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Greco L, Rubbino F, Ferrari C, Cameletti M, Grizzi F, Bonelli F, Malesci A, Mazzone M, Ricciardiello L, Laghi L. Association of Fusobacterium nucleatum with colorectal cancer molecular subtypes and its outcome: a systematic review. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2025; 6:e5. [PMID: 40297307 PMCID: PMC12035788 DOI: 10.1017/gmb.2025.3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 03/27/2025] [Accepted: 03/28/2025] [Indexed: 04/30/2025]
Abstract
Colorectal cancer (CRC) represents a relevant public health problem, with high incidence and mortality in Western countries. CRC can occur as sporadic (65%-75%), common familial (25%), or as a consequence of an inherited predisposition (up to 10%). While unravelling its genetic basis has been a long trip leading to relevant clinical implementation over more than 30 years, other contributing factors remain to be clarified. Among these, micro-organisms have emerged as critical players in the development and progression of the disease, as well as for CRC treatment response. Fusobacterium nucleatum (Fn) has been associated with CRC development in both pre-clinical models and clinical settings. Fusobacteria are core members of the human oral microbiome, while being less prevalent in the healthy gut, prompting questions about their localization in CRC and its precursor lesions. This review aims to critically discuss the evidence connecting Fn with CRC pathogenesis, its molecular subtypes and clinical outcomes.
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Affiliation(s)
- Luana Greco
- Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Federica Rubbino
- Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Clarissa Ferrari
- Research and Clinical Trials Office, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
| | | | - Fabio Grizzi
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital, Milan, Italy
| | | | | | - Massimiliano Mazzone
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Macrophage Dynamics Lab, IRCCS Humanitas Research Hospital, Milan, Italy
- Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium
- Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium
| | - Luigi Ricciardiello
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas at MD Anderson Cancer Center, Houston, TX, USA
| | - Luigi Laghi
- Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
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2
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Mondal T, Chattopadhyay D, Saha Mondal P, Das S, Mondal A, Das A, Samanta S, Saha T. Fusobacterium nucleatum modulates the Wnt/β-catenin pathway in colorectal cancer development. Int J Biol Macromol 2025; 299:140196. [PMID: 39848378 DOI: 10.1016/j.ijbiomac.2025.140196] [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: 10/01/2024] [Revised: 01/18/2025] [Accepted: 01/20/2025] [Indexed: 01/25/2025]
Abstract
The Wnt/β-catenin signalling pathway normally maintains cellular and tissue homeostasis by regulating cellular differentiation and survival in a controlled manner. An aberrantly regulated Wnt/β-catenin signalling pathway can transform into an oncogenic pathway, which is associated with Colorectal cancer (CRC) as well as other cancers. CRC is one of the most frequently occurring gastrointestinal cancers worldwide. In CRC tissues, deregulation of Wnt/β-catenin pathway is observed, which indicates that this oncogenic pathway directly promotes CRC malignancy, cell migration, angiogenesis, chemoresistance, as well as shorter lifespan of a patient. Growing evidence suggests that human commensal microbes have a strong association with carcinogenesis, particularly the prevalence and high enrichment of Fusobacterium nucleatum in CRC progression. The Wnt/β-catenin pathway is one of the targeted pathways by F. nucleatum in CRC, where Fusobacterium adhesin attaches to E-cadherin to initiate infection. Also, Wnt/β-catenin pathway can be a potential target for the treatment of both CRC and F. nucleatum-positive CRC. Here, we discuss the underlying mechanisms of F. nucleatum-positive CRC development through modulation of Wnt/β-catenin signalling and its possibility for the application in targeted therapy of F. nucleatum-positive CRC.
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Affiliation(s)
- Tanushree Mondal
- Department of Molecular Biology and Biotechnology, University of Kalyani, Kalyani 741235, Nadia, West Bengal, India
| | - Deepanjan Chattopadhyay
- Department of Molecular Biology and Biotechnology, University of Kalyani, Kalyani 741235, Nadia, West Bengal, India
| | - Paromita Saha Mondal
- Department of Molecular Biology and Biotechnology, University of Kalyani, Kalyani 741235, Nadia, West Bengal, India
| | - Sanjib Das
- Department of Molecular Biology and Biotechnology, University of Kalyani, Kalyani 741235, Nadia, West Bengal, India
| | - Amalesh Mondal
- Department of Molecular Biology and Biotechnology, University of Kalyani, Kalyani 741235, Nadia, West Bengal, India; Department of Physiology, Katwa Collage, Katwa, Purba Bardhaman, West Bengal 713130, India
| | - Abhishek Das
- Department of Molecular Biology and Biotechnology, University of Kalyani, Kalyani 741235, Nadia, West Bengal, India
| | - Subhasree Samanta
- Department of Molecular Biology and Biotechnology, University of Kalyani, Kalyani 741235, Nadia, West Bengal, India
| | - Tanima Saha
- Department of Molecular Biology and Biotechnology, University of Kalyani, Kalyani 741235, Nadia, West Bengal, India.
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3
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Zhang X, Chen Y, Xia Y, Lin S, Zhou X, Pang X, Yu J, Sun L. Oral microbiota in colorectal cancer: Unraveling mechanisms and application potential. Life Sci 2025; 365:123462. [PMID: 39947314 DOI: 10.1016/j.lfs.2025.123462] [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: 10/22/2024] [Revised: 01/31/2025] [Accepted: 02/10/2025] [Indexed: 02/17/2025]
Abstract
Colorectal cancer (CRC), with a rising prevalence, is the third most commonly diagnosed cancer and the third leading cause of cancer-related death. Studies have shown that a complex interplay between the development of CRC and alterations in the oral microbiome. Recent advancements in genomics and metagenomics have highlighted the significant roles of certain oral microbes, particularly Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum), in the progression of CRC. However, the detailed mechanisms by which the oral microbiota influence CRC development remain unclear. This review aims to elucidate the role of oral microbiota in CRC progression, evaluate their potential as biomarkers, and explore therapeutic strategies targeting these microbes. This review offers insights into the mechanisms underlying the interaction between oral microbiota and CRC, underscoring the potential of oral microbes as diagnostic and prognostic biomarkers, as well as therapeutic targets. Future research should focus on clarifying the exact pathways and developing innovative therapeutic strategies to enhance the diagnosis and treatment.
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Affiliation(s)
- Xinran Zhang
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China
| | - Yixin Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China
| | - Yuwei Xia
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China
| | - Shenghao Lin
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China
| | - Xinlei Zhou
- The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Xi Pang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
| | - Jieru Yu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
| | - Leitao Sun
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China; Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
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4
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Sun J, Song S, Liu J, Chen F, Li X, Wu G. Gut microbiota as a new target for anticancer therapy: from mechanism to means of regulation. NPJ Biofilms Microbiomes 2025; 11:43. [PMID: 40069181 PMCID: PMC11897378 DOI: 10.1038/s41522-025-00678-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 03/04/2025] [Indexed: 03/15/2025] Open
Abstract
In order to decipher the relationship between gut microbiota imbalance and cancer, this paper reviewed the role of intestinal microbiota in anticancer therapy and related mechanisms, discussed the current research status of gut microbiota as a biomarker of cancer, and finally summarized the reasonable means of regulating gut microbiota to assist cancer therapy. Overall, our study reveals that the gut microbiota can serve as a potential target for improving cancer management.
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Affiliation(s)
- Jiaao Sun
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Shiyan Song
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jiahua Liu
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Feng Chen
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
| | - Xiaorui Li
- Department of oncology, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
| | - Guangzhen Wu
- Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
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5
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Mukherjee S, Chopra A, Karmakar S, Bhat SG. Periodontitis increases the risk of gastrointestinal dysfunction: an update on the plausible pathogenic molecular mechanisms. Crit Rev Microbiol 2025; 51:187-217. [PMID: 38602474 DOI: 10.1080/1040841x.2024.2339260] [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: 11/04/2023] [Revised: 02/28/2024] [Accepted: 04/01/2024] [Indexed: 04/12/2024]
Abstract
Periodontitis is an immuno-inflammatory disease of the soft tissues surrounding the teeth. Periodontitis is linked to many communicable and non-communicable diseases such as diabetes, cardiovascular disease, rheumatoid arthritis, and cancers. The oral-systemic link between periodontal disease and systemic diseases is attributed to the spread of inflammation, microbial products and microbes to distant organ systems. Oral bacteria reach the gut via swallowed saliva, whereby they induce gut dysbiosis and gastrointestinal dysfunctions. Some periodontal pathogens like Porphyromonas. gingivalis, Klebsiella, Helicobacter. Pylori, Streptococcus, Veillonella, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus, Haemophilus, Aggregatibacter actinomycetomcommitans and Streptococcus mutans can withstand the unfavorable acidic, survive in the gut and result in gut dysbiosis. Gut dysbiosis increases gut inflammation, and induce dysplastic changes that lead to gut dysfunction. Various studies have linked oral bacteria, and oral-gut axis to various GIT disorders like inflammatory bowel disease, liver diseases, hepatocellular and pancreatic ductal carcinoma, ulcerative colitis, and Crohn's disease. Although the correlation between periodontitis and GIT disorders is well established, the intricate molecular mechanisms by which oral microflora induce these changes have not been discussed extensively. This review comprehensively discusses the intricate and unique molecular and immunological mechanisms by which periodontal pathogens can induce gut dysbiosis and dysfunction.
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Affiliation(s)
- Sayantan Mukherjee
- Department of Periodontology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Aditi Chopra
- Department of Periodontology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Shaswata Karmakar
- Department of Periodontology, Manipal College of Dental Sciences, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Subraya Giliyar Bhat
- Department of Preventive Dental Sciences, Division of Periodontology, College of Dental Surgery, Iman Abdulrahman Bin Faizal University, Dammam, Saudi Arabia
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Chiscuzzu F, Crescio C, Varrucciu S, Rizzo D, Sali M, Delogu G, Bussu F. Current Evidence on the Relation Between Microbiota and Oral Cancer-The Role of Fusobacterium nucleatum-A Narrative Review. Cancers (Basel) 2025; 17:171. [PMID: 39857953 PMCID: PMC11763498 DOI: 10.3390/cancers17020171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 12/30/2024] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
Oral squamous cell carcinoma (OSCC) is one the most prevalent head and neck cancers and represents a major cause of morbidity and mortality worldwide. The main established risk factors for OSCC include tobacco and alcohol consumption and betel quid chewing, which may contribute alone or in combination with other environmental factors to carcinogenesis. The oral microbiota is emerging as a key player in the establishment of the molecular and cellular mechanisms that may trigger or promote carcinogenesis, including in the oral cavity. Among the bacterial species found in the oral microbiota, Fusobacterium nucleatum, an anaerobic bacterium commonly found in oral biofilms and a periodontal pathogen, has gained attention due to solid evidence implicating F. nucleatum in colorectal cancer (CRC). F. nucleatum has been shown to induce chronic inflammation, promote cell proliferation and trigger cellular invasion while deploying immune evasion mechanisms. These experimental findings were first obtained in in vitro and in vivo models of CRC and are being confirmed in studies on OSCC. In this review, we summarize the most recent findings on the role of F. nucleatum in OSCC, discuss the clinical implications in terms of prognosis and provide an overview of the key mechanisms involved. Moreover, we identify research questions and aspects that require investigations to clarify the role of F. nucleatum in OSCC. We anticipate that studies in this emerging field may have a significant clinical impact on the diagnosis, prognosis and management of OSCC.
