significantly strain modern healthcare systems, affecting 1-2% of the population in developed countries with costs ranging between $28.1 and $96.8 billion annually. Additionally, it has been established that chronic wounds resulting from comorbidities, such as peripheral vascular disease and diabetes mellitus, tend to be polymicrobial in nature. Treatment of polymicrobial chronic wounds with oral and IV antibiotics can result in antimicrobial resistance, leading to more difficult-to-treat wounds. Ideally, chronic ulcers would be topically treated with antibiotic combinations tailored to the microbiome of a patient's wound. We have previously shown that a topical collagen-rich hydrogel (cHG) can elute single antibiotics to inhibit bacterial growth in a manner that is nontoxic to mammalian cells. Here, we analyzed the microbiology of cultures taken from human patients diagnosed with diabetes mellitus suffering from chronic wounds present for more than 6 weeks. Additionally, we examined the safety of the elution of multiple antibiotics from collagen-rich hydrogel in mammalian cells in vivo. Finally, we aimed to create tailored combinations of antibiotics impregnated into cHG to successfully target and treat infections and eradicate biofilms cultured from human chronic diabetic wound tissue. We found that the majority of human chronic wounds in our study were polymicrobial in nature. The elution of multiple antibiotics from cHG was well-tolerated in mammalian cells, making it a potential topical treatment of the polymicrobial chronic wound. Finally, combinations of antibiotics tailored to each patient's microbiome eluted from a collagen-rich hydrogel successfully treated bacterial cultures isolated from patient samples via an in vitro assay.
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Affiliation(s)
- Ayushi D Sharma
- Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
- Division of Plastic & Reconstructive Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
- Division of Plastic & Reconstructive Surgery, Baylor Scott & White Medical Center, Temple, TX, USA
| | - Evan H Jarman
- Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
- Division of Plastic & Reconstructive Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Krutika Kuppalli
- Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Matthew J Murphy
- Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Michael T Longaker
- Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Geoffrey Gurtner
- Department of Surgery, The University of Arizona College of Medicine, Tuscon, AZ, USA
| | - Paige M Fox
- Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
- Division of Plastic & Reconstructive Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
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13
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Bibbò S, Porcari S, Del Vecchio LE, Severino A, Mullish BH, Ianiro G, Gasbarrini A, Cammarota G. Gut microbiota and immunotherapy of renal cell carcinoma. Hum Vaccin Immunother 2023; 19:2268982. [PMID: 37955340 PMCID: PMC10653624 DOI: 10.1080/21645515.2023.2268982] [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: 01/25/2023] [Accepted: 10/06/2023] [Indexed: 11/14/2023] Open
Abstract
The gut microbiome has recently been proposed as a key player in cancer development and progression. Several studies have reported that the composition of the gut microbiome plays a role in the response to immune checkpoint inhibitors (ICIs). The gut microbiome modulation has been investigated as a potential therapeutic strategy for cancer, mainly in patients undergoing therapy with ICIs. In particular, modulation through probiotics, FMT or other microbiome-related approaches have proven effective to improve the response to ICIs. In this review, we examine the role of the gut microbiome in enhancing clinical responses to ICIs in the treatment of renal cancer.
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Affiliation(s)
- Stefano Bibbò
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Serena Porcari
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Livio Enrico Del Vecchio
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Andrea Severino
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Benjamin H. Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary’s Hospital Campus, Imperial College London, London, UK
- Departments of Gastroenterology and Hepatology, St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Gianluca Ianiro
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Antonio Gasbarrini
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Giovanni Cammarota
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
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14
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Batool S, Sohail S, Ud Din F, Alamri AH, Alqahtani AS, Alshahrani MA, Alshehri MA, Choi HG. A detailed insight of the tumor targeting using nanocarrier drug delivery system. Drug Deliv 2023; 30:2183815. [PMID: 36866455 DOI: 10.1080/10717544.2023.2183815] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2023] Open
Abstract
Human struggle against the deadly disease conditions is continued since ages. The contribution of science and technology in fighting against these diseases cannot be ignored exclusively due to the invention of novel procedure and products, extending their size ranges from micro to nano. Recently nanotechnology has been gaining more consideration for its ability to diagnose and treat different cancers. Different nanoparticles have been used to evade the issues related with conservative anticancer delivery systems, including their nonspecificity, adverse effects and burst release. These nanocarriers including, solid lipid nanoparticles (SLNs), liposomes, nano lipid carriers (NLCs), nano micelles, nanocomposites, polymeric and magnetic nanocarriers, have brought revolutions in antitumor drug delivery. Nanocarriers improved the therapeutic efficacy of anticancer drugs with better accumulation at the specific site with sustained release, improved bioavailability and apoptosis of the cancer cells while bypassing the normal cells. In this review, the cancer targeting techniques and surface modification on nanoparticles are discussed briefly with possible challenges and opportunities. It can be concluded that understanding the role of nanomedicine in tumor treatment is significant, and therefore, the modern progressions in this arena is essential to be considered for a prosperous today and an affluent future of tumor patients.
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Affiliation(s)
- Sibgha Batool
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.,Nanomedicine Research Group, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Saba Sohail
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.,Nanomedicine Research Group, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Fakhar Ud Din
- Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.,Nanomedicine Research Group, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Ali H Alamri
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Ahmad S Alqahtani
- Department of Pharmacy, Mental Health Hospital, Ministry of Health, Abha, Saudi Arabia
| | - Mohammad A Alshahrani
- Department of Medical Supply in Khamis Mushet General Hospital, Ministry of Health, Khamis Mushet, Saudi Arabia
| | - Mohammed A Alshehri
- Department of Pharmacy, Abha Maternity and Children Hospital, Ministry of Health, Abha, Saudi Arabia
| | - Han Gon Choi
- College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea
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15
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He J, Li H, Jia J, Liu Y, Zhang N, Wang R, Qu W, Liu Y, Jia L. Mechanisms by which the intestinal microbiota affects gastrointestinal tumours and therapeutic effects. MOLECULAR BIOMEDICINE 2023; 4:45. [PMID: 38032415 PMCID: PMC10689341 DOI: 10.1186/s43556-023-00157-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 11/08/2023] [Indexed: 12/01/2023] Open
Abstract
The intestinal microbiota is considered to be a forgotten organ in human health and disease. It maintains intestinal homeostasis through various complex mechanisms. A significant body of research has demonstrated notable differences in the gut microbiota of patients with gastrointestinal tumours compared to healthy individuals. Furthermore, the dysregulation of gut microbiota, metabolites produced by gut bacteria, and related signal pathways can partially explain the mechanisms underlying the occurrence and development of gastrointestinal tumours. Therefore, this article summarizes the latest research progress on the gut microbiota and gastrointestinal tumours. Firstly, we provide an overview of the composition and function of the intestinal microbiota and discuss the mechanisms by which the intestinal flora directly or indirectly affects the occurrence and development of gastrointestinal tumours by regulating the immune system, producing bacterial toxins, secreting metabolites. Secondly, we present a detailed analysis of the differences of intestinal microbiota and its pathogenic mechanisms in colorectal cancer, gastric cancer, hepatocellular carcinoma, etc. Lastly, in terms of treatment strategies, we discuss the effects of the intestinal microbiota on the efficacy and toxic side effects of chemotherapy and immunotherapy and address the role of probiotics, prebiotics, FMT and antibiotic in the treatment of gastrointestinal tumours. In summary, this article provides a comprehensive review of the pathogenic mechanisms of and treatment strategies pertaining to the intestinal microbiota in patients with gastrointestinal tumours. And provide a more comprehensive and precise scientific basis for the development of microbiota-based treatments for gastrointestinal tumours and the prevention of such tumours.
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Affiliation(s)
- Jikai He
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Haijun Li
- Department of Gastrointestinal Surgery, Inner Mongolia Autonomous Region People's Hospital, Hohhot, 010017, Inner Mongolia, China
| | - Jiaqi Jia
- Graduate School of Youjiang Medical University for Nationalities, No. 98 Chengcheng Road, Youjiang District, Baise City, 533000, China
| | - Yang Liu
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Ning Zhang
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Rumeng Wang
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Wenhao Qu
- Graduate School of Youjiang Medical University for Nationalities, No. 98 Chengcheng Road, Youjiang District, Baise City, 533000, China
| | - Yanqi Liu
- Department of Gastroenterology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot City, 010050, Inner Mongolia, China.
| | - Lizhou Jia
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China.
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16
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Tortora SC, Agurto MG, Martello LA. The oral-gut-circulatory axis: from homeostasis to colon cancer. Front Cell Infect Microbiol 2023; 13:1289452. [PMID: 38029267 PMCID: PMC10663299 DOI: 10.3389/fcimb.2023.1289452] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 10/23/2023] [Indexed: 12/01/2023] Open
Abstract
The human microbiota is widely recognized as providing crucial health benefits to its host, specifically by modulating immune homeostasis. Microbial imbalance, known as dysbiosis, is linked to several conditions in the body. The oral cavity and gut host the two largest microbial communities playing a major role in microbial-associated diseases. While the oral-gut axis has been previously explored, our review uniquely highlights the significance of incorporating the circulatory system into this axis. The interaction between immune cells, inflammatory factors, circulating bacteria, and microbial metabolites influences the homeostasis of both the oral and gut microbiota in a bidirectional manner. In this comprehensive review, we aim to describe the bacterial components of the oral-gut-circulatory axis in both health and disease, with a specific focus on colon cancer.
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Affiliation(s)
- Sofia C. Tortora
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY, United States
| | - Maria Gonzalez Agurto
- Departamento de Rehabilitación Craneofacial Integral, Universidad de Los Andes, Santiago, Chile
| | - Laura A. Martello
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY, United States
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17
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Sun J, Chen F, Wu G. Potential effects of gut microbiota on host cancers: focus on immunity, DNA damage, cellular pathways, and anticancer therapy. THE ISME JOURNAL 2023; 17:1535-1551. [PMID: 37553473 PMCID: PMC10504269 DOI: 10.1038/s41396-023-01483-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 07/14/2023] [Accepted: 07/20/2023] [Indexed: 08/10/2023]
Abstract
The symbiotic bacteria that live in the human gut and the metabolites they produce have long influenced local and systemic physiological and pathological processes of the host. The gut microbiota are increasingly being recognized for its impact on a range of human diseases, including cancer, it may play a key role in the occurrence, progression, treatment, and prognosis of many types of cancer. Understanding the functional role of the gut microbiota in cancer is crucial for the development of the era of personalized medicine. Here, we review recent advances in research and summarize the important associations and clear experimental evidence for the role of the gut microbiota in a variety of human cancers, focus on the application and possible challenges associated with the gut microbiota in antitumor therapy. In conclusion, our research demonstrated the multifaceted mechanisms of gut microbiota affecting human cancer and provides directions and ideas for future clinical research.
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Affiliation(s)
- Jiaao Sun
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China
| | - Feng Chen
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
| | - Guangzhen Wu
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
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18
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Fernández-Murga ML, Gil-Ortiz F, Serrano-García L, Llombart-Cussac A. A New Paradigm in the Relationship between Gut Microbiota and Breast Cancer: β-glucuronidase Enzyme Identified as Potential Therapeutic Target. Pathogens 2023; 12:1086. [PMID: 37764894 PMCID: PMC10535898 DOI: 10.3390/pathogens12091086] [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: 07/12/2023] [Revised: 08/22/2023] [Accepted: 08/23/2023] [Indexed: 09/29/2023] Open
Abstract
Breast cancer (BC) is the most frequently occurring malignancy and the second cancer-specific cause of mortality in women in developed countries. Over 70% of the total number of BCs are hormone receptor-positive (HR+), and elevated levels of circulating estrogen (E) in the blood have been shown to be a major risk factor for the development of HR+ BC. This is attributable to estrogen's contribution to increased cancer cell proliferation, stimulation of angiogenesis and metastasis, and resistance to therapy. The E metabolism-gut microbiome axis is functional, with subjacent individual variations in the levels of E. It is conceivable that the estrobolome (bacterial genes whose products metabolize E) may contribute to the risk of malignant neoplasms of hormonal origin, including BC, and may serve as a potential biomarker and target. It has been suggested that β-glucuronidase (GUS) enzymes of the intestinal microbiome participate in the strobolome. In addition, it has been proposed that bacterial GUS enzymes from the gastrointestinal tract participate in hormone BC. In this review, we discuss the latest knowledge about the role of the GUS enzyme in the pathogenesis of BC, focusing on (i) the microbiome and E metabolism; (ii) diet, estrobolome, and BC development; (iii) other activities of the bacterial GUS; and (iv) the new molecular targets for BC therapeutic application.
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Affiliation(s)
- M. Leonor Fernández-Murga
- Clinical and Molecular Oncology Laboratory, Hospital Arnau de Vilanova-Liria, FISABIO, 46015 Valencia, Spain; (L.S.-G.); (A.L.-C.)
| | | | - Lucía Serrano-García
- Clinical and Molecular Oncology Laboratory, Hospital Arnau de Vilanova-Liria, FISABIO, 46015 Valencia, Spain; (L.S.-G.); (A.L.-C.)
| | - Antonio Llombart-Cussac
- Clinical and Molecular Oncology Laboratory, Hospital Arnau de Vilanova-Liria, FISABIO, 46015 Valencia, Spain; (L.S.-G.); (A.L.-C.)
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19
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Kaluanga Bwanga P, Tremblay-Lemoine PL, Timmermans M, Ravet S, Munaut C, Nisolle M, Henry L. The Endometrial Microbiota: Challenges and Prospects. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1540. [PMID: 37763663 PMCID: PMC10534531 DOI: 10.3390/medicina59091540] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/14/2023] [Accepted: 08/22/2023] [Indexed: 09/29/2023]
Abstract
Contrary to popular belief, we have known for many years that the endometrium is not a sterile environment and is considered to be a low-biomass milieu compared to the vagina. Numerous trials and studies have attempted to establish a valid sampling method and assess its physiological composition, but no consensus has been reached. Many factors, such as ethnicity, age and inflammation, can influence the microbiome. Moreover, it possesses a higher alpha-diversity and, therefore, contains more diverse bacteria than the vagina. For instance, Lactobacillus has been shown to be a predominant genus in the vaginal microbiome of healthy women. Consequently, even if a majority of scientists postulate that a predominance of Lactobacillus inside the uterus improves reproductive outcomes, vaginal contamination by these bacteria during sampling cannot be ruled out. Certain pathologies, such as chronic endometritis, have been identified as inflammation perpetrators that hinder the embryo implantation process. This pro-inflammatory climate created by dysbiosis of the endometrial microbiota could induce secondary inflammatory mediators via Toll-like receptors, creating an environment conducive to the development of endometriosis and even promoting carcinogenesis. However, studies to this day have focused on small populations. In addition, there is no clearly defined healthy uterine composition yet. At most, only a few taxa have been identified as pathogenic. As sampling and analysis methods become increasingly precise, we can expect the endometrial microbiota to be incorporated into future diagnostic tools and treatments for women's health.
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Affiliation(s)
| | - Pierre-Luc Tremblay-Lemoine
- Department of Obstetrics and Gynecology, CHU of Liege-Citadelle Site, University of Liège, 4000 Liège, Belgium
| | - Marie Timmermans
- Department of Obstetrics and Gynecology, CHU of Liege-Citadelle Site, University of Liège, 4000 Liège, Belgium
| | - Stéphanie Ravet
- Center for Reproductive Medicine, University of Liège-Citadelle Site, 4000 Liege, Belgium
| | - Carine Munaut
- Laboratory of Tumor and Development Biology, Giga-Cancer, University of Liège, 4000 Liège, Belgium
| | - Michelle Nisolle
- Department of Obstetrics and Gynecology, CHU of Liege-Citadelle Site, University of Liège, 4000 Liège, Belgium
| | - Laurie Henry
- Department of Obstetrics and Gynecology, CHU of Liege-Citadelle Site, University of Liège, 4000 Liège, Belgium
- Center for Reproductive Medicine, University of Liège-Citadelle Site, 4000 Liege, Belgium
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20
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Fonti N, Parisi F, Mancianti F, Freer G, Poli A. Cancerogenic parasites in veterinary medicine: a narrative literature review. Infect Agent Cancer 2023; 18:45. [PMID: 37496079 PMCID: PMC10373346 DOI: 10.1186/s13027-023-00522-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 07/17/2023] [Indexed: 07/28/2023] Open
Abstract
Parasite infection is one of the many environmental factors that can significantly contribute to carcinogenesis and is already known to be associated with a variety of malignancies in both human and veterinary medicine. However, the actual number of cancerogenic parasites and their relationship to tumor development is far from being fully understood, especially in veterinary medicine. Thus, the aim of this review is to investigate parasite-related cancers in domestic and wild animals and their burden in veterinary oncology. Spontaneous neoplasia with ascertained or putative parasite etiology in domestic and wild animals will be reviewed, and the multifarious mechanisms of protozoan and metazoan cancer induction will be discussed.