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Affiliation(s)
| | - Claudia Crescio
- Otolaryngology Division, Azienda Ospedaliera Universitaria di Sassari, 07100 Sassari, Italy; (D.R.); (F.B.)
| | - Simona Varrucciu
- Department of Medicine Surgery and Pharmacy, Sassari University, 07100 Sassari, Italy;
| | - Davide Rizzo
- Otolaryngology Division, Azienda Ospedaliera Universitaria di Sassari, 07100 Sassari, Italy; (D.R.); (F.B.)
- Department of Medicine Surgery and Pharmacy, Sassari University, 07100 Sassari, Italy;
| | - Michela Sali
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie-Sezione di Microbiologia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
- Department of Laboratory and Infectivology Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Giovanni Delogu
- Mater Olbia Hospital, 07026 Olbia, Italy; (F.C.); (G.D.)
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie-Sezione di Microbiologia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Francesco Bussu
- Otolaryngology Division, Azienda Ospedaliera Universitaria di Sassari, 07100 Sassari, Italy; (D.R.); (F.B.)
- Department of Medicine Surgery and Pharmacy, Sassari University, 07100 Sassari, Italy;
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7
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Sahandi J, Sorgeloos P, Tang KW, Jafaryan H, Yang W, Mai K, Zhang W. Highlighting antibiotic-free aquaculture by using marine microbes as a sustainable method to suppress Vibrio and enhance the performance of brine shrimp (Artemia franciscana). Arch Microbiol 2025; 207:26. [PMID: 39776229 DOI: 10.1007/s00203-024-04234-7] [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: 11/07/2024] [Revised: 12/14/2024] [Accepted: 12/31/2024] [Indexed: 01/11/2025]
Abstract
Brine shrimp nauplii are widely used as live food in fish and shellfish aquaculture but they may transmit pathogenic Vibrio to the target species causing significant economic loss. Heavy usage of antibiotics is expensive and environmentally damaging. Use of natural microbes as probiotics for disease management is a more sustainable strategy. In this study the abilities of four marine microbes-Debaryomyces hansenii, Ruegeria mobilis, Lactobacillus plantarum and Bacillus subtilis-to suppress Vibrio spp. and promote growth performance and survival of brine shrimp (Artemia franciscana) were investigated. Nauplii (Instar II) were exposed to 108 CFU mL-1 of one of the four microbes; a control without added microbes was included for comparison. The nauplii were fed daily with the microalga Nannochloropsis oculata. Population change, survival, weight gain, length gain, enzyme activity, microbial retention and body biochemical composition of the brine shrimp were measured. The results showed that B. subtilis and L. plantarum significantly decreased the body loading of Vibrio spp. in A. franciscana. Survival rate, weight gain and length gain of (A) franciscana all increased in L. plantarum and (B) subtilis treatments, but the growth performance in the D. hansenii and R. mobilis treatments was less consistent. Higher lipase and protease activities and lower body ash content in the brine shrimp were observed in the B. subtilis and L. plantarum treatments (P < 0.05). The abundance of B. subtilis in the brine shrimp was relatively stable even after 8 days of starvation. These findings demonstrate that B. subtilis was the most promising probiotic among the tested species, especially for long-term application without the need for repeated inoculation.
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Affiliation(s)
- Javad Sahandi
- Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, 5 Yushan Road, 266003, Qingdao, P. R. China.
| | - Patrick Sorgeloos
- Lab of Aquaculture and Artemia Reference Center, Ghent University, Ghent, 9000, Belgium
| | - Kam W Tang
- Department of Life Sciences, Texas A&M University-Corpus Christi, Corpus Christi, TX78412, USA
| | - Hojatollah Jafaryan
- Department of Fisheries and Forestry, Faculty of Natural Resources, Gonbad Kavous University, Gonbad, 4971799151, Iran
| | - Wei Yang
- Institute of Evolution and Marine Bioaffiliationersity, KLMME, Ocean University of China, Qingdao, 266003, China
| | - Kangsen Mai
- Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, 5 Yushan Road, 266003, Qingdao, P. R. China
| | - Wenbing Zhang
- Key Laboratory of Aquaculture Nutrition and Feeds (Ministry of Agriculture and Rural Affairs), Key Laboratory of Mariculture (Ministry of Education), Fisheries College, Ocean University of China, 5 Yushan Road, 266003, Qingdao, P. R. China.
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8
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Ye C, Liu X, Liu Z, Pan C, Zhang X, Zhao Z, Sun H. Fusobacterium nucleatum in tumors: from tumorigenesis to tumor metastasis and tumor resistance. Cancer Biol Ther 2024; 25:2306676. [PMID: 38289287 PMCID: PMC10829845 DOI: 10.1080/15384047.2024.2306676] [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: 11/05/2023] [Accepted: 01/13/2024] [Indexed: 02/01/2024] Open
Abstract
Fusobacterium nucleatum, an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role in cancer progression and prognosis. While extensive research has revealed mechanistic links between Fusobacterium nucleatum and colorectal cancer, a comprehensive review spanning its presence and metastatic implications in cancers beyond colorectal origin is conspicuously absent. This paper broadens our perspective from colorectal cancer to various malignancies associated with Fusobacterium nucleatum, including oral, pancreatic, esophageal, breast, and gastric cancers. Our central focus is to unravel the mechanisms governing Fusobacterium nucleatum colonization, initiation, and promotion of metastasis across diverse cancer types. Additionally, we explore Fusobacterium nucleatum's adverse impacts on cancer therapies, particularly within the domains of immunotherapy and chemotherapy. Furthermore, this paper underscores the clinical research significance of Fusobacterium nucleatum as a potential tumor biomarker and therapeutic target, offering a novel outlook on its applicability in cancer detection and prognostic assessment.
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Affiliation(s)
- Chun Ye
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xiao Liu
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zilun Liu
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Chuxuan Pan
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xiaowei Zhang
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zhanyi Zhao
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Haitao Sun
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Laboratory Medicine, Central People’s Hospital of Ji’an, Shanghai East Hospital of Ji’an, Ji’an, China
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Ibeanu GC, Rowaiye AB, Okoli JC, Eze DU. Microbiome Differences in Colorectal Cancer Patients and Healthy Individuals: Implications for Vaccine Antigen Discovery. Immunotargets Ther 2024; 13:749-774. [PMID: 39698218 PMCID: PMC11652712 DOI: 10.2147/itt.s486731] [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: 07/26/2024] [Accepted: 12/02/2024] [Indexed: 12/20/2024] Open
Abstract
Background Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with numerous risk factors contributing to its development. Recent research has illuminated the significant role of the gut microbiota in CRC pathogenesis, identifying various microbial antigens as potential targets for vaccine development. Aim This review aimed at exploring the potential sources of microbial antigens that could be harnessed to create effective CRC vaccines and understand the role of microbiome-CRC interactions in carcinogenesis. Methods A comprehensive search of original research and review articles on the pathological links between key microbial candidates, particularly those more prevalent in CRC tissues, was conducted. This involved extensive use of the PubMed and Medline databases, as well as the Google Scholar search engine, utilizing pertinent keywords. A total of one hundred and forty-three relevant articles in English, mostly published between 2018 and 2024, were selected. Results Numerous microbes, particularly bacteria and viruses, are significantly overrepresented in CRC tissues and have been shown to promote tumorigenesis by inducing inflammation and modulating the immune system. This makes them promising candidates for antigens in the development of CRC vaccines. Conclusion The selection of microbial antigens focuses on their capacity to trigger a strong immune response and their link to tumor presence and progression. Identifying and validating these antigens through preclinical testing is essential in developing a CRC vaccine.
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Affiliation(s)
- Gordon C Ibeanu
- Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC, 27707, USA
| | - Adekunle B Rowaiye
- Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC, 27707, USA
- Department of Agricultural Biotechnology, National Biotechnology Development Agency, Abuja, Nigeria
| | - Joy C Okoli
- Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC, 27707, USA
| | - Daniel U Eze
- Department of Pharmaceutical Sciences, North Carolina Central University, Durham, NC, 27707, USA
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10
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Hong BY, Chhaya A, Robles A, Cervantes J, Tiwari S. The role of Fusobacterium nucleatum in the pathogenesis of colon cancer. J Investig Med 2024; 72:819-827. [PMID: 39175147 DOI: 10.1177/10815589241277829] [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] [Indexed: 08/24/2024]
Abstract
Previously, many studies have reported changes in the gut microbiota of patients with colorectal cancer (CRC). While CRC is a well-described disease, the relationship between its development and features of the intestinal microbiome is still being understood. Evidence linking Fusobacterium nucleatum enrichment in colorectal tumor tissue has prompted the elucidation of various molecular mechanisms and tumor-promoting attributes. In this review we highlight various aspects of our understanding of the relationship between the development of CRC and the alteration of intestinal microbiome, focusing specifically on the role of F. nucleatum. As the amount of F. nucleatum DNA in CRC tissue is associated with shorter survival, it may potentially serve as a prognostic biomarker, and most importantly may open the door for a role in CRC treatment.
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Affiliation(s)
- Bo-Young Hong
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Ajay Chhaya
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA
| | - Alejandro Robles
- Department of Internal Medicine, Division of Gastroenterology, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA
| | - Jorge Cervantes
- Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
| | - Sangeeta Tiwari
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA
- Biomedical Research Center, University of Texas at El Paso, El Paso, TX, USA
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11
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Nakao T, Shimada M, Yoshikawa K, Tokunaga T, Nishi M, Kashihara H, Takasu C, Wada Y, Yoshimoto T. Number of Healthy Teeth Can Predict the Response of Rectal Cancer to Chemoradiotherapy: A Retrospective Study. Am Surg 2024; 90:2679-2686. [PMID: 38636083 DOI: 10.1177/00031348241244628] [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] [Indexed: 04/20/2024]
Abstract
BACKGROUND It has been reported that the oral and gut microbiomes are associated with the prognosis in patients who undergo surgery, chemotherapy, and radiation for colorectal cancer. This study is the first to identify a correlation between the number of healthy teeth, which is an oral health indicator, and the efficacy of preoperative chemotherapy for rectal cancer. METHODS This retrospective single-center study included 30 patients who underwent radical surgery after preoperative chemoradiotherapy (CRT) between December 2013 and June 2021. The relationship between number of teeth before CRT and the efficacy of CRT, CRT-related adverse events, postoperative complications, and long-term postoperative outcomes was examined. RESULTS The number of healthy teeth was significantly greater in patients with downstaging of their disease than in those without downstaging (P = .027) and in patients with a complete response according to the Response Evaluation Criteria in Solid Tumors than in those who did not have a complete response (P = .014). Patients were divided into two groups according to whether they had ≥15 teeth or ≤14 teeth. There was no significant between-group difference in CRT-related adverse events. The incidence of all postoperative complications and grade II postoperative complications tended to be higher in patients with ≥15 teeth (P = .071 and P = .092, respectively), as did the 5-year overall survival rate (P = .083) and the 5-year disease-free rate (P = .007). DISCUSSION The number of healthy teeth predicted the response to preoperative CRT, postoperative complications, and the outcome of subsequent surgery in patients with rectal cancer.