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Affiliation(s)
- Niccolò Fonti
- Dipartimento di Scienze veterinarie, Università di Pisa, Viale delle Piagge, 2, 56124, Pisa, Italy.
| | - Francesca Parisi
- Dipartimento di Scienze veterinarie, Università di Pisa, Viale delle Piagge, 2, 56124, Pisa, Italy
| | - Francesca Mancianti
- Dipartimento di Scienze veterinarie, Università di Pisa, Viale delle Piagge, 2, 56124, Pisa, Italy
| | - Giulia Freer
- Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa, Via Savi, 10, 56126, Pisa, Italy
| | - Alessandro Poli
- Dipartimento di Scienze veterinarie, Università di Pisa, Viale delle Piagge, 2, 56124, Pisa, Italy
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21
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Elie C, Perret M, Hage H, Sentausa E, Hesketh A, Louis K, Fritah-Lafont A, Leissner P, Vachon C, Rostaing H, Reynier F, Gervasi G, Saliou A. Comparison of DNA extraction methods for 16S rRNA gene sequencing in the analysis of the human gut microbiome. Sci Rep 2023; 13:10279. [PMID: 37355726 PMCID: PMC10290636 DOI: 10.1038/s41598-023-33959-6] [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: 10/21/2022] [Accepted: 04/21/2023] [Indexed: 06/26/2023] Open
Abstract
The gut microbiome is widely analyzed using high-throughput sequencing, such as 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing (SMS). DNA extraction is known to have a large impact on the metagenomic analyses. The aim of this study was to compare DNA extraction protocols for 16S sequencing. In that context, four commonly used DNA extraction methods were compared for the analysis of the gut microbiota. Commercial versions were evaluated against modified protocols using a stool preprocessing device (SPD, bioMérieux) upstream DNA extraction. Stool samples from nine healthy volunteers and nine patients with a Clostridium difficile infection were extracted with all protocols and 16S sequenced. Protocols were ranked using wet- and dry-lab criteria, including quality controls of the extracted genomic DNA, alpha-diversity, accuracy using a mock community of known composition and repeatability across technical replicates. SPD improved overall efficiency of three of the four tested protocols compared with their commercial version, in terms of DNA extraction yield, sample alpha-diversity, and recovery of Gram-positive bacteria. The best overall performance was obtained for the S-DQ protocol, SPD combined with the DNeasy PowerLyser PowerSoil protocol from QIAGEN. Based on this evaluation, we strongly believe that the use of such stool preprocessing device improves both the standardization and the quality of the DNA extraction in the human gut microbiome studies.
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Affiliation(s)
- Céline Elie
- BIOASTER, Microbiology Research Institute, 40 avenue Tony Garnier, 69007, Lyon, France
| | - Magali Perret
- BIOASTER, Microbiology Research Institute, 40 avenue Tony Garnier, 69007, Lyon, France
| | - Hayat Hage
- BIOASTER, Microbiology Research Institute, 40 avenue Tony Garnier, 69007, Lyon, France
| | - Erwin Sentausa
- BIOASTER, Microbiology Research Institute, 40 avenue Tony Garnier, 69007, Lyon, France
| | - Amy Hesketh
- BIOASTER, Microbiology Research Institute, 40 avenue Tony Garnier, 69007, Lyon, France
| | - Karen Louis
- BIOASTER, Microbiology Research Institute, 40 avenue Tony Garnier, 69007, Lyon, France
| | - Asmaà Fritah-Lafont
- BIOASTER, Microbiology Research Institute, 40 avenue Tony Garnier, 69007, Lyon, France
| | - Philippe Leissner
- BIOASTER, Microbiology Research Institute, 40 avenue Tony Garnier, 69007, Lyon, France
| | - Carole Vachon
- bioMérieux, 5 Rue des Berges, 38000, Grenoble, France
| | | | - Frédéric Reynier
- BIOASTER, Microbiology Research Institute, 40 avenue Tony Garnier, 69007, Lyon, France
| | - Gaspard Gervasi
- bioMérieux, 376 Chemin de l'Orme, 69280, Marcy-l'Étoile, France
| | - Adrien Saliou
- BIOASTER, Microbiology Research Institute, 40 avenue Tony Garnier, 69007, Lyon, France.
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22
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Zha C, Peng Z, Huang K, Tang K, Wang Q, Zhu L, Che B, Li W, Xu S, Huang T, Yu Y, Zhang W. Potential role of gut microbiota in prostate cancer: immunity, metabolites, pathways of action? Front Oncol 2023; 13:1196217. [PMID: 37265797 PMCID: PMC10231684 DOI: 10.3389/fonc.2023.1196217] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 05/04/2023] [Indexed: 06/03/2023] Open
Abstract
The gut microbiota helps to reveal the relationship between diseases, but the role of gut microbiota in prostate cancer (PCa) is still unclear. Recent studies have found that the composition and abundance of specific gut microbiota are significantly different between PCa and non-PCa, and the gut microbiota may have common and unique characteristics between different diseases. Intestinal microorganisms are affected by various factors and interact with the host in a variety of ways. In the complex interaction model, the regulation of intestinal microbial metabolites and the host immune system is particularly important, and they play a key role in maintaining the ecological balance of intestinal microorganisms and metabolites. However, specific changes in the composition of intestinal microflora may promote intestinal mucosal immune imbalance, leading to the formation of tumors. Therefore, this review analyzes the immune regulation of intestinal flora and the production of metabolites, as well as their effects and mechanisms on tumors, and briefly summarizes that specific intestinal flora can play an indirect role in PCa through their metabolites, genes, immunity, and pharmacology, and directly participate in the occurrence, development, and treatment of tumors through bacterial and toxin translocation. We also discussed markers of high risk PCa for intestinal microbiota screening and the possibility of probiotic ingestion and fecal microbiota transplantation, in order to provide better treatment options for clinic patients. Finally, after summarizing a number of studies, we found that changes in immunity, metabolites.
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Affiliation(s)
- Cheng Zha
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Zheng Peng
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Kunyuan Huang
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Kaifa Tang
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- Department of Urology & Andrology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Qiang Wang
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Lihua Zhu
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Bangwei Che
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Wei Li
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Shenghan Xu
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Tao Huang
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Ying Yu
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Wenjun Zhang
- Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
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Chai Y, Huang Z, Shen X, Lin T, Zhang Y, Feng X, Mao Q, Liang Y. Microbiota Regulates Pancreatic Cancer Carcinogenesis through Altered Immune Response. Microorganisms 2023; 11:1240. [PMID: 37317214 PMCID: PMC10221276 DOI: 10.3390/microorganisms11051240] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 05/02/2023] [Accepted: 05/04/2023] [Indexed: 06/16/2023] Open
Abstract
The microbiota is present in many parts of the human body and plays essential roles. The most typical case is the occurrence and development of cancer. Pancreatic cancer (PC), one of the most aggressive and lethal types of cancer, has recently attracted the attention of researchers. Recent research has revealed that the microbiota regulates PC carcinogenesis via an altered immune response. Specifically, the microbiota, in several sites, including the oral cavity, gastrointestinal tract, and pancreatic tissue, along with the numerous small molecules and metabolites it produces, influences cancer progression and treatment by activating oncogenic signaling, enhancing oncogenic metabolic pathways, altering cancer cell proliferation, and triggering chronic inflammation that suppresses tumor immunity. Diagnostics and treatments based on or in combination with the microbiota offer novel insights to improve efficiency compared with existing therapies.
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Affiliation(s)
- Yihan Chai
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Zhengze Huang
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Xuqiu Shen
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Tianyu Lin
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Yiyin Zhang
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Xu Feng
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
| | - Qijiang Mao
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
- Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Hangzhou 310016, China
- Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou 310028, China
| | - Yuelong Liang
- Department of General Surgery, Zhejiang University School of Medicine, Sir Run Run Shaw Hospital, Hangzhou 310016, China
- Zhejiang Province Medical Research Center of Minimally Invasive Diagnosis and Treatment of Abdominal Diseases, Hangzhou 310028, China
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Nicolò S, Antonelli A, Tanturli M, Baccani I, Bonaiuto C, Castronovo G, Rossolini GM, Mattiuz G, Torcia MG. Bacterial Species from Vaginal Microbiota Differently Affect the Production of the E6 and E7 Oncoproteins and of p53 and p-Rb Oncosuppressors in HPV16-Infected Cells. Int J Mol Sci 2023; 24:ijms24087173. [PMID: 37108333 PMCID: PMC10138431 DOI: 10.3390/ijms24087173] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/07/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
Vaginal dysbiosis is characterized by a decrease in the relative abundance of Lactobacillus species in favor of other species. This condition facilitates infections by sexually transmitted pathogens including high risk (HR)-human papilloma viruses (HPVs) involved in the development of cervical cancer. Some vaginal dysbiosis bacteria contribute to the neoplastic progression by inducing chronic inflammation and directly activating molecular pathways involved in carcinogenesis. In this study, SiHa cells, an HPV-16-transformed epithelial cell line, were exposed to different representative vaginal microbial communities. The expression of the HPV oncogenes E6 and E7 and the production of relative oncoproteins was evaluated. The results showed that Lactobacillus crispatus and Lactobacillus gasseri modulated the basal expression of the E6 and E7 genes of SiHa cells and the production of the E6 and E7 oncoproteins. Vaginal dysbiosis bacteria had contrasting effects on E6/E7 gene expression and protein production. The expression of the E6 and E7 genes and the production of the relative oncoproteins was increased by strains of Gardnerella vaginalis and, to a lesser extent, by Megasphaera micronuciformis. In contrast, Prevotella bivia decreased the expression of oncogenes and the production of the E7 protein. A decreased amount of p53 and pRb was found in the cultures of SiHa cells with M. micronuciformis, and accordingly, in the same cultures, a higher percentage of cells progressed to the S-phase of the cell cycle compared to the untreated or Lactobacillus-stimulated cultures. These data confirm that L. crispatus represents the most protective component of the vaginal microbiota against neoplastic progression of HR-HPV infected cells, while M. micronuciformis and, to a lesser extent, G. vaginalis may directly interfere in the oncogenic process, inducing or maintaining the production of viral oncoproteins.
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Affiliation(s)
- Sabrina Nicolò
- Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy
| | - Alberto Antonelli
- Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy
- Clinical Microbiology and Virology Unit, Careggi University Hospital, 50139 Florence, Italy
| | - Michele Tanturli
- Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy
| | - Ilaria Baccani
- Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy
- Clinical Microbiology and Virology Unit, Careggi University Hospital, 50139 Florence, Italy
| | - Chiara Bonaiuto
- Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy
- Clinical Microbiology and Virology Unit, Careggi University Hospital, 50139 Florence, Italy
| | - Giuseppe Castronovo
- Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy
| | - Gian Maria Rossolini
- Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy
- Clinical Microbiology and Virology Unit, Careggi University Hospital, 50139 Florence, Italy
| | - G Mattiuz
- Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy
| | - M G Torcia
- Department of Clinical and Experimental Medicine, University of Florence, 50134 Florence, Italy
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Wang D, Ji DC, Yu CY, Wu DN, Qi L. Research progress on the mitochondrial mechanism of age-related non-alcoholic fatty liver. World J Gastroenterol 2023; 29:1982-1993. [PMID: 37155524 PMCID: PMC10122792 DOI: 10.3748/wjg.v29.i13.1982] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/20/2023] [Accepted: 03/13/2023] [Indexed: 04/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Reduced activity and slower metabolism in the elderly affect the balance of lipid metabolism in the liver leading to the accumulation of lipids. This affects the mitochondrial respiratory chain and the efficiency of β-oxidation and induces the overproduction of reactive oxygen species. In addition, the dynamic balance of the mitochondria is disrupted during the ageing process, which inhibits its phagocytic function and further aggravates liver injury, leading to a higher incidence of NAFLD in the elderly population. The present study reviewed the manifestations, role and mechanism of mitochondrial dysfunction in the progression of NAFLD in the elderly. Based on the understanding of mitochondrial dysfunction and abnormal lipid metabolism, this study discusses the treatment strategies and the potential therapeutic targets for NAFLD, including lipid accumulation, antioxidation, mitophagy and liver-protecting drugs. The purpose is to provide new ideas for the development of innovative drugs for the prevention and treatment of NAFLD.
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Affiliation(s)
- Dan Wang
- College of Basic Medicine, Beihua University, Jilin 132013, Jilin Province, China
| | - Duo-Chun Ji
- College of Basic Medicine, Beihua University, Jilin 132013, Jilin Province, China
| | - Chun-Yan Yu
- College of Basic Medicine, Beihua University, Jilin 132013, Jilin Province, China
| | - Dan-Ni Wu
- College of Basic Medicine, Beihua University, Jilin 132013, Jilin Province, China
| | - Ling Qi
- Central Laboratory, Qingyuan People's Hospital, Qingyuan 511518, Guangdong Province, China
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26
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Viswanathan S, Parida S, Lingipilli BT, Krishnan R, Podipireddy DR, Muniraj N. Role of Gut Microbiota in Breast Cancer and Drug Resistance. Pathogens 2023; 12:pathogens12030468. [PMID: 36986390 PMCID: PMC10058520 DOI: 10.3390/pathogens12030468] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 03/08/2023] [Accepted: 03/13/2023] [Indexed: 03/19/2023] Open
Abstract
Breast cancer is the most common malignancy in women worldwide. The cause of cancer is multifactorial. An early diagnosis and the appropriate treatment of cancer can improve the chances of survival. Recent studies have shown that breast cancer is influenced by the microbiota. Different microbial signatures have been identified in the breast microbiota, which have different patterns depending on the stage and biological subgroups. The human digestive system contains approximately 100 trillion bacteria. The gut microbiota is an emerging field of research that is associated with specific biological processes in many diseases, including cardiovascular disease, obesity, diabetes, brain disease, rheumatoid arthritis, and cancer. In this review article, we discuss the impact of the microbiota on breast cancer, with a primary focus on the gut microbiota’s regulation of the breast cancer microenvironment. Ultimately, updates on how immunotherapy can affect the breast cancer-based microbiome and further clinical trials on the breast and microbiome axis may be an important piece of the puzzle in better predicting breast cancer risk and prognosis.
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Affiliation(s)
| | - Sheetal Parida
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Bhuvana Teja Lingipilli
- Gandhi Institute of Technology and Management (GITAM), Deemed University, Visakhapatnam 530045, Andhra Pradesh, India
| | - Ramalingam Krishnan
- Department of Biochemistry, Narayana Medical College, Nellore 524003, Andhra Pradesh, India
| | - Devendra Rao Podipireddy
- Rangaraya Medical College, Dr. YSR University of Health Sciences, Kakinada 533001, Andhra Pradesh, India
| | - Nethaji Muniraj
- Center for Cancer and Immunology Research, Children’s National Hospital, 111, Michigan Ave NW, Washington, DC 20010, USA
- Correspondence: ; Tel.: +1-202-476-2466
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The Role of Silver Nanoparticles in the Diagnosis and Treatment of Cancer: Are There Any Perspectives for the Future? Life (Basel) 2023; 13:life13020466. [PMID: 36836823 PMCID: PMC9965924 DOI: 10.3390/life13020466] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 02/02/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023] Open
Abstract
Cancer is a fatal disease with a complex pathophysiology. Lack of specificity and cytotoxicity, as well as the multidrug resistance of traditional cancer chemotherapy, are the most common limitations that often cause treatment failure. Thus, in recent years, significant efforts have concentrated on the development of a modernistic field called nano-oncology, which provides the possibility of using nanoparticles (NPs) with the aim to detect, target, and treat cancer diseases. In comparison with conventional anticancer strategies, NPs provide a targeted approach, preventing undesirable side effects. What is more, nanoparticle-based drug delivery systems have shown good pharmacokinetics and precise targeting, as well as reduced multidrug resistance. It has been documented that, in cancer cells, NPs promote reactive oxygen species (ROS) production, induce cell cycle arrest and apoptosis, activate ER (endoplasmic reticulum) stress, modulate various signaling pathways, etc. Furthermore, their ability to inhibit tumor growth in vivo has also been documented. In this paper, we have reviewed the role of silver NPs (AgNPs) in cancer nanomedicine, discussing numerous mechanisms by which they render anticancer properties under both in vitro and in vivo conditions, as well as their potential in the diagnosis of cancer.
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28
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Xu Y, Zhao J, Ma Y, Liu J, Cui Y, Yuan Y, Xiang C, Ma D, Liu H. The microbiome types of colorectal tissue are potentially associated with the prognosis of patients with colorectal cancer. Front Microbiol 2023; 14:1100873. [PMID: 37025624 PMCID: PMC10072283 DOI: 10.3389/fmicb.2023.1100873] [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] [Received: 11/17/2022] [Accepted: 02/28/2023] [Indexed: 04/08/2023] Open
Abstract
As the second leading cause of cancer worldwide, colorectal cancer (CRC) is associated with a poor prognosis. Although recent studies have explored prognostic markers in patients with CRC, whether tissue microbes carry prognostic information remains unknown. Here, by assessing the colorectal tissue microbes of 533 CRC patients, we found that Proteobacteria (43.5%), Firmicutes (25.3%), and Actinobacteria (23.0%) dominated the colorectal tissue microbiota, which was different from the gut microbiota. Moreover, two clear clusters were obtained by clustering based on the tissue microbes across all samples. By comparison, the relative abundances of Proteobacteria and Bacteroidetes in cluster 1 were significantly higher than those in cluster 2; while compared with cluster 1, Firmicutes and Actinobacteria were more abundant in cluster 2. In addition, the Firmicutes/Bacteroidetes ratios in cluster 1 were significantly lower than those in cluster 2. Further, compared with cluster 2, patients in cluster 1 had relatively poor survival (Log-rank test, p = 0.0067). By correlating tissue microbes with patient survival, we found that the relative abundance of dominant phyla, including Proteobacteria, Firmicutes, and Bacteroidetes, was significantly associated with survival in CRC patients. Besides, the co-occurrence network of tissue microbes at the phylum level of cluster 2 was more complicated than that of cluster 1. Lastly, we detected some pathogenic bacteria enriched in cluster 1 that promote the development of CRC, thus leading to poor survival. In contrast, cluster 2 showed significant increases in the abundance of some probiotics and genera that resist cancer development. Altogether, this study provides the first evidence that the tissue microbiome of CRC patients carries prognostic information and can help design approaches for clinically evaluating the survival of CRC patients.
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Affiliation(s)
- Yixin Xu
- Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Jing Zhao
- Department of Pathology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yu Ma
- Department of Pathology, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Jia Liu
- Department of Pathology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yingying Cui
- Department of Pathology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yuqing Yuan
- Department of Pathology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Chenxi Xiang
- Department of Pathology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Dongshen Ma
- Department of Pathology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- *Correspondence: Hui Liu, ; Dongshen Ma,
| | - Hui Liu
- Department of Pathology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Pathology, Xuzhou Medical University, Xuzhou, Jiangsu, China
- *Correspondence: Hui Liu, ; Dongshen Ma,
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29
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Quantitative Metabolomics to Explore the Role of Plasma Polyamines in Colorectal Cancer. Int J Mol Sci 2022; 24:ijms24010101. [PMID: 36613539 PMCID: PMC9820724 DOI: 10.3390/ijms24010101] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/14/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is one of the major public health and socio-economic problems, which management demands the development of non-invasive screening tests. Assessment of circulating polyamines could be a valuable tool, although analytical problems still preclude its clinical practice. We exploited ultra-high-resolution liquid chromatography and mass spectrometry, as a highly sensitive and innovative method, to profile eleven polyamines, including spermine and spermidine with their acetylated forms. These data together with an evaluation of the inflammatory indexes might represent suitable biomarkers for the identification of CRC patients. The statistical models revealed good discrimination in distinguishing CRC patients from healthy subjects. The plasma assessment of ornithine and acetylspermine, as well as lymphocyte/platelet ratio, revealed helpful information on the progression of CRC. The combined profiles of circulating polyamines and inflammatory indexes, together with the application of an innovative technology, could represent a valuable tool for discriminating patients from different clinical groups.