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Affiliation(s)
- Toshihiro Nakao
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
| | - Mitsuo Shimada
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
| | - Kozo Yoshikawa
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
| | - Takuya Tokunaga
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
| | - Masaaki Nishi
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
| | - Hideya Kashihara
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
| | - Chie Takasu
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
| | - Yuma Wada
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
| | - Toshiaki Yoshimoto
- Department of Digestive and Transplant Surgery, Tokushima University Hospital, Tokushima, Japan
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12
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Chen Y, Zheng Y, Liu S. KRAS mutation promotes the colonization of Fusobacterium nucleatum in colorectal cancer by down-regulating SERTAD4. J Cell Mol Med 2024; 28:e70182. [PMID: 39462261 PMCID: PMC11512757 DOI: 10.1111/jcmm.70182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 10/14/2024] [Accepted: 10/19/2024] [Indexed: 10/29/2024] Open
Abstract
This study explores and verifies potential molecular targets through which KRAS mutations regulate the colonization of Fusobacterium nucleatum (FN) in colorectal cancer (CRC). This study combined multiple bioinformatics methods and biological assays. Through The Cancer Genome Atlas, Gene Expression Omnibus, Human Protein Atlas, immunohistochemistry, and co-culture assays, we further confirmed the differential expression of SERTAD4 in CRC. We delved deeper into examining how expression of SERTAD4 is linked with immune cell infiltration and the enrichment of potential pathways. Lastly, through bacterial phenotypic assays, we validated the function of SERTAD4. As a molecule associated with KRAS mutations and FN infection, the expression levels of SERTAD4 were downregulated in CRC. The diagnostic efficacy of SERTAD4 for CRC is not inferior to that of CEA. Low expression of SERTAD4 is associated with poorer overall survival in CRC. Correlation analysis found that increased expression of SERTAD4 is associated with various immune cell infiltrations and immune checkpoint genes. Finally, bacterial adhesion and invasion assays verify that SERTAD4 inhibits the adhesion and invasion abilities of FN in CRC. This study demonstrates that SERTAD4 exerts a protective role in CRC by inhibiting the colonization of FN.
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Affiliation(s)
- Yizhen Chen
- Department of Geriatric Medicine, Fujian Key Laboratory of Geriatrics Diseases, Fujian Provincial Center for Geriatrics, Fujian Provincial HospitalFuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou UniversityFuzhouFujianChina
- Shengli Clinical Medical College of Fujian Medical UniversityFuzhouFujianChina
| | - Yuanyuan Zheng
- Department of Geriatric Medicine, Fujian Key Laboratory of Geriatrics Diseases, Fujian Provincial Center for Geriatrics, Fujian Provincial HospitalFuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou UniversityFuzhouFujianChina
- Shengli Clinical Medical College of Fujian Medical UniversityFuzhouFujianChina
| | - Shaolin Liu
- Department of Geriatric Medicine, Fujian Key Laboratory of Geriatrics Diseases, Fujian Provincial Center for Geriatrics, Fujian Provincial HospitalFuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou UniversityFuzhouFujianChina
- Shengli Clinical Medical College of Fujian Medical UniversityFuzhouFujianChina
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13
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Datorre JG, Dos Reis MB, de Carvalho AC, Porto J, Rodrigues GH, Lima AB, Reis MT, Hirai W, Hashimoto CL, Guimarães DP, Reis RM. Enhancing Colorectal Cancer Screening with Droplet Digital PCR Analysis of Fusobacterium nucleatum in Fecal Immunochemical Test Samples. Cancer Prev Res (Phila) 2024; 17:471-479. [PMID: 38953141 DOI: 10.1158/1940-6207.capr-23-0331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 01/18/2024] [Accepted: 06/28/2024] [Indexed: 07/03/2024]
Abstract
Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer screening. However, specificity of FIT for colorectal cancer is not ideal and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential noninvasive biomarker for colorectal cancer and advanced adenoma detection. We aimed to evaluate the diagnostic performance of Fn detection using droplet digital PCR (ddPCR) in FIT samples from individuals enrolled in a colorectal cancer screening program with colorectal adenoma or cancer. We evaluated Fn presence in DNA isolated from FIT leftover material of 300 participants in a colorectal cancer screening program using ddPCR. The Fn DNA amount was classified as Fn-low/negative and Fn-high, and the association with patients' clinicopathological features and accuracy measurements was calculated. Fn-high levels were more prevalent in FIT-positive (47.2%, n = 34 of 72) than FIT-negative samples (28.9%, n = 66 of 228; P < 0.04). Among FIT-positive samples, high Fn levels were significantly more frequent in patients with cancer (CA, n = 8) when compared to normal (NT, n = 16; P = 0.02), non-advanced adenomas (NAA, n = 36; P = 0.01), and advanced adenomas (AA, n = 12; P = 0.01). Performance analysis of Fn in FIT-positive samples for colorectal cancer detection yielded an AUC of 0.8203 [confidence interval (CI), 0.6464-0.9942], with high sensitivity (100%) and specificity of 50%. Concluding, we showed the feasibility of detecting Fn in FIT leftovers using the ultrasensitive ddPCR technique. Furthermore, we highlighted the potential use of Fn levels in fecal samples to ameliorate colorectal cancer detection. Prevention Relevance: Fusobacterium nucleatum detection by droplet digital PCR could prioritize the selection of fecal immunochemical test-positive individuals who might benefit the most from the colonoscopy procedure.
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Affiliation(s)
- José G Datorre
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
| | - Mariana B Dos Reis
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
| | - Ana C de Carvalho
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
| | - Jun Porto
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
| | | | - Adhara B Lima
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
| | - Monise T Reis
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
- Department of Pathology, Barretos Cancer Hospital, São Paulo, Brazil
| | - Welinton Hirai
- Department of Statistics and Epidemiology, Barretos Cancer Hospital, São Paulo, Brazil
| | | | - Denise P Guimarães
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
- Department of Prevention, Barretos Cancer Hospital, São Paulo, Brazil
| | - Rui M Reis
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal
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14
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Wang X, Zhang Q, Xu R, Li X, Hong Z. Research progress on the correlation between intestinal flora and colorectal cancer. Front Oncol 2024; 14:1416806. [PMID: 39087025 PMCID: PMC11288818 DOI: 10.3389/fonc.2024.1416806] [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: 04/13/2024] [Accepted: 06/24/2024] [Indexed: 08/02/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies in the world. With the rapid pace of life and changes in diet structure, the incidence and mortality of CRC increase year by year posing a serious threat to human health. As the most complex and largest microecosystem in the human body, intestinal microecology is closely related to CRC. It is an important factor that affects and participates in the occurrence and development of CRC. Advances in next-generation sequencing technology and metagenomics have provided new insights into the ecology of gut microbes. It also helps to link intestinal flora with CRC, and the relationship between intestinal flora and CRC can be continuously understood from different levels. This paper summarizes the relationship between intestinal flora and CRC and its potential role in the diagnosis of CRC providing evidence for early screening and treatment of CRC.
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Affiliation(s)
- Xinyu Wang
- The Health Management Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Qian Zhang
- Department of Public Health, Dalian Medical University, Dalian, Liaoning, China
| | - Rongxuan Xu
- Department of Public Health, Dalian Medical University, Dalian, Liaoning, China
| | - Xiaofeng Li
- Department of Public Health, Dalian Medical University, Dalian, Liaoning, China
| | - Zhijun Hong
- The Health Management Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
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15
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Shi J, Shen H, Huang H, Zhan L, Chen W, Zhou Z, Lv Y, Xiong K, Jiang Z, Chen Q, Liu L. Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions. Front Microbiol 2024; 15:1395514. [PMID: 38962132 PMCID: PMC11220721 DOI: 10.3389/fmicb.2024.1395514] [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: 03/04/2024] [Accepted: 05/27/2024] [Indexed: 07/05/2024] Open
Abstract
The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt's functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.
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Affiliation(s)
- Jianguo Shi
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hexiao Shen
- School of Life Sciences and Health Engineering, Hubei University, Wuhan, China
| | - Hui Huang
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lifang Zhan
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wei Chen
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhuohui Zhou
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yongling Lv
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Kai Xiong
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhiwei Jiang
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qiyi Chen
- Department of Colorectal Disease, Intestinal Microenvironment Treatment Center, Tenth People’s Hospital of Tongji University, Shanghai, China
| | - Lei Liu
- Department of Gastrointestinal Surgery, Intestinal Microenvironment Treatment Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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16
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Yu LC, Li YP, Xin YM, Mao M, Pan YX, Qu YX, Luo ZD, Zhang Y, Zhang X. Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies. World J Gastrointest Oncol 2024; 16:2271-2283. [PMID: 38994170 PMCID: PMC11236247 DOI: 10.4251/wjgo.v16.i6.2271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 04/08/2024] [Accepted: 04/28/2024] [Indexed: 06/13/2024] Open
Abstract
The morbidity and mortality of gastrointestinal (GI) malignancies are among the highest in the world, posing a serious threat to human health. Because of the insidious onset of the cancer, it is difficult for patients to be diagnosed at an early stage, and it rapidly progresses to an advanced stage, resulting in poor treatment and prognosis. Fusobacterium nucleatum (F. nucleatum) is a gram-negative, spore-free anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal, esophageal, gastric, and pancreatic cancers via various intricate mechanisms. Recent development in novel research suggests that F. nucleatum may function as a biomarker in GI malignancies. Detecting the abundance of F. nucleatum in stool, saliva, and serum samples of patients may aid in the diagnosis, risk assessment, and prognosis monitoring of GI malignancies. This editorial systematically describes the biological roles and mechanisms of F. nucleatum in GI malignancies focusing on the application of F. nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F. nucleatum and GI tumors-related research.