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30
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Gut Microbiota and Therapy in Metastatic Melanoma: Focus on MAPK Pathway Inhibition. Int J Mol Sci 2022; 23:ijms231911990. [PMID: 36233289 PMCID: PMC9569448 DOI: 10.3390/ijms231911990] [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: 09/13/2022] [Revised: 10/04/2022] [Accepted: 10/05/2022] [Indexed: 11/06/2022] Open
Abstract
Gut microbiome (GM) and its either pro-tumorigenic or anti-tumorigenic role is intriguing and constitutes an evolving landscape in translational oncology. It has been suggested that these microorganisms may be involved in carcinogenesis, cancer treatment response and resistance, as well as predisposition to adverse effects. In melanoma patients, one of the most immunogenic cancers, immune checkpoint inhibitors (ICI) and MAPK-targeted therapy—BRAF/MEK inhibitors—have revolutionized prognosis, and the study of the microbiome as a modulating factor is thus appealing. Although BRAF/MEK inhibitors constitute one of the main backbones of treatment in melanoma, little is known about their impact on GM and how this might correlate with immune re-induction. On the contrary, ICI and their relationship to GM has become an interesting field of research due to the already-known impact of immunotherapy in modulating the immune system. Immune reprogramming in the tumor microenvironment has been established as one of the main targets of microbiome, since it can induce immunosuppressive phenotypes, promote inflammatory responses or conduct anti-tumor responses. As a result, ongoing clinical trials are evaluating the role of fecal microbiota transplant (FMT), as well as the impact of using dietary supplements, antibiotics and probiotics in the prediction of response to therapy. In this review, we provide an overview of GM’s link to cancer, its relationship with the immune system and how this may impact response to treatments in melanoma patients. We also discuss insights about novel therapeutic approaches including FMT, changes in diet and use of probiotics, prebiotics and symbiotics. Finally, we hypothesize on the possible pathways through which GM may impact anti-tumor efficacy in melanoma patients treated with targeted therapy, an appealing subject of which little is known.
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31
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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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32
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Anik MI, Mahmud N, Masud AA, Khan MI, Islam MN, Uddin S, Hossain MK. Role of Reactive Oxygen Species in Aging and Age-Related Diseases: A Review. ACS APPLIED BIO MATERIALS 2022; 5:4028-4054. [PMID: 36043942 DOI: 10.1021/acsabm.2c00411] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Research on the role of reactive oxygen species (ROS) in the aging process has advanced significantly over the last two decades. In light of recent findings, ROS takes part in the aging process of cells along with contributing to various physiological signaling pathways. Antioxidants being cells' natural defense mechanism against ROS-mediated alteration, play an imperative role to maintain intracellular ROS homeostasis. Although the complete understanding of the ROS regulated aging process is yet to be fully comprehended, current insights into various sources of cellular ROS and their correlation with the aging process and age-related diseases are portrayed in this review. In addition, results on the effect of antioxidants on ROS homeostasis and the aging process as well as their advances in clinical trials are also discussed in detail. The future perspective in ROS-antioxidant dynamics on antiaging research is also marshaled to provide future directions for ROS-mediated antiaging research fields.
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Affiliation(s)
- Muzahidul I Anik
- Department of Chemical Engineering, University of Rhode Island, Kingston, Rhode Island 02881, United States
| | - Niaz Mahmud
- Department of Biomedical Engineering, Military Institute of Science and Technology, Dhaka 1216, Bangladesh
| | - Abdullah Al Masud
- Department of Chemical Engineering, Bangladesh University of Engineering and Technology, Dhaka 1000, Bangladesh
| | - Md Ishak Khan
- Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Md Nurul Islam
- Department of Bioregulatory Sciences, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
| | - Shihab Uddin
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
- Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, Fukuoka 819-0395, Japan
| | - M Khalid Hossain
- Institute of Electronics, Atomic Energy Research Establishment, Bangladesh Atomic Energy Commission, Dhaka 1349, Bangladesh
- Interdisciplinary Graduate School of Engineering Science, Kyushu University, Fukuoka 816-8580, Japan
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Live Biotherapeutic Lactococcus lactis GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System. Cancers (Basel) 2022; 14:cancers14174083. [PMID: 36077619 PMCID: PMC9455052 DOI: 10.3390/cancers14174083] [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: 07/07/2022] [Revised: 08/16/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Recent studies, which have revealed the strong relationship between gut microbiota and tumor progression, have driven the clinical application of microbiome-based treatments to increase the efficacy of anticancer therapies. In particular, the genome-editing Lactococcus lactis, which activates the host immune system by expressing immune-boosting cytokines or metabolites, is a candidate for microbiome treatment. While Lactococcus lactis has so far been studied in terms of its recombinant forms, we investigated the anticancer effects of the strain-specific Lactococcus lactis GEN3013 itself. In vitro cytotoxicity tests showed that L. lactis GEN3013 inhibited the cell growth of various human and murine cancer cell lines. Consistent with the in vitro results, L. lactis GEN3013 showed antitumor effects and enhanced the therapeutic efficacy of both chemotherapy and immunotherapy in syngeneic mice. In addition, the host immune system was activated both locally and systemically by the combinatorial treatment of L. lactis GEN3013 with chemotherapy and immunotherapy. For these reasons, we suggest that L. lactis GEN3013 could be utilized as a novel biotherapeutic agent for cancer treatment. Abstract The gut microbiota is responsible for differential anticancer drug efficacies by modulating the host immune system and the tumor microenvironment. Interestingly, this differential effect is highly strain-specific. For example, certain strains can directly suppress tumor growth and enhance antitumor immunity; however, others do not have such an effect or even promote tumor growth. Identifying effective strains that possess antitumor effects is key for developing live biotherapeutic anticancer products. Here, we found that Lactococcus lactis GEN3013 inhibits tumor growth by regulating tumor angiogenesis and directly inducing cancer cell death. Moreover, L. lactis GEN3013 enhanced the therapeutic effects of oxaliplatin and the PD-1 blockade. Comprehensive immune profiling showed that L. lactis GEN3013 augmented cytotoxic immune cell populations, such as CD4+ T cells, CD8+ effector T cells, and NK cells in the tumor microenvironment. Our results indicate that L. lactis GEN3013 is a promising candidate for potentiating cancer treatment in combination with current standard therapy.
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Giron LB, Peluso MJ, Ding J, Kenny G, Zilberstein NF, Koshy J, Hong KY, Rasmussen H, Miller GE, Bishehsari F, Balk RA, Moy JN, Hoh R, Lu S, Goldman AR, Tang HY, Yee BC, Chenna A, Winslow JW, Petropoulos CJ, Kelly JD, Wasse H, Martin JN, Liu Q, Keshavarzian A, Landay A, Deeks SG, Henrich TJ, Abdel-Mohsen M. Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling. JCI Insight 2022; 7:e160989. [PMID: 35727635 PMCID: PMC9462470 DOI: 10.1172/jci.insight.160989] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 06/17/2022] [Indexed: 11/24/2022] Open
Abstract
Long COVID, a type of post-acute sequelae of SARS-CoV-2 (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the mechanisms that drive this inflammation remain unknown. Inflammation during acute coronavirus disease 2019 could be exacerbated by microbial translocation (from the gut and/or lung) to blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We did not observe a significant elevation in plasma markers of bacterial translocation during PASC. However, we observed higher levels of fungal translocation - measured as β-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared with those without PASC or SARS-CoV-2-negative controls. The higher β-glucan correlated with higher inflammation and elevated levels of host metabolites involved in activating N-methyl-d-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neurotoxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via Dectin-1) and activating Syk/NF-κB signaling. Using a Dectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared with plasma from negative controls. This higher NF-κB signaling was abrogated by piceatannol (Syk inhibitor). These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.
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Affiliation(s)
| | | | - Jianyi Ding
- The Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Grace Kenny
- Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland
| | | | - Jane Koshy
- The Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Kai Ying Hong
- The Wistar Institute, Philadelphia, Pennsylvania, USA
| | | | | | - Faraz Bishehsari
- Department of Internal Medicine, Rush University, Chicago, Illinois, USA
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University, Chicago, Illinois, USA
| | - Robert A. Balk
- Department of Internal Medicine, Rush University, Chicago, Illinois, USA
| | - James N. Moy
- Department of Internal Medicine, Rush University, Chicago, Illinois, USA
| | | | - Scott Lu
- UCSF, San Francisco, California, USA
| | | | - Hsin-Yao Tang
- The Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Brandon C. Yee
- Monogram Biosciences, Inc., Labcorp, South San Francisco, California, USA
| | - Ahmed Chenna
- Monogram Biosciences, Inc., Labcorp, South San Francisco, California, USA
| | - John W. Winslow
- Monogram Biosciences, Inc., Labcorp, South San Francisco, California, USA
| | | | | | - Haimanot Wasse
- Department of Internal Medicine, Rush University, Chicago, Illinois, USA
| | | | - Qin Liu
- The Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Ali Keshavarzian
- Department of Internal Medicine, Rush University, Chicago, Illinois, USA
- Rush Center for Integrated Microbiome and Chronobiology Research, Rush University, Chicago, Illinois, USA
| | - Alan Landay
- Department of Internal Medicine, Rush University, Chicago, Illinois, USA
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Sadrekarimi H, Gardanova ZR, Bakhshesh M, Ebrahimzadeh F, Yaseri AF, Thangavelu L, Hasanpoor Z, Zadeh FA, Kahrizi MS. Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora. Lab Invest 2022; 20:301. [PMID: 35794566 PMCID: PMC9258144 DOI: 10.1186/s12967-022-03492-7] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022]
Abstract
In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches’ therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.
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Stella GM, Scialò F, Bortolotto C, Agustoni F, Sanci V, Saddi J, Casali L, Corsico AG, Bianco A. Pragmatic Expectancy on Microbiota and Non-Small Cell Lung Cancer: A Narrative Review. Cancers (Basel) 2022; 14:cancers14133131. [PMID: 35804901 PMCID: PMC9264919 DOI: 10.3390/cancers14133131] [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: 05/05/2022] [Revised: 06/08/2022] [Accepted: 06/21/2022] [Indexed: 11/16/2022] Open
Abstract
It is well known that lung cancer relies on a number of genes aberrantly expressed because of somatic lesions. Indeed, the lungs, based on their anatomical features, are organs at a high risk of development of extremely heterogeneous tumors due to the exposure to several environmental toxic agents. In this context, the microbiome identifies the whole assemblage of microorganisms present in the lungs, as well as in distant organs, together with their structural elements and metabolites, which actively interact with normal and transformed cells. A relevant amount of data suggest that the microbiota plays a role not only in cancer disease predisposition and risk but also in its initiation and progression, with an impact on patients’ prognosis. Here, we discuss the mechanistic insights of the complex interaction between lung cancer and microbiota as a relevant component of the microenvironment, mainly focusing on novel diagnostic and therapeutic objectives.
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Affiliation(s)
- Giulia Maria Stella
- Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy; (V.S.); (A.G.C.)
- Unit of Respiratory Diseases IRCCS Policlinico San Matteo Foundation, Department of Medical Sciences and Infective Diseases, 27100 Pavia, Italy
- Correspondence:
| | - Filippo Scialò
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (F.S.); (A.B.)
- Ceinge Biotecnologie Avanzate s.c.a.r.l., 80145 Naples, Italy
| | - Chandra Bortolotto
- Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia Medical School, 27100 Pavia, Italy;
- Unit of Radiology, Department of Intensive Medicine, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy
| | - Francesco Agustoni
- Unit of Oncology, Department of Medical Sciences and Infective Diseases, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy;
| | - Vincenzo Sanci
- Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy; (V.S.); (A.G.C.)
- Unit of Respiratory Diseases IRCCS Policlinico San Matteo Foundation, Department of Medical Sciences and Infective Diseases, 27100 Pavia, Italy
| | - Jessica Saddi
- Radiation Therapy IRCCS Unit, Department of Medical Sciences and Infective Diseases, Policlinico San Matteo Foundation, 27100 Pavia, Italy;
- University of Milano-Bicocca, 20900 Monza, Italy
| | - Lucio Casali
- Honorary Consultant Student Support and Services, University of Pavia, 27100 Pavia, Italy;
| | - Angelo Guido Corsico
- Department of Internal Medicine and Medical Therapeutics, University of Pavia Medical School, 27100 Pavia, Italy; (V.S.); (A.G.C.)
- Unit of Respiratory Diseases IRCCS Policlinico San Matteo Foundation, Department of Medical Sciences and Infective Diseases, 27100 Pavia, Italy
| | - Andrea Bianco
- Department of Translational Medical Sciences, University of Campania “L. Vanvitelli”, 80138 Naples, Italy; (F.S.); (A.B.)
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Mahoney DE, Chalise P, Rahman F, Pierce JD. Influences of Gastrointestinal Microbiota Dysbiosis on Serum Proinflammatory Markers in Epithelial Ovarian Cancer Development and Progression. Cancers (Basel) 2022; 14:3022. [PMID: 35740687 PMCID: PMC9220985 DOI: 10.3390/cancers14123022] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/16/2022] [Accepted: 06/17/2022] [Indexed: 01/27/2023] Open
Abstract
GI microbiota has been implicated in producing the inflammatory tumor microenvironment of several cancers. Women with ovarian cancer often report GI-related symptoms at diagnosis although minimal is known about the possible GI bacteria that may trigger pro-tumorigenic immune responses in early EOC. The purpose of this study was to investigate the influences of GI microbiota dysbiosis on serum inflammatory markers during EOC utilizing a rodent model. This experimental design consisted of C57BL/6 mice randomly assigned to either the microbiota dysbiosis group (n = 6) or control group (n = 5). The CD7BL/6 mice assigned to the microbiota dysbiosis group were administered a mixture of broad-spectrum antibiotics (bacitracin and neomycin) for 2 weeks. Both groups were injected intraperitoneally with mouse ovarian epithelial cells that induce ovarian tumorigenesis. Levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were assessed in the serum, and the composition of the GI microbiota in fecal samples was measured using 16S rRNA gene sequencing. Overall CRP serum levels were significantly lower and TNFα levels were significantly higher in the microbiota dysbiosis group compared to the control group. The abundances of microbiota that correlated with CRP serum levels in the combined groups were genus Parabacteroides, Roseburia, and Emergencia and species Ruminococcus faecis, Parabacteroides distasonis, Roseburia Faecis, and Emergencia timonensis. This study provides evidence to support for further investigation of the GI microbial profiles in patients at risk of EOC.
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Affiliation(s)
- Diane E. Mahoney
- School of Nursing, University of Kansas Medical Center, Kansas City, KS 66160, USA;
| | - Prabhakar Chalise
- Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS 66160, USA;
| | - Faith Rahman
- Clinical Trials Clinical Operations, University of Kansas Cancer Center, Kansas City, KS 66160, USA;
| | - Janet D. Pierce
- School of Nursing, University of Kansas Medical Center, Kansas City, KS 66160, USA;
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Li Z, Liu Y, Zhang L. Role of the microbiome in oral cancer occurrence, progression and therapy. Microb Pathog 2022; 169:105638. [PMID: 35718272 DOI: 10.1016/j.micpath.2022.105638] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 06/07/2022] [Accepted: 06/10/2022] [Indexed: 02/07/2023]
Abstract
The oral cavity, like other digestive or mucosal sites, contains a site-specific microbiome that plays a significant role in maintaining health and homeostasis. Strictly speaking, the gastrointestinal tract starts from the oral cavity, with special attention paid to the specific flora of the oral cavity. In healthy people, the microbiome of the oral microenvironment is governed by beneficial bacteria, that benefit the host by symbiosis. When a microecological imbalance occurs, changes in immune and metabolic signals affect the characteristics of cancer, as well as chronic inflammation, disruption of the epithelial barrier, changes in cell proliferation and cell apoptosis, genomic instability, angiogenesis, and epithelial barrier destruction and metabolic regulation. These pathophysiological changes could result in oral cancer. Rising evidence suggests that oral dysbacteriosis and particular microbes may play a positive role in the evolution, development, progression, and metastasis of oral cancer, for instance, oral squamous cell carcinoma (OSCC) through direct or indirect action.
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Affiliation(s)
- Zhengrui Li
- Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200000, China.
| | - Yuan Liu
- Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200000, China.
| | - Ling Zhang
- Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200000, China.
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Cardeña-Gutiérrez A, López Barahona M. Predictive Biomarkers of Severe Immune-Related Adverse Events With Immune Checkpoint Inhibitors: Prevention, Underlying Causes, Intensity, and Consequences. Front Med (Lausanne) 2022; 9:908752. [PMID: 35774996 PMCID: PMC9237384 DOI: 10.3389/fmed.2022.908752] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/11/2022] [Indexed: 11/13/2022] Open
Abstract
Immune checkpoint inhibitors (ICIs) have dramatically transformed oncology by prolonging overall survival and yielding better patient tolerance compared to other chemotherapeutic agents. However, numerous questions remain unanswered about the toxicity profile of ICIs, its relationship with the treatment response, and causes underlying the excellent treatment response in some patients, while recalcitrance in others. Research groups have continued to seek biomarkers that may permit the identification of treatment responders and predict toxicity to facilitate cessation of immunotherapy before the development of severe toxicity. However, some studies have found associations between serious adverse events and longer survivorship. The research question entailed determining whether a biomarker is needed to predict severe immune-related adverse events prior to their development or whether providing early treatment for toxicity would inhibit the immune system from attaining a long-lasting anti-tumor effect. Therefore, this review conducted an in-depth analysis into the molecular basis of these observations.