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Affiliation(s)
- Long-Chen Yu
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Ya-Ping Li
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yue-Ming Xin
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Mai Mao
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Ya-Xin Pan
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yi-Xuan Qu
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Zheng-Dong Luo
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Xin Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
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17
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Shibata H, Yamamoto K, Hirose T, Furune S, Kakushima N, Furukawa K, Nakamura M, Honda T, Fujishiro M, Kawashima H. Characteristics of microbiomes of the saliva, duodenal bulb, and descending portion of superficial nonampullary duodenal epithelial tumors. Dig Liver Dis 2024; 56:941-950. [PMID: 38413348 DOI: 10.1016/j.dld.2024.01.212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 01/27/2024] [Accepted: 01/29/2024] [Indexed: 02/29/2024]
Abstract
INTRODUCTION Nonampullary duodenal epithelial tumors are rare, but their prevalence is increasing. Various gastrointestinal cancers have been associated with microbiomes. We evaluated the characteristics of the salivary and duodenal microbiomes of patients with nonampullary duodenal epithelial tumors. METHODS Saliva and biopsy samples from the duodenal bulb and descending portion were obtained from 15 patients with nonampullary duodenal epithelial tumors and 10 controls. Next-generation sequencing was performed to identify bacteria for comparison. RESULTS Saliva samples had higher Amplicon Sequence Variants (ASVs) and more observed species than duodenal samples. Saliva samples from patients with nonampullary duodenal epithelial tumor were dominated by Bacteroidetes and Prevotella, whereas Proteobacteria and Neisseria were dominant in the control samples. The relative abundance of bacteria was higher in patients with nonampullary duodenal epithelial tumors. Most bacteria were classified as bacteria of oral origin. Oribacterium and Stomatobaculum were significantly higher in the saliva, duodenal bulb, and descending portion of patients with nonampullary duodenal epithelial tumors. CONCLUSION Patients with nonampullary duodenal epithelial tumors had different salivary and duodenal microbiomes than controls. Bacteria types differed between groups at each site, and most bacteria of oral origin were more abundant in patients with nonampullary duodenal epithelial tumors.
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Affiliation(s)
- Hiroyuki Shibata
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Kenta Yamamoto
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takashi Hirose
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Satoshi Furune
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Naomi Kakushima
- Department of Gastroenterology, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Kazuhiro Furukawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Masanao Nakamura
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, The University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
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18
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Davoutis E, Gkiafi Z, Lykoudis PM. Bringing gut microbiota into the spotlight of clinical research and medical practice. World J Clin Cases 2024; 12:2293-2300. [PMID: 38765739 PMCID: PMC11099419 DOI: 10.12998/wjcc.v12.i14.2293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 01/30/2024] [Accepted: 04/07/2024] [Indexed: 04/29/2024] Open
Abstract
Despite the increasing scientific interest and expanding role of gut microbiota (GM) in human health, it is rarely reported in case reports and deployed in clinical practice. Proteins and metabolites produced by microbiota contribute to immune system development, energy homeostasis and digestion. Exo- and endogenous factors can alter its composition. Disturbance of microbiota, also known as dysbiosis, is associated with various pathological conditions. Specific bacterial taxa and related metabolites are involved in disease pathogenesis and therefore can serve as a diagnostic tool. GM could also be a useful prognostic factor by predicting future disease onset and preventing hospital-associated infections. Additionally, it can influence response to treatments, including those for cancers, by altering drug bioavailability. A thorough understanding of its function has permitted significant development in therapeutics, such as probiotics and fecal transplantation. Hence, GM should be considered as a ground-breaking biological parameter, and it is advisable to be investigated and reported in literature in a more consistent and systematic way.
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Affiliation(s)
- Efstathia Davoutis
- School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Zoi Gkiafi
- School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Panagis M Lykoudis
- School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
- Division of Surgery and Interventional Science, University College London, London WC1E 6BT, United Kingdom
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19
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Nie F, Zhang J, Tian H, Zhao J, Gong P, Wang H, Wang S, Yang P, Yang C. The role of CXCL2-mediated crosstalk between tumor cells and macrophages in Fusobacterium nucleatum-promoted oral squamous cell carcinoma progression. Cell Death Dis 2024; 15:277. [PMID: 38637499 PMCID: PMC11026399 DOI: 10.1038/s41419-024-06640-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 03/28/2024] [Accepted: 04/02/2024] [Indexed: 04/20/2024]
Abstract
Dysbiosis of the oral microbiota is related to chronic inflammation and carcinogenesis. Fusobacterium nucleatum (Fn), a significant component of the oral microbiota, can perturb the immune system and form an inflammatory microenvironment for promoting the occurrence and progression of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms remain elusive. Here, we investigated the impacts of Fn on OSCC cells and the crosstalk between OSCC cells and macrophages. 16 s rDNA sequencing and fluorescence in situ hybridization verified that Fn was notably enriched in clinical OSCC tissues compared to paracancerous tissues. The conditioned medium co-culture model validated that Fn and macrophages exhibited tumor-promoting properties by facilitating OSCC cell proliferation, migration, and invasion. Besides, Fn and OSCC cells can recruit macrophages and facilitate their M2 polarization. This crosstalk between OSCC cells and macrophages was further enhanced by Fn, thereby amplifying this positive feedback loop between them. The production of CXCL2 in response to Fn stimulation was a significant mediator. Suppression of CXCL2 in OSCC cells weakened Fn's promoting effects on OSCC cell proliferation, migration, macrophage recruitment, and M2 polarization. Conversely, knocking down CXCL2 in macrophages reversed the Fn-induced feedback effect of macrophages on the highly invasive phenotype of OSCC cells. Mechanistically, Fn activated the NF-κB pathway in both OSCC cells and macrophages, leading to the upregulation of CXCL2 expression. In addition, the SCC7 subcutaneous tumor-bearing model in C3H mice also substantiated Fn's ability to enhance tumor progression by facilitating cell proliferation, activating NF-κB signaling, up-regulating CXCL2 expression, and inducing M2 macrophage infiltration. However, these effects were reversed by the CXCL2-CXCR2 inhibitor SB225002. In summary, this study suggests that Fn contributes to OSCC progression by promoting tumor cell proliferation, macrophage recruitment, and M2 polarization. Simultaneously, the enhanced CXCL2-mediated crosstalk between OSCC cells and macrophages plays a vital role in the pro-cancer effect of Fn.
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Affiliation(s)
- Fujiao Nie
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Jie Zhang
- Advanced Medical Research Institute, Shandong University, Jinan, Shandong, China
| | - Haoyang Tian
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Jingjing Zhao
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Pizhang Gong
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Huiru Wang
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Suli Wang
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China
| | - Pishan Yang
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, China.
| | - Chengzhe Yang
- Department of Oral and Maxillofacial Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
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Itoh K, Matsueda S. Exploring the Potential of Humoral Immune Response to Commensal Bifidobacterium as a Biomarker for Human Health, including Both Malignant and Non-Malignant Diseases: A Perspective on Detection Strategies and Future Directions. Biomedicines 2024; 12:803. [PMID: 38672158 PMCID: PMC11048515 DOI: 10.3390/biomedicines12040803] [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: 10/24/2023] [Revised: 03/24/2024] [Accepted: 03/26/2024] [Indexed: 04/28/2024] Open
Abstract
In this comprehensive review, we explore the pivotal role of commensal Bifidobacterium (c-BIF) as potent non-self-antigens through antigenic mimicry, along with exploring the potential of humoral immune responses for both malignant and non-malignant disease. c-BIF, a predominant component of the human gut microbiome encompassing around 90% of the human genome, has emerged as a pivotal player in human biology. Over recent decades, there has been extensive research elucidating the intricate connections between c-BIF and various facets of human health, with particular emphasis on their groundbreaking impact on anti-cancer effects and the management of non-malignant diseases. The multifaceted role of c-BIF is explored, ranging from enhancing anti-tumor immunity to improving the efficacy of anti-cancer and anti-infectious disease strategies, and serving as predictive biomarkers for various diseases. Recent studies highlight not only c-BIF's promotion of anti-tumor immunity but also their role in enhancing the efficacy of immune checkpoint inhibitors. The review emphasizes the promising avenue of manipulating the gut microbiota, particularly c-BIF, for modulating cancer immunotherapy with targeted effects on tumor cells while minimizing harm to normal tissue. In the context of infectious and inflammatory diseases, the crucial role of c-BIFs in the management of COVID-19 symptoms is examined, emphasizing their impact on the severity of and immune response to COVID-19. Furthermore, c-BIF exhibits preventive and therapeutic effects on Human Papillomaviruses (HPV) and shows promise in improving inflammatory bowel diseases. The potential application of c-BIF as a biomarker for immunotherapy is explored, with a specific emphasis on its predictive and prognostic value in cancer. Suggestions are made regarding the use of humoral immune responses to cytotoxic T lymphocyte (CTL) epitope peptides that share motifs with c-BIF, proposing them as potential markers for predicting overall survival in diverse cancer patients. In conclusion, c-BIF emerges as a crucial and multifaceted determinant of human health, across anti-tumor immunity to infectious and inflammatory disease management. The manipulation of c-BIF and gut microbiota presents a promising avenue for advancing therapeutic strategies, particularly in the realm of cancer immunotherapy. Additionally, this review highlights the significance of c-BIF as potent non-self-antigens via antigenic mimicry, emphasizing the importance of robust humoral immune responses against c-BIF for preventing various diseases, including inflammatory conditions. Elevated levels of circulating antibodies against c-BIF in healthy individuals may serve as potential indicators of lower risks for malignant and non-malignant diseases.
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Affiliation(s)
| | - Satoko Matsueda
- Cancer Vaccine Center, Kurume University, Kurume 839-0863, Japan
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Miyasaka T, Yamada T, Uehara K, Sonoda H, Matsuda A, Shinji S, Ohta R, Kuriyama S, Yokoyama Y, Takahashi G, Iwai T, Takeda K, Ueda K, Kanaka S, Ohashi R, Yoshida H. Pks-positive Escherichia coli in tumor tissue and surrounding normal mucosal tissue of colorectal cancer patients. Cancer Sci 2024; 115:1184-1195. [PMID: 38297479 PMCID: PMC11007018 DOI: 10.1111/cas.16088] [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: 10/11/2023] [Revised: 01/05/2024] [Accepted: 01/12/2024] [Indexed: 02/02/2024] Open
Abstract
A significant association exists between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Escherichia coli (E. coli) containing polyketide synthetase (pks) island contribute to colorectal carcinogenesis by producing colibactin, a polyketide-peptide genotoxin. However, the functions of pks+ E. coli in initiation, proliferation, and metastasis of colorectal cancer (CRC) remain unclear. We investigated the clinical significance of pks+ E. coli to clarify its functions in CRC. This study included 413 patients with CRC. Pks+ E. coli of tumor tissue and normal mucosal tissue were quantified using droplet digital PCR. Pks+ E. coli was more abundant in Stages 0-I tumor tissue than in normal mucosal tissue or in Stages II-IV tumor tissue. High abundance of pks+ E. coli in tumor tissue was significantly associated with shallower tumor depth (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 2.3-11.3, p < 0.001) and absence of lymph node metastasis (HR = 3.0, 95% CI = 1.8-5.1, p < 0.001) in multivariable logistic analyses. Pks+ E. coli-low and -negative groups were significantly associated with shorter CRC-specific survival (HR = 6.4, 95% CI = 1.7-25.6, p = 0.005) and shorter relapse-free survival (HR = 3.1, 95% CI = 1.3-7.3, p = 0.01) compared to the pks+ E. coli-high group. Pks+ E. coli was abundant in Stages 0-I CRC and associated with CRC prognosis. These results suggest that pks+ E. coli might contribute to carcinogenesis of CRC but might not be associated with tumor progression.