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Affiliation(s)
- Ana Cardeña-Gutiérrez
- MedicalOncologyDepartment, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
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40
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DiMaio D, Emu B, Goodman AL, Mothes W, Justice A. Cancer Microbiology. J Natl Cancer Inst 2022; 114:651-663. [PMID: 34850062 PMCID: PMC9086797 DOI: 10.1093/jnci/djab212] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/18/2021] [Accepted: 11/15/2021] [Indexed: 12/12/2022] Open
Abstract
Microbes play important roles in cancer from direct carcinogenic effects to their use in treatment. Cancers caused by microorganisms account for approximately 15% of cancers, primarily in low- and middle-income countries. Unique features of infectious carcinogens include their transmissibility, mutability, and specific immune interactions, which provide challenges and opportunities for cancer prevention and treatment. For these agents, infection control through exposure reduction, antivirals, antibiotics, and vaccines is cancer control. In addition, developing evidence suggests that microorganisms including the human microbiome can indirectly modulate cancer formation and influence the effectiveness and toxicity of cancer treatments. Finally, microorganisms themselves can be used to prevent or treat cancer. The convergence of these factors signals the emergence of a new field, cancer microbiology. Recognition of cancer microbiology will spur research, stimulate cross-disciplinary training, inform drug development, and improve public health.
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Affiliation(s)
- Daniel DiMaio
- Department of Genetics, Yale School of Medicine, New Haven, CT, USA
- Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, USA
- Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA
- Yale Cancer Center, New Haven, CT, USA
| | - Brinda Emu
- Yale Cancer Center, New Haven, CT, USA
- Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA
| | - Andrew L Goodman
- Yale Cancer Center, New Haven, CT, USA
- Department of Microbial Pathogenesis, Yale University, New Haven, CT, USA
| | - Walther Mothes
- Yale Cancer Center, New Haven, CT, USA
- Department of Microbial Pathogenesis, Yale University, New Haven, CT, USA
| | - Amy Justice
- Yale Cancer Center, New Haven, CT, USA
- Department of General Medicine, Yale University, VA Medical Center, New Haven, CT, USA
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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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Ulusan Bagci O, Caner A. The interaction of gut microbiota with parasitic protozoa. J Parasit Dis 2022; 46:8-11. [PMID: 35299914 PMCID: PMC8901934 DOI: 10.1007/s12639-021-01443-5] [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: 03/31/2021] [Accepted: 08/17/2021] [Indexed: 10/20/2022] Open
Abstract
The human intestinal microbiota is composed of a complex combination of microorganisms including bacteria, virus, and eukaryotes. The microbiota plays a critical role in homeostasis through creating a mucosal barrier, providing protective responses to pathogens, and affecting the immune system and metabolism of the host. Molecules secreted by parasites can alter composition of microbiota both by acting directly on the microbial community and indirectly by affecting the host physiology. On the other hand, the microbiota composition can affect the survival, physiology, and virulence of many parasitic protozoa. Explanation of possible interactions between the microbiota, immune response, and protozoa may further clarify the underlying mechanisms of infectivity, clinical variations, and life-cycle of protozoa.
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Affiliation(s)
- Ozlem Ulusan Bagci
- grid.8302.90000 0001 1092 2592Department of Parasitology, Faculty of Medicine, Ege University Medical School, 35100 Bornova, Izmir, Turkey
| | - Ayse Caner
- grid.8302.90000 0001 1092 2592Department of Parasitology, Faculty of Medicine, Ege University Medical School, 35100 Bornova, Izmir, Turkey ,grid.8302.90000 0001 1092 2592Cancer Research Center, Ege University, Izmir, Turkey ,grid.240145.60000 0001 2291 4776Departments of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX USA
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Merali N, Chouari T, Kayani K, Rayner CJ, Jiménez JI, Krell J, Giovannetti E, Bagwan I, Relph K, Rockall TA, Dhillon T, Pandha H, Annels NE, Frampton AE. A Comprehensive Review of the Current and Future Role of the Microbiome in Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2022; 14:1020. [PMID: 35205769 PMCID: PMC8870349 DOI: 10.3390/cancers14041020] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/11/2022] [Accepted: 02/15/2022] [Indexed: 02/07/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second most common cause of cancer death in the USA by 2030, yet progress continues to lag behind that of other cancers, with only 9% of patients surviving beyond 5 years. Long-term survivorship of PDAC and improving survival has, until recently, escaped our understanding. One recent frontier in the cancer field is the microbiome. The microbiome collectively refers to the extensive community of bacteria and fungi that colonise us. It is estimated that there is one to ten prokaryotic cells for each human somatic cell, yet, the significance of this community in health and disease has, until recently, been overlooked. This review examines the role of the microbiome in PDAC and how it may alter survival outcomes. We evaluate the possibility of employing microbiomic signatures as biomarkers of PDAC. Ultimately this review analyses whether the microbiome may be amenable to targeting and consequently altering the natural history of PDAC.
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Affiliation(s)
- Nabeel Merali
- Minimal Access Therapy Training Unit (MATTU), Leggett Building, University of Surrey, Daphne Jackson Road, Guildford GU2 7WG, UK; (N.M.); (T.A.R.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK; (T.C.); (K.K.); (C.J.R.)
- Targeted Cancer Therapy Unit, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK; (I.B.); (K.R.); (T.D.); (H.P.); (N.E.A.)
| | - Tarak Chouari
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK; (T.C.); (K.K.); (C.J.R.)
- Targeted Cancer Therapy Unit, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK; (I.B.); (K.R.); (T.D.); (H.P.); (N.E.A.)
| | - Kayani Kayani
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK; (T.C.); (K.K.); (C.J.R.)
- Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
| | - Charles J. Rayner
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK; (T.C.); (K.K.); (C.J.R.)
- Targeted Cancer Therapy Unit, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK; (I.B.); (K.R.); (T.D.); (H.P.); (N.E.A.)
| | - José I. Jiménez
- Department of Life Sciences, South Kensington Campus, Imperial College London, London SW7 2AZ, UK;
| | - Jonathan Krell
- Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK;
| | - Elisa Giovannetti
- Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands;
- Fondazione Pisa per la Scienza, 56017 San Giuliano, Italy
| | - Izhar Bagwan
- Targeted Cancer Therapy Unit, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK; (I.B.); (K.R.); (T.D.); (H.P.); (N.E.A.)
| | - Kate Relph
- Targeted Cancer Therapy Unit, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK; (I.B.); (K.R.); (T.D.); (H.P.); (N.E.A.)
| | - Timothy A. Rockall
- Minimal Access Therapy Training Unit (MATTU), Leggett Building, University of Surrey, Daphne Jackson Road, Guildford GU2 7WG, UK; (N.M.); (T.A.R.)
| | - Tony Dhillon
- Targeted Cancer Therapy Unit, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK; (I.B.); (K.R.); (T.D.); (H.P.); (N.E.A.)
| | - Hardev Pandha
- Targeted Cancer Therapy Unit, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK; (I.B.); (K.R.); (T.D.); (H.P.); (N.E.A.)
| | - Nicola E. Annels
- Targeted Cancer Therapy Unit, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK; (I.B.); (K.R.); (T.D.); (H.P.); (N.E.A.)
| | - Adam E. Frampton
- Minimal Access Therapy Training Unit (MATTU), Leggett Building, University of Surrey, Daphne Jackson Road, Guildford GU2 7WG, UK; (N.M.); (T.A.R.)
- Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital, Egerton Road, Guildford GU2 7XX, UK; (T.C.); (K.K.); (C.J.R.)
- Targeted Cancer Therapy Unit, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK; (I.B.); (K.R.); (T.D.); (H.P.); (N.E.A.)
- Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK;
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Tortora SC, Bodiwala VM, Quinn A, Martello LA, Vignesh S. Microbiome and colorectal carcinogenesis: Linked mechanisms and racial differences. World J Gastrointest Oncol 2022; 14:375-395. [PMID: 35317317 PMCID: PMC8918999 DOI: 10.4251/wjgo.v14.i2.375] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/26/2021] [Accepted: 01/14/2022] [Indexed: 02/06/2023] Open
Abstract
Various studies have shown the interplay between the intestinal microbiome, environmental factors, and genetic changes in colorectal cancer (CRC) development. In this review, we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas, and their proposed molecular mechanisms in relation to the processes of “the hallmarks of cancer”, and differences in microbial diversity and abundance between race/ethnicity. Patients with CRC showed increased levels of Bacteroides, Prevotella, Escherichia coli, enterotoxigenic Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis, Fusobacterium nucleatum (F. nucleatum) and Clostridium difficile. Higher levels of Bacteroides have been found in African American (AA) compared to Caucasian American (CA) patients. Pro-inflammatory bacteria such as F. nucleatum and Enterobacter species were significantly higher in AAs. Also, AA patients have been shown to have decreased microbial diversity compared to CA patients. Some studies have shown that using microbiome profiles in conjunction with certain risk factors such as age, race and body mass index may help predict healthy colon vs one with adenomas or carcinomas. Periodontitis is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic Whites. This condition causes increased systemic inflammation, immune dysregulation, gut microbiota dysbiosis and thereby possibly influencing colorectal carcinogenesis. Periodontal-associated bacteria such as Fusobacterium, Prevotella, Bacteroides and Porphyromonas have been found in CRC tissues and in feces of CRC patients. Therefore, a deeper understanding of the association between oral and gastrointestinal bacterial profile, in addition to identifying prevalent bacteria in patients with CRC and the differences observed in ethnicity/race, may play a pivotal role in predicting incidence, prognosis, and lead to the development of new treatments.
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Affiliation(s)
- Sofia C Tortora
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Vimal M Bodiwala
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Andrew Quinn
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Laura A Martello
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Shivakumar Vignesh
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
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45
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Multi-Omic Approaches in Colorectal Cancer beyond Genomic Data. J Pers Med 2022; 12:jpm12020128. [PMID: 35207616 PMCID: PMC8880341 DOI: 10.3390/jpm12020128] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/10/2022] [Accepted: 01/12/2022] [Indexed: 02/04/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most frequent tumours and one of the major causes of morbidity and mortality globally. Its incidence has increased in recent years and could be linked to unhealthy dietary habits combined with environmental and hereditary factors, which can lead to genetic and epigenetic changes and induce tumour development. The model of CRC progression has always been based on a genomic, parametric, static and complex approach involving oncogenes and tumour suppressor genes. Recent advances in omics sciences have sought a paradigm shift to a multiparametric, immunological-stromal, and dynamic approach for a better understanding of carcinogenesis and tumour heterogeneity. In the present paper, we review the most important preclinical and clinical data and present recent discoveries in the field of transcriptomics, proteomics, metagenomics and radiomics in CRC disease.
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Khan I. Microbiome. Indian J Med Paediatr Oncol 2021. [DOI: 10.1055/s-0041-1735599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Imran Khan
- Department of Medical Oncology, Artemis Hospitals, Gurugram, Haryana, India
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McIlvanna E, Linden GJ, Craig SG, Lundy FT, James JA. Fusobacterium nucleatum and oral cancer: a critical review. BMC Cancer 2021; 21:1212. [PMID: 34774023 PMCID: PMC8590362 DOI: 10.1186/s12885-021-08903-4] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 10/21/2021] [Indexed: 02/07/2023] Open
Abstract
There is a growing level of interest in the potential role inflammation has on the initiation and progression of malignancy. Notable examples include Helicobacter pylori-mediated inflammation in gastric cancer and more recently Fusobacterium nucleatum-mediated inflammation in colorectal cancer. Fusobacterium nucleatum is a Gram-negative anaerobic bacterium that was first isolated from the oral cavity and identified as a periodontal pathogen. Biofilms on oral squamous cell carcinomas are enriched with anaerobic periodontal pathogens, including F. nucleatum, which has prompted hypotheses that this bacterium could contribute to oral cancer development. Recent studies have demonstrated that F. nucleatum can promote cancer by several mechanisms; activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation and immune evasion. This review provides an update on the association between F. nucleatum and oral carcinogenesis, and provides insights into the possible mechanisms underlying it.
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Affiliation(s)
- Emily McIlvanna
- Patrick G Johnson Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Gerard J Linden
- Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Stephanie G Craig
- Patrick G Johnson Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, UK.,Precision Medicine Centre of Excellence, Health Sciences Building, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Fionnuala T Lundy
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.
| | - Jacqueline A James
- Patrick G Johnson Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, UK. .,Precision Medicine Centre of Excellence, Health Sciences Building, Queen's University Belfast, Belfast, Northern Ireland, UK. .,Northern Ireland Biobank, Health Sciences Building, Queen's University Belfast, Belfast, Northern Ireland, UK.
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48
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Amatya SB, Salmi S, Kainulainen V, Karihtala P, Reunanen J. Bacterial Extracellular Vesicles in Gastrointestinal Tract Cancer: An Unexplored Territory. Cancers (Basel) 2021; 13:5450. [PMID: 34771614 PMCID: PMC8582403 DOI: 10.3390/cancers13215450] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 10/19/2021] [Indexed: 12/17/2022] Open
Abstract
Bacterial extracellular vesicles are membrane-enclosed, lipid bi-layer nanostructures that carry different classes of biomolecules, such as nucleic acids, lipids, proteins, and diverse types of small molecular metabolites, as their cargo. Almost all of the bacteria in the gut secrete extracellular vesicles to assist them in competition, survival, material exchange, host immune modulation, infection, and invasion. The role of gut microbiota in the development, progression, and pathogenesis of gastrointestinal tract (GIT) cancer has been well documented. However, the possible involvement of bacterial extracellular vesicles (bEVs) in GIT cancer pathophysiology has not been given due attention. Studies have illustrated the ability of bEVs to cross physiological barriers, selectively accumulate near tumor cells, and possibly alter the tumor microenvironment (TME). A systematic search of original published works related to bacterial extracellular vesicles on gastrointestinal cancer was performed for this review. The current systemic review outlines the possible impact of gut microbiota derived bEVs in GIT cancer in light of present-day understanding. The necessity of using advanced sequencing technologies, such as genetic, proteomic, and metabolomic investigation methodologies, to facilitate an understanding of the interrelationship between cancer-associated bacterial vesicles and gastrointestinal cancer is also emphasized. We further discuss the clinical and pharmaceutical potential of bEVs, along with future efforts needed to understand the mechanism of interaction of bEVs in GIT cancer pathogenesis.
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Affiliation(s)
- Sajeen Bahadur Amatya
- Biocenter Oulu & Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland; (S.B.A.); (S.S.)
| | - Sonja Salmi
- Biocenter Oulu & Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland; (S.B.A.); (S.S.)
| | - Veera Kainulainen
- Human Microbiome Research Program Unit, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland;
| | - Peeter Karihtala
- Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, 00290 Helsinki, Finland;
| | - Justus Reunanen
- Biocenter Oulu & Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland; (S.B.A.); (S.S.)
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Lythgoe MP, Ghani R, Mullish BH, Marchesi JR, Krell J. The potential of fecal microbiota transplantation in oncology. Trends Microbiol 2021; 30:10-12. [PMID: 34711461 DOI: 10.1016/j.tim.2021.10.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 10/07/2021] [Accepted: 10/08/2021] [Indexed: 01/01/2023]
Abstract
Immune checkpoint inhibitors (ICPIs) are efficacious treatments for several cancers. However, most patients fail to demonstrate durable complete responses. The gut microbiome composition influences the ICPI response. Two recent proof-of-concept studies have demonstrated the utility of fecal microbiota transplantation to transform ICPI responsiveness in refractory patients, providing intriguing evidence for the future of microbiota modulation within oncology.
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Affiliation(s)
- Mark P Lythgoe
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK.
| | - Rohma Ghani
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary's Hospital Campus, Imperial College London, London, UK
| | - Benjamin H Mullish
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary's Hospital Campus, Imperial College London, London, UK
| | - Julian R Marchesi
- Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, St Mary's Hospital Campus, Imperial College London, London, UK
| | - Jonathan Krell
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK
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Le Noci V, Bernardo G, Bianchi F, Tagliabue E, Sommariva M, Sfondrini L. Toll Like Receptors as Sensors of the Tumor Microbial Dysbiosis: Implications in Cancer Progression. Front Cell Dev Biol 2021; 9:732192. [PMID: 34604233 PMCID: PMC8485072 DOI: 10.3389/fcell.2021.732192] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 08/23/2021] [Indexed: 01/02/2023] Open
Abstract
The microbiota is a complex ecosystem of active microorganisms resident in the body of mammals. Although the majority of these microorganisms resides in the distal gastrointestinal tract, high-throughput DNA sequencing technology has made possible to understand that several other tissues of the human body host their own microbiota, even those once considered sterile, such as lung tissue. These bacterial communities have important functions in maintaining a healthy body state, preserving symbiosis with the host immune system, which generates protective responses against pathogens and regulatory pathways that sustain the tolerance to commensal microbes. Toll-like receptors (TLRs) are critical in sensing the microbiota, maintaining the tolerance or triggering an immune response through the direct recognition of ligands derived from commensal microbiota or pathogenic microbes. Lately, it has been highlighted that the resident microbiota influences the initiation and development of cancer and its response to therapies and that specific changes in the number and distribution of taxa correlate with the existence of cancers in various tissues. However, the knowledge of functional activity and the meaning of microbiome changes remain limited. This review summarizes the current findings on the function of TLRs as sensors of the microbiota and highlighted their modulation as a reflection of tumor-associated changes in commensal microbiota. The data available to date suggest that commensal "onco-microbes" might be able to break the tolerance of TLRs and become complicit in cancer by sustaining its growth.
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Affiliation(s)
- Valentino Le Noci
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
| | - Giancarla Bernardo
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
| | - Francesca Bianchi
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
- U.O. Laboratorio di Morfologia Umana Applicata, IRCCS Policlinico San Donato, Milan, Italy
| | - Elda Tagliabue
- Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Michele Sommariva
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
- Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Lucia Sfondrini
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy
- Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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