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Affiliation(s)
- Toshimitsu Miyasaka
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Takeshi Yamada
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Kay Uehara
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Hiromichi Sonoda
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Akihisa Matsuda
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Seiichi Shinji
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Ryo Ohta
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Sho Kuriyama
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Yasuyuki Yokoyama
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Goro Takahashi
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Takuma Iwai
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Kohki Takeda
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Koji Ueda
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Shintaro Kanaka
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
| | - Ryuji Ohashi
- Department of Integrated Diagnostic PathologyNippon Medical SchoolTokyoJapan
| | - Hiroshi Yoshida
- Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic SurgeryNippon Medical SchoolTokyoJapan
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22
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Mori N, Nakamura A, Hirai J, Asai N, Shibata Y, Takayama M, Kawamoto Y, Miyazaki N, Sakanashi D, Ohno T, Yamada A, Suematsu H, Koita I, Chida S, Ohta T, Mikamo H. Clinical characteristics and antimicrobial susceptibility of Fusobacterium species isolated over 10 years at a Japanese university hospital. Eur J Clin Microbiol Infect Dis 2024; 43:423-433. [PMID: 38112966 DOI: 10.1007/s10096-023-04734-2] [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: 10/16/2023] [Accepted: 12/02/2023] [Indexed: 12/21/2023]
Abstract
PURPOSE Anaerobic bacteria, existing on human skin and mucous membranes, can cause severe infections with complications or mortality. We examined the clinical characteristics of patients infected with Fusobacterium spp. and assessed their antibiotic susceptibility. METHODS Clinical data were collated from patients diagnosed with Fusobacterium infections in a Japanese university hospital between 2014 and 2023. Antibiotic susceptibility tests were conducted following the Clinical and Laboratory Standards Institute guidelines. RESULTS We identified 299 Fusobacterium isolates. The median age was 61 years (range, 14-95 years), with females constituting 43.1% of the patients. Most infections were community-acquired (84.6%, 253/299). Multiple bacterial strains were isolated simultaneously in 74.6% of cases. One-fourth of the patients had solid organ malignancies (25.4%, 76/299), and 14.5% (11/76) of those had colorectal cancer. The 30-day mortality rate was 1.3%. Fusobacterium species were isolated from blood cultures in 6% (18/299) of the patients. Patients, aged 75 years or older, with cerebrovascular disease or hematologic malignancy exhibited significantly higher prevalence of blood culture isolates in univariate analysis. Each Fusobacterium species had its characteristic infection site. Approximately 5% F. nucleatum and F. necrophorum isolates showed penicillin G resistance. Moxifloxacin resistance was observed in varying degrees across strains, ranging from 4.6 to 100% of isolates. All isolates were sensitive to β-lactam/β-lactamase inhibitors, carbapenems, and metronidazole. CONCLUSION We show a link between Fusobacterium species and solid organ malignancies. We observed resistance to penicillin, cefmetazole, clindamycin, and moxifloxacin, warranting caution in their clinical use. This study offers valuable insights for managing Fusobacterium infections and guiding empirical treatments.
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Affiliation(s)
- Nobuaki Mori
- Department of Clinical Infectious Diseases, Aichi Medical University, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Akiko Nakamura
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Jun Hirai
- Department of Clinical Infectious Diseases, Aichi Medical University, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Nobuhiro Asai
- Department of Clinical Infectious Diseases, Aichi Medical University, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Yuichi Shibata
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Mina Takayama
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Yuzuka Kawamoto
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Narimi Miyazaki
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Daisuke Sakanashi
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Tomoko Ohno
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Atsuko Yamada
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Hiroyuki Suematsu
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Isao Koita
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Sumie Chida
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Toshiaki Ohta
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan
| | - Hiroshige Mikamo
- Department of Clinical Infectious Diseases, Aichi Medical University, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan.
- Department of Infection Prevention and Control, Aichi Medical University Hospital, 1-1 Yazakokarimata Nagakute-Shi, Aichi, 480-1195, Japan.
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23
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Gu Z, Liu Y. A bibliometric and visualized in oral microbiota and cancer research from 2013 to 2022. Discov Oncol 2024; 15:24. [PMID: 38302656 PMCID: PMC10834930 DOI: 10.1007/s12672-024-00878-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 01/30/2024] [Indexed: 02/03/2024] Open
Abstract
Numerous studies have highlighted the implication of oral microbiota in various cancers. However, no bibliometric analysis has been conducted on the relationship between oral microbiota and cancer. This bibliometric analysis aimed to identify the research hotspots in oral microbiota and cancer research, as well as predict future research trends. The literature published relating to oral microbiota and cancer was searched from the Web of Science Core Collection database (WoSCC) from 2013 to 2022. VOSviewer or Citespace software was used to perform the bibliometric analysis, focusing on countries, institutions, authors, journals, keywords and references. A total of 1516 publications were included in the analysis. The number of publications related oral microbiota and cancer increased annually, reaching its peak in 2022 with 287 papers. The United States (456) and China (370) were the countries with the most publications and made significant contributions to the field. Sears CL and Zhou XD were the most productive authors. The high frequency of keywords revealed key topics, including cancer (colorectal cancer, oral cancer), oral microbiota (Fusobacterium nucleatum, Porphyromonas gingivalis), and inflammation (periodontal disease). The latest trend keywords were F. nucleatum, dysbiosis, prognosis, tumor microenvironment, gastric microbiota, complications and survival, suggesting a new hotspot in the field of oral microbiota and cancer. Our study provides a comprehensive analysis of oral microbiota and cancer research, revealing an increase in publications in recent years. Future research directions will continue to focus on the diversity of oral microbiota impacted by cancers and the underlying mechanism connecting them, providing new ideas for targeted therapy of tumorigenesis.
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Affiliation(s)
- Zhiyu Gu
- Hospital of Stomatology, Zunyi Medical University, Zunyi, 563000, China
| | - Yunkun Liu
- Hospital of Stomatology, Zunyi Medical University, Zunyi, 563000, China.
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Duggan WP, Kisakol B, Woods I, Azimi M, Dussmann H, Fay J, O’Grady T, Maguire B, Reynolds IS, Salvucci M, Slade DJ, McNamara DA, Burke JP, Prehn JH. Spatial transcriptomic analysis reveals local effects of intratumoral fusobacterial infection on DNA damage and immune signaling in rectal cancer. Gut Microbes 2024; 16:2350149. [PMID: 38709233 PMCID: PMC11086019 DOI: 10.1080/19490976.2024.2350149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 04/26/2024] [Indexed: 05/07/2024] Open
Abstract
Mucinous colorectal cancer (CRC) is a common histological subtype of colorectal adenocarcinoma, associated with a poor response to chemoradiotherapy. The commensal facultative anaerobes fusobacteria, have been associated with poor prognosis specifically in mesenchymal CRC. Interestingly, fusobacterial infection is especially prevalent in mucinous CRC. The objective of this study was therefore to increase our understanding of beneficial and detrimental effects of fusobacterial infection, by contrasting host cell signaling and immune responses in areas of high vs. low infection, using mucinous rectal cancer as a clinically relevant example. We employed spatial transcriptomic profiling of 106 regions of interest from 8 mucinous rectal cancer samples to study gene expression in the epithelial and immune segments across regions of high versus low fusobacterial infection. Fusobacteria high regions were associated with increased oxidative stress, DNA damage, and P53 signaling. Meanwhile regions of low fusobacterial prevalence were characterized by elevated JAK-STAT, Il-17, Il-1, chemokine and TNF signaling. Immune masks within fusobacterial high regions were characterized by elevated proportions of cytotoxic (CD8+) T cells (p = 0.037), natural killer (NK) cells (p < 0.001), B-cells (p < 0.001), and gamma delta T cells (p = 0.003). Meanwhile, fusobacteria low regions were associated with significantly greater M2 macrophage (p < 0.001), fibroblast (p < 0.001), pericyte (p = 0.002), and endothelial (p < 0.001) counts.
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Affiliation(s)
- William P. Duggan
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
- RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Batuhan Kisakol
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
- RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Ina Woods
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Mohammedreza Azimi
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
- RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Heiko Dussmann
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
- RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Joanna Fay
- Department of Pathology, Beaumont Hospital, Dublin 9, Ireland
| | - Tony O’Grady
- Department of Pathology, Beaumont Hospital, Dublin 9, Ireland
| | - Barry Maguire
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
- RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Ian S. Reynolds
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
- RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Manuela Salvucci
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
- RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Daniel J. Slade
- Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | | | - John P. Burke
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
| | - Jochen H.M. Prehn
- Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
- RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
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25
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Yu S, Wang S, Xiong B, Peng C. Gut microbiota: key facilitator in metastasis of colorectal cancer. Front Oncol 2023; 13:1270991. [PMID: 38023192 PMCID: PMC10643165 DOI: 10.3389/fonc.2023.1270991] [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: 08/08/2023] [Accepted: 10/09/2023] [Indexed: 12/01/2023] Open
Abstract
Colorectal cancer (CRC) ranks third in terms of incidence among all kinds of cancer. The main cause of death is metastasis. Recent studies have shown that the gut microbiota could facilitate cancer metastasis by promoting cancer cells proliferation, invasion, dissemination, and survival. Multiple mechanisms have been implicated, such as RNA-mediated targeting effects, activation of tumor signaling cascades, secretion of microbiota-derived functional substances, regulation of mRNA methylation, facilitated immune evasion, increased intravasation of cancer cells, and remodeling of tumor microenvironment (TME). The understanding of CRC metastasis was further deepened by the mechanisms mentioned above. In this review, the mechanisms by which the gut microbiota participates in the process of CRC metastasis were reviewed as followed based on recent studies.
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Affiliation(s)
- Siyi Yu
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China
- Hubei Cancer Clinical Study Center, Wuhan, China
| | - Shuyi Wang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China
- Hubei Cancer Clinical Study Center, Wuhan, China
| | - Bin Xiong
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China
- Hubei Cancer Clinical Study Center, Wuhan, China
| | - Chunwei Peng
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China
- Hubei Cancer Clinical Study Center, Wuhan, China
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26
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Ou S, Chen H, Wang H, Ye J, Liu H, Tao Y, Ran S, Mu X, Liu F, Zhu S, Luo K, Guan Z, Jin Y, Huang R, Song Y, Liu SL. Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis. J Transl Med 2023; 21:704. [PMID: 37814323 PMCID: PMC10561506 DOI: 10.1186/s12967-023-04527-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Accepted: 09/15/2023] [Indexed: 10/11/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. METHODS Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. RESULTS F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. CONCLUSIONS Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.
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Affiliation(s)
- Suwen Ou
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Haipeng Chen
- Department of Colorectal Surgery, National Clinical Research Center of Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Hufei Wang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Jinhua Ye
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Huidi Liu
- Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province), College of Pharmacy, Harbin Medical University, Harbin, 150081, China
- Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University-University of Calgary, Harbin Medical University, Harbin, 150081, China
| | - Yangbao Tao
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Songlin Ran
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Xiaoqin Mu
- Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province), College of Pharmacy, Harbin Medical University, Harbin, 150081, China
- Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University-University of Calgary, Harbin Medical University, Harbin, 150081, China
| | - Fangzhou Liu
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Shuang Zhu
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Kangjia Luo
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315020, China
| | - Zilong Guan
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
- Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
| | - Yinghu Jin
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
| | - Rui Huang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
| | - Yanni Song
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
| | - Shu-Lin Liu
- Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province), College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
- Cumming School of Medicine Centre for Infection and Genomics, Harbin Medical University-University of Calgary, Harbin Medical University, Harbin, 150081, China.
- Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, T2N 4N1, Canada.
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27
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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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28
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Nasiri K, Amiri Moghaddam M, Etajuri EA, Badkoobeh A, Tavakol O, Rafinejad M, Forutan Mirhosseini A, Fathi A. Periodontitis and progression of gastrointestinal cancer: current knowledge and future perspective. Clin Transl Oncol 2023; 25:2801-2811. [PMID: 37036595 DOI: 10.1007/s12094-023-03162-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 02/26/2023] [Indexed: 04/11/2023]
Abstract
Periodontitis is a polymicrobial disorder caused by dysbiosis. Porphyromonas gingivalis (P.gingivalis) and Fusobacterium nucleatum (F.nucleatum) are pathobiont related to periodontitis pathogenesis and were found to be abundant in the intestinal mucosa of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. Besides, periodontal infections have been found in a variety of tissues and organs, indicating that periodontitis is not just an inflammation limited to the oral cavity. Considering the possible translocation of pathobiont from the oral cavity to the gastrointestinal (GI) tract, this study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the relationship between periodontitis and GI malignancies by focusing on the oral/gut axis.
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Affiliation(s)
- Kamyar Nasiri
- Department of Dentistry, Islamic Azad University, Tehran, Iran
| | - Masoud Amiri Moghaddam
- Department of Periodontics, Dental Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Enas Abdalla Etajuri
- Department of Restorative Dentistry, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
| | - Ashkan Badkoobeh
- Department of Oral and Maxillofacial Surgery, School of Dentistry, Qom University of Medical Sciences, Qom, Iran
| | - Omid Tavakol
- Department of Prosthodontics, Islamic Azad University, Shiraz, Iran
| | | | | | - Amirhossein Fathi
- Department of Prosthodontics, Dental Materials Research Center, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.
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Takeda K, Koi M, Okita Y, Sajibu S, Keku TO, Carethers JM. Fusobacterium nucleatum Load Correlates with KRAS Mutation and Sessile Serrated Pathogenesis in Colorectal Adenocarcinoma. CANCER RESEARCH COMMUNICATIONS 2023; 3:1940-1951. [PMID: 37772997 PMCID: PMC10530411 DOI: 10.1158/2767-9764.crc-23-0179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 07/14/2023] [Accepted: 09/05/2023] [Indexed: 09/30/2023]
Abstract
Fusobacterium nucleatum (Fn) has been frequently detected in colorectal cancer. A high load of Fn has been associated with subtypes of colorectal cancers, located in the proximal colon, exhibiting microsatellite instability-high (MSI-H), MLH1 promoter hypermethylation, the CpG island hypermethylation phenotype-high, or BRAF mutation in some studies. Although these features characterize the sessile serrated pathway (SSP) of colon cancers, other studies have shown that Fn infection is associated with KRAS mutations mainly characteristic of non-serrated neoplasia. It is also not clear at what point the association of Fn infection with these genomic alterations is established during colorectal carcinogenesis. Here we show that MSI-H, MLH1 hypermethylation, BRAF mutation or KRAS mutations were independently associated with Fn infection in colorectal cancer. On the other hand, increasing Fn copy number in tissues was associated with increased probability to exhibit MSI-H, MLH1 hypermethylation or BRAF mutations but not KRAS mutations in colorectal cancer. We also show that Fn load was significantly less than that of colorectal cancer and no association was detected between BRAF/KRAS mutations or MLH1 hypermethylation and Fn infection in adenomas. Our combined data suggest that increasing loads of Fn during and/or after adenomacarcinoma transition might promote SSP but not KRAS-driven colorectal carcinogenesis. Alternatively, Fn preferentially colonizes colorectal cancers with SSP and KRAS mutations but can expand more in colorectal cancers with SSP. SIGNIFICANCE The authors demonstrated that Fn is enriched in colorectal cancers exhibiting the SSP phenotype, and in colorectal cancers carrying KRAS mutations. Fn infection should be considered as a candidate risk factor specific to colorectal cancers with the SSP phenotype and with KRAS mutations.
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Affiliation(s)
- Koki Takeda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine and Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan
| | - Minoru Koi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine and Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan
- Divsion of Gastroenterology and Hepatology, Department of Medicine and Moores Cancer Center, University of California San Diego, San Diego, California
| | - Yoshiki Okita
- Department of Gastrointestinal and Pediatric Surgery, Graduate School of Medicine, Mie University, Mie, Japan
| | - Sija Sajibu
- Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
| | - Temitope O. Keku
- Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - John M. Carethers
- Division of Gastroenterology and Hepatology, Department of Internal Medicine and Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan
- Divsion of Gastroenterology and Hepatology, Department of Medicine and Moores Cancer Center, University of California San Diego, San Diego, California
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Li X, Feng J, Wang Z, Liu G, Wang F. Features of combined gut bacteria and fungi from a Chinese cohort of colorectal cancer, colorectal adenoma, and post-operative patients. Front Microbiol 2023; 14:1236583. [PMID: 37614602 PMCID: PMC10443710 DOI: 10.3389/fmicb.2023.1236583] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 07/20/2023] [Indexed: 08/25/2023] Open
Abstract
Colorectal cancer (CRC) accounts for the third highest morbidity burden among malignant tumors worldwide. Previous studies investigated gut microbiome changes that occur during colorectal adenomas (CRA) progression to overt CRC, thus highlighting the importance of the gut microbiome in carcinogenesis. However, few studies have examined gut microbiome characteristics across the entire spectrum, from CRC development to treatment. The study used 16S ribosomal ribonucleic acid and internal transcribed spacer amplicon sequencing to compare the composition of gut bacteria and fungi in a Chinese cohort of healthy controls (HC), CRC patients, CRA patients, and CRC postoperative patients (PP). Our analysis showed that beta diversity was significantly different among the four groups based on the gut bacterial and fungal data. A total of 51 species of bacteria and 8 species of fungi were identified in the HC, CRA, CRC, and PP groups. Correlation networks for both the gut bacteria and fungi in HC vs. CRA, HC vs. CRC, and HC vs. PP indicated some hub bacterial and fungal genera in each model, and the correlation between bacterial and fungal data indicated that a highly significant negative correlation exists among groups. Quantitative polymerase chain reaction (qPCR) analysis in a large cohort of HC, CRC, CRA, and PP patients demonstrated a significantly increasing trend of Fusobacterium nucleatum, Bifidobacterium bifidum, Candida albicans, and Saccharomyces cerevisiae in the feces of CRC patients than that of HC patients (p < 0.01). However, the abundance levels of CRA and PP were significantly lower in HC patients than those in CRC patients. Further studies are required to identify the functional consequences of the altered bacterial/fungal composition on metabolism and CRC tumorigenesis in the host.
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Affiliation(s)
- Xiaopeng Li
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Radiation Oncology, Anhui No. 2 Provincial People's Hospital, Hefei, China
| | - Jiahui Feng
- School of Life Sciences, Anhui Medical University, Hefei, China
| | - Zhanggui Wang
- Department of Radiation Oncology, Anhui No. 2 Provincial People's Hospital, Hefei, China
| | - Gang Liu
- School of Life Sciences, Anhui Medical University, Hefei, China
| | - Fan Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Duggan WP, Salvucci M, Kisakol B, Lindner AU, Reynolds IS, Dussmann H, Fay J, O'Grady T, Longley DB, Ginty F, Mc Donough E, Slade DJ, Burke JP, Prehn JHM. Increased Fusobacterium tumoural abundance affects immunogenicity in mucinous colorectal cancer and may be associated with improved clinical outcome. J Mol Med (Berl) 2023; 101:829-841. [PMID: 37171483 PMCID: PMC10300184 DOI: 10.1007/s00109-023-02324-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 04/04/2023] [Accepted: 04/19/2023] [Indexed: 05/13/2023]
Abstract
There is currently an urgent need to identify factors predictive of immunogenicity in colorectal cancer (CRC). Mucinous CRC is a distinct histological subtype of CRC, associated with a poor response to chemotherapy. Recent evidence suggests the commensal facultative anaerobe Fusobacterium may be especially prevalent in mucinous CRC. The objectives of this study were to assess the association of Fusobacterium abundance with immune cell composition and prognosis in mucinous CRC. Our study included two independent colorectal cancer patient cohorts, The Cancer Genome Atlas (TCGA) cohort, and a cohort of rectal cancers from the Beaumont RCSI Cancer Centre (BRCC). Multiplexed immunofluorescence staining of a tumour microarray (TMA) from the BRCC cohort was undertaken using Cell DIVE technology. Our cohorts included 87 cases (13.3%) of mucinous and 565 cases (86.7%) of non-mucinous CRC. Mucinous CRC in the TCGA dataset was associated with an increased proportion of CD8 + lymphocytes (p = 0.018), regulatory T-cells (p = 0.001) and M2 macrophages (p = 0.001). In the BRCC cohort, mucinous RC was associated with enhanced CD8 + lymphocyte (p = 0.022), regulatory T-cell (p = 0.047), and B-cell (p = 0.025) counts. High Fusobacterium abundance was associated with an increased proportion of CD4 + lymphocytes (p = 0.031) and M1 macrophages (p = 0.006), whilst M2 macrophages (p = 0.043) were under-represented in this cohort. Patients with increased Fusobacterium relative abundance in our mucinous CRC TCGA cohort tended to have better clinical outcomes (DSS: likelihood ratio p = 0.04, logrank p = 0.052). Fusobacterium abundance may be associated with improved outcomes in mucinous CRC, possibly due to a modulatory effect on the host immune response. KEY MESSAGES: • Increased Fusobacterium relative abundance was not found to be associated with microsatellite instability in mucinous CRC. • Increased Fusobacterium relative abundance was associated with an M2/M1 macrophage switch, which is especially significant in mucinous CRC, where M2 macrophages are overexpressed. • Increased Fusobacterium relative abundance was associated with a significant improvement in disease specific survival in mucinous CRC. • Our findings were validated at a protein level within our own in house mucinous and non-mucinous rectal cancer cohorts.
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Affiliation(s)
- William P Duggan
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
- Department of Physiology and Medical Physicsand, RCSI Centre for Systems Medicine , Royal College of Surgeons in Ireland, Dublin 2, Ireland
| | - Manuela Salvucci
- Department of Physiology and Medical Physicsand, RCSI Centre for Systems Medicine , Royal College of Surgeons in Ireland, Dublin 2, Ireland
- Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland
| | - Batuhan Kisakol
- Department of Physiology and Medical Physicsand, RCSI Centre for Systems Medicine , Royal College of Surgeons in Ireland, Dublin 2, Ireland
- Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland
| | - Andreas U Lindner
- Department of Physiology and Medical Physicsand, RCSI Centre for Systems Medicine , Royal College of Surgeons in Ireland, Dublin 2, Ireland
- Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland
| | - Ian S Reynolds
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
- Department of Physiology and Medical Physicsand, RCSI Centre for Systems Medicine , Royal College of Surgeons in Ireland, Dublin 2, Ireland
| | - Heiko Dussmann
- Department of Physiology and Medical Physicsand, RCSI Centre for Systems Medicine , Royal College of Surgeons in Ireland, Dublin 2, Ireland
- Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland
| | - Joanna Fay
- RCSI Biobank, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Tony O'Grady
- RCSI Biobank, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Daniel B Longley
- Centre for Cancer Research & Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, UK
| | | | | | - Daniel J Slade
- Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - John P Burke
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
| | - Jochen H M Prehn
- Department of Physiology and Medical Physicsand, RCSI Centre for Systems Medicine , Royal College of Surgeons in Ireland, Dublin 2, Ireland.
- Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
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Ağagündüz D, Cocozza E, Cemali Ö, Bayazıt AD, Nanì MF, Cerqua I, Morgillo F, Saygılı SK, Berni Canani R, Amero P, Capasso R. Understanding the role of the gut microbiome in gastrointestinal cancer: A review. Front Pharmacol 2023; 14:1130562. [PMID: 36762108 PMCID: PMC9903080 DOI: 10.3389/fphar.2023.1130562] [Citation(s) in RCA: 95] [Impact Index Per Article: 47.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 01/10/2023] [Indexed: 01/26/2023] Open
Abstract
Gastrointestinal cancer represents one of the most diagnosed types of cancer. Cancer is a genetic and multifactorial disease, influenced by the host and environmental factors. It has been stated that 20% of cancer is caused by microorganisms such as Helicobacter pylori, hepatitis B and C virus, and human papillomavirus. In addition to these well-known microorganisms associated with cancer, it has been shown differences in the composition of the microbiota between healthy individuals and cancer patients. Some studies have suggested the existence of the selected microorganisms and their metabolites that can promote or inhibit tumorigenesis via some mechanisms. Recent findings have shown that gut microbiome and their metabolites can act as cancer promotors or inhibitors. It has been shown that gastrointestinal cancer can be caused by a dysregulation of the expression of non-coding RNA (ncRNA) through the gut microbiome. This review will summarize the latest reports regarding the relationship among gut microbiome, ncRNAs, and gastrointestinal cancer. The potential applications of diagnosing and cancer treatments will be discussed.
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Affiliation(s)
- Duygu Ağagündüz
- Department of Nutrition and Dietetics, Gazi University, Emek, Ankara, Turkey
| | | | - Özge Cemali
- Department of Nutrition and Dietetics, Gazi University, Emek, Ankara, Turkey
| | - Ayşe Derya Bayazıt
- Department of Nutrition and Dietetics, Gazi University, Emek, Ankara, Turkey
| | | | - Ida Cerqua
- Department of Pharmacy, University of Naples “Federico II”, Naples, Italy
| | - Floriana Morgillo
- Medical Oncology, Department of Precision Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, Naples, Italy
| | - Suna Karadeniz Saygılı
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States,Department of Histology and Embryology, Kütahya Health Sciences University, Kütahya, Turkey
| | - Roberto Berni Canani
- Department of Translational Medical Science and ImmunoNutritionLab at CEINGE Biotechnologies Research Center and Task Force for Microbiome Studies, University of Naples Federico II, Naples, Italy
| | - Paola Amero
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States,*Correspondence: Raffaele Capasso, ; Paola Amero,
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy,*Correspondence: Raffaele Capasso, ; Paola Amero,
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Wu W, Ouyang Y, Zheng P, Xu X, He C, Xie C, Hong J, Lu N, Zhu Y, Li N. Research trends on the relationship between gut microbiota and colorectal cancer: A bibliometric analysis. Front Cell Infect Microbiol 2023; 12:1027448. [PMID: 36699721 PMCID: PMC9868464 DOI: 10.3389/fcimb.2022.1027448] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 12/19/2022] [Indexed: 01/10/2023] Open
Abstract
Background Colorectal cancer (CRC)is the third most common cancer in the world and the second leading cause of cancer-related deaths, and over the past two decades, many of these researchers have provided a substantial amount of important information on the role of gut microbes in the development and progression of CRC. A causal relationship between the presence of specific microorganisms and CRC development has also been validated. Although a large number of papers related to this area have been published, no bibliometric study has been conducted to review the current state of research in this area and to highlight the research trends and hotspots in this area. This study aims to analyze the current status and future research trends of gut microbiota and CRC through bibliometric analysis. Methods Publications from 2001 to 2022 were retrieved from the Web of Science Core Collection database and screened according to inclusion criteria. VOSviewer and CiteSpace software were used to visualize the research trends in this field, including the analysis of title, country, institution, author, number of publications, year of publication, number of citations, journal, and H-index. Results A total of 863 studies were eventually identified, and the articles retrieved were cited an average of 44.85 times each. The number of publications on this topic has been increased steadily since 2011. China and the USA have made the largest contribution in the field. FRONTIERS IN MICROBIOLOGY is the top productive journal with 26 papers, and Gut journal has the highest average citation (167.23). Shanghai Jiao Tong University is the most contributive institution. Professor Yu J, Sung, Joseph J. Y and Fang JY are the most productive authors in this field. Keyword co-occurrence analysis showed that the terms of "Gut Microbiota", "Colorectal Cancer", "Inflammation", "Probiotic" and "Fusobacterium Nucleatum" were the most frequent, which revealed the research hotpots and trends in this field. Conclusions There has been a growing number of publications over the past two decades according to the global trends. China and the USA still maintained the leading position in this field. However, collaboration between institutions needs to be strengthened. It's commended to pay attention to the latest hotspots, such as "F. nucleatum" and "probiotics". This bibliometric analysis evaluates the scope and trends of gut microbiota and CRC, providing a useful perspective on current research and future directions for studying the link between the gut microbiota and CRC.
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Affiliation(s)
- Weigen Wu
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yaobin Ouyang
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Pan Zheng
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xinbo Xu
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Cong He
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Chuan Xie
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Junbo Hong
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Nonghua Lu
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yin Zhu
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Nianshuang Li
- Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Fan Z, Tang P, Li C, Yang Q, Xu Y, Su C, Li L. Fusobacterium nucleatum and its associated systemic diseases: epidemiologic studies and possible mechanisms. J Oral Microbiol 2023; 15:2145729. [PMID: 36407281 PMCID: PMC9673791 DOI: 10.1080/20002297.2022.2145729] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background Fusobacterium nucleatum (F. nucleatum) is an anaerobic oral commensal and the major coaggregation bridge organism linking early and late colonisers. In recent years, a large number of studies suggest that F. nucleatum is closely related to the development of various systemic diseases, such as cardiovascular diseases, adverse pregnancy outcomes, inflammatory bowel diseases, cancer, Alzheimer's disease, respiratory infection, rheumatoid arthritis, etc. Objective To review the effect of F. nucleatum on systemic diseases and its possible pathogenesis and to open new avenues for prevention and treatment of F. nucleatum-associated systemic diseases. Design The research included every article published up to July 2022 featuring the keywords 'Systemic diseases' OR 'Atherosclerotic cardiovascular diseases' OR 'Atherosclerosis' OR 'Adverse pregnancy outcomes' OR 'Inflammatory bowel disease' OR 'Ulcerative colitis' OR 'Crohn’s disease' OR 'Cancers' OR 'Oral squamous cell carcinomas' OR 'Gastrointestinal cancers' OR 'Colorectal cancer' OR 'Breast cancer' OR 'Genitourinary cancers' OR 'Alzheimer’s disease ' OR 'Rheumatoid arthritis' OR 'Respiratory diseases' AND 'Fusobacterium nucleatum' OR 'Periodontal pathogen' OR 'Oral microbiota' OR 'Porphyromonas gingivalis' and was conducted in the major medical databases. Results F. nucleatum can induce immune response and inflammation in the body through direct or indirect pathways, and thus affect the occurrence and development of systemic diseases. Only by continuing to investigate the pathogenic lifestyles of F. nucleatum will we discover the divergent pathways that may be leveraged for diagnostic, preventive and therapeutic purposes.
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Affiliation(s)
- Zixin Fan
- Department of Periodontics, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Shanghai road 1, Nanjing, Jiangsu, China
- Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Pengzhou Tang
- Department of Periodontics, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Shanghai road 1, Nanjing, Jiangsu, China
- Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Cheng Li
- Department of Periodontics, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Shanghai road 1, Nanjing, Jiangsu, China
- Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Qi Yang
- Department of Periodontics, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Shanghai road 1, Nanjing, Jiangsu, China
- Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yan Xu
- Department of Periodontics, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Shanghai road 1, Nanjing, Jiangsu, China
- Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chuan Su
- State KeyLaboratory of Reproductive Medicine, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology and Immunology, Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lu Li
- Department of Periodontics, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
- Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, Shanghai road 1, Nanjing, Jiangsu, China
- Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
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Löwenmark T, Löfgren-Burström A, Zingmark C, Ljuslinder I, Dahlberg M, Edin S, Palmqvist R. Tumour Colonisation of Parvimonas micra Is Associated with Decreased Survival in Colorectal Cancer Patients. Cancers (Basel) 2022; 14:5937. [PMID: 36497419 PMCID: PMC9736682 DOI: 10.3390/cancers14235937] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/24/2022] [Accepted: 11/28/2022] [Indexed: 12/04/2022] Open
Abstract
Increasing evidence suggests that the gut microbiota may impact colorectal cancer (CRC) development and progression. In this study, the tumour colonisation of two CRC-associated bacteria, Parvimonas micra and Fusobacterium nucleatum, was studied in relation to patient survival in a cohort of 257 CRC patients. Colonisation of P. micra and F. nucleatum was analysed in fresh frozen tumour tissue (n = 112) and in faeces (n = 250) by qPCR. When analysing tumour tissues, both P. micra and F. nucleatum were found to be associated with decreased five-year cancer-specific survival, an association that remained significant in multivariable analysis for P. micra. Furthermore, we found significant associations of high levels of P. micra and F. nucleatum with tumour molecular characteristics, i.e., tumours mutated in BRAFV600E, and tumours of the MSI subtype. The analysis of faecal samples showed weaker associations with prognosis and tumour molecular characteristics. In conclusion, our findings support a novel association of tumour colonisation of P. micra with decreased patient survival. A better understanding of the role of the gut microbiota in CRC might contribute to the advancement of prognostic tools and new targets for therapy.
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Affiliation(s)
- Thyra Löwenmark
- Department of Medical Biosciences, Pathology, Umeå University, SE-90185 Umeå, Sweden
| | - Anna Löfgren-Burström
- Department of Medical Biosciences, Pathology, Umeå University, SE-90185 Umeå, Sweden
| | - Carl Zingmark
- Department of Medical Biosciences, Pathology, Umeå University, SE-90185 Umeå, Sweden
| | - Ingrid Ljuslinder
- Department of Radiation Sciences, Oncology, Umeå University, SE-90185 Umeå, Sweden
| | - Michael Dahlberg
- Department of Surgical and Perioperative Sciences, Surgery, Umeå University, SE-90185 Umeå, Sweden
| | - Sofia Edin
- Department of Medical Biosciences, Pathology, Umeå University, SE-90185 Umeå, Sweden
| | - Richard Palmqvist
- Department of Medical Biosciences, Pathology, Umeå University, SE-90185 Umeå, Sweden
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Ou S, Wang H, Tao Y, Luo K, Ye J, Ran S, Guan Z, Wang Y, Hu H, Huang R. Fusobacterium nucleatum and colorectal cancer: From phenomenon to mechanism. Front Cell Infect Microbiol 2022; 12:1020583. [PMID: 36523635 PMCID: PMC9745098 DOI: 10.3389/fcimb.2022.1020583] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 11/09/2022] [Indexed: 11/30/2022] Open
Abstract
Colorectal cancer(CRC) is the third most frequent malignant tumor. The gut microbiome acts as a vital component of CRC etiology. Fusobacterium nucleatum(Fn) is a key member of colorectal cancer-associated bacteria. But we lack a systematic and in-depth understanding on its role in CRC evolution. In this article, We reviewed the abundance changes and distribution of Fn in CRC occurrence and development, potential effect of Fn in the initiation of CRC, the source of intratumoral Fn and the cause of its tropism to CRC. In addition, We described the mechanism by which Fn promotes the malignant biological behavior of CRC, affects CRC response to therapy, and shapes the tumor immune microenvironment in great detail. Based on the relationship between Fn and CRC, we proposed strategies for CRC prevention and treatment, and discussed the feasibility and limitations of specific cases, to gain insights into further basic and clinical research in the future.
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Affiliation(s)
- Suwen Ou
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Hufei Wang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yangbao Tao
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Kangjia Luo
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China,Department of Gastrointestinal Surgery, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China
| | - Jinhua Ye
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Songlin Ran
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Zilong Guan
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China,Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yuliuming Wang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Hanqing Hu
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Rui Huang
- Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China,*Correspondence: Rui Huang,
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Wang Y, Wen Y, Wang J, Lai X, Xu Y, Zhang X, Zhu X, Ruan C, Huang Y. Clinicopathological differences of high Fusobacterium nucleatum levels in colorectal cancer: A review and meta-analysis. Front Microbiol 2022; 13:945463. [PMID: 36406461 PMCID: PMC9672069 DOI: 10.3389/fmicb.2022.945463] [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: 05/17/2022] [Accepted: 09/01/2022] [Indexed: 11/06/2022] Open
Abstract
Objective To systematically evaluate the significance of Fusobacterium nucleatum (Fn) levels the clinicopathological impacts of cancer. Methods Literature from Pubmed, Embase, and Web of Science was retrieved to collect all English literatures on the correlation between Fn and cancer, and the quality of literatures collected was assessed based on the Newcastle-Ottawa Quality Assessment Scale. The heterogeneity and sensitivity were detected by Stata 14.0 software, and the correlation between Fn and cancer clinicopathological as the effect variables was assessed according to the odds ratio (OR) and 95% confidence interval (CI). The forest plot was drawn. Results A total of 19 articles meeting the inclusion criteria were selected. The incidence of Fn prevalence varied considerably (range: 6.1 to 83.3%) and was greater than 10% in 13 of 19 studies. Compared with those with no/low Fn levels, the high levels of Fn was positively associated with vascular invasion, nerve invasion, depth of invasion, and distant metastasis [vascular invasion: OR = 1.66, 95%CI(1.07, 2.57), I2 = 21.9%, fixed effect model; nerve invasion: OR = 1.36, 95%CI(1.00, 1.84), I2 = 43.1%, fixed effect model; infiltration depth: OR = 1.94, 95%CI(1.20, 3.15), I2 = 67.2%, random effect model; distant metastasis: OR = 1.80, 95%CI(1.23, 2.64), I2 = 3.4%, fixed effect model]. Patients with MLH1 methylation always present a higher Fn levels than those without methylation [OR = 2.53, 95%CI(1.42, 4.53), P = 0.01, I2 = 57.5%, random effect model]. Further, Fn was associatedwith the molecular characteristics of cancers [MSI-H Vs. MSS/MSI-low: OR = 2.92, 95%CI(1.61, 5.32), P = 0.01, I2 = 63.2%, random effect model; High Vs. Low/Negative CIMP: OR = 2.23, 95%CI(1.64, 3.03), P = 0.01, I2 = 64.2%, random effect model; KRAS mutation Vs. wild-type: OR = 1.24, 95%CI(1.04, 1.48), P = 0.02, I2 = 27.0%, fixed effect model; Present Vs. Abscent BRAF mutations: OR = 1.88, 95%CI(1.44, 2.45), P = 0.01, I2 = 24.2%, fixed effect model]. The cancer patients with high levels of Fn often have worse RFS than those with no/low Fn levels[OR = 1.14, 95%CI(0.61, 1.68), P = 0.01, I2 = 80.7%, random effect model]. Conclusion This review and meta-analysis showed that Fn could be used to predict unfavorable prognosis and function as potential prognostic biomarkers in colorectal cancer (CRC). Our data may have implications for targeting Fn to develop strategies for cancer prevention and treatment.
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Affiliation(s)
- Yi Wang
- School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Department of Pathology, Xi’an Ninth Hospital Affiliated to Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yuting Wen
- School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
- Department of Pathology, Xi’an Ninth Hospital Affiliated to Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Jiayin Wang
- School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
- *Correspondence: Jiayin Wang,
| | - Xin Lai
- School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Ying Xu
- School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xuanping Zhang
- School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xiaoyan Zhu
- School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Chenglin Ruan
- School of Computer Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yao Huang
- Department of Pathology, Xi’an Ninth Hospital Affiliated to Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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Baik JE, Li L, Shah MA, Freedberg DE, Jin Z, Wang TC, Han YW. Circulating IgA Antibodies Against Fusobacterium nucleatum Amyloid Adhesin FadA are a Potential Biomarker for Colorectal Neoplasia. CANCER RESEARCH COMMUNICATIONS 2022; 2:1497-1503. [PMID: 36970057 PMCID: PMC10035380 DOI: 10.1158/2767-9764.crc-22-0248] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 09/14/2022] [Accepted: 10/03/2022] [Indexed: 11/06/2022]
Abstract
Fusobacterium nucleatum (Fn) is a gram-negative oral anaerobe and prevalent in colorectal cancer. Fn encodes a unique amyloid-like adhesin, FadA complex (FadAc), consisting of intact pre-FadA and cleaved mature FadA, to promote colorectal cancer tumorigenesis. We aimed to evaluate circulating anti-FadAc antibody levels as a biomarker for colorectal cancer. Circulating anti-FadAc IgA and IgG levels were measured by ELISA in two study populations. In study 1, plasma samples from patients with colorectal cancer (n = 25) and matched healthy controls (n = 25) were obtained from University Hospitals Cleveland Medical Center. Plasma levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (mean ± SD: 1.48 ± 1.07 μg/mL) compared with matched healthy controls (0.71 ± 0.36 μg/mL; P = 0.001). The increase was significant in both early (stages I and II) and advanced (stages III and IV) colorectal cancer. In study 2, sera from patients with colorectal cancer (n = 50) and patients with advanced colorectal adenomas (n = 50) were obtained from the Weill Cornell Medical Center biobank. Anti-FadAc antibody titers were stratified according to the tumor stage and location. Similar as study 1, serum levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (2.06 ± 1.47 μg/mL) compared with patients with colorectal adenomas (1.49 ± 0.99 μg/mL; P = 0.025). Significant increase was limited to proximal cancers, but not distal tumors. Anti-FadAc IgG was not increased in either study population, suggesting that Fn likely translocates through the gastrointestinal tract and interact with colonic mucosa. Anti-FadAc IgA, but not IgG, is a potential biomarker for early detection of colorectal neoplasia, especially for proximal tumors. Significance Fn, an oral anaerobe highly prevalent in colorectal cancer, secretes the amyloid-like FadAc to promote colorectal cancer tumorigenesis. We report that circulating levels of anti-FadAc IgA, but not IgG, are increased in patients with both early and advanced colorectal cancer compared with the healthy controls, and especially in those with proximal colorectal cancer. Anti-FadAc IgA may be developed into a serological biomarker for early detection of colorectal cancer.
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Affiliation(s)
- Jung Eun Baik
- Division of Periodontics, College of Dental Medicine, Columbia University Irving Medical Center, New York, New York
| | - Li Li
- Department of Family Medicine and UVA Comprehensive Cancer Center, University of Virginia, Charlottesville, Virginia
| | - Manish A. Shah
- Division of Gastroenterology and Hepatology, Weill Cornell School of Medicine, New York, New York
| | - Daniel E. Freedberg
- Division of Digestive and Liver Diseases, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York
| | - Zhezhen Jin
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York
| | - Timothy C. Wang
- Division of Digestive and Liver Diseases, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York
| | - Yiping W. Han
- Division of Periodontics, College of Dental Medicine, Columbia University Irving Medical Center, New York, New York
- Division of Digestive and Liver Diseases, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York
- Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York
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Kashyap S, Pal S, Chandan G, Saini V, Chakrabarti S, Saini NK, Mittal A, Thakur VK, Saini AK, Saini RV. Understanding the cross-talk between human microbiota and gastrointestinal cancer for developing potential diagnostic and prognostic biomarkers. Semin Cancer Biol 2022; 86:643-651. [PMID: 33971261 DOI: 10.1016/j.semcancer.2021.04.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 04/19/2021] [Accepted: 04/29/2021] [Indexed: 02/07/2023]
Abstract
The interaction between gut microbes and gastrointestinal (GI) tract carcinogenesis has always attracted researchers' attention to identify therapeutic targets or potential prognostic biomarkers. Various studies have suggested that the microbiota do show inflammation and immune dysregulation, which led to carcinogenesis in GI tract. In this review, we have focused on the role of microbes present in the gut, intestine, or faeces in GI tract cancers, including esophageal cancer, gastric cancer, and colorectal cancer. Herein, we have discussed the importance of the microbes and their metabolites, which could serve as diagnostic biomarkers for cancer detection, especially in the early stage, and prognostic markers. To maximize the effect of the treatment strategies, an accurate evaluation of the prognosis is imperative for clinicians. There is a vast difference in the microbiota profiles within a population and across the populations depending upon age, diet, lifestyle, genetic makeup, use of antibiotics, and environmental factors. Therefore, the diagnostic efficiency of the microbial markers needs to be further validated. A deeper understanding of the GI cancer and the host microbiota is needed to acquire pivotal information about disease status.
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Affiliation(s)
- Sheetal Kashyap
- Department of Biotechnology, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133207, Haryana, India
| | - Soumya Pal
- Department of Biotechnology, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133207, Haryana, India
| | - Gourav Chandan
- Central Research Cell, MM Institute of Medical Sciences & Research, Maharishi Markandeshwar (Deemed to be University), Mullana, 133207, Haryana, India
| | - Vipin Saini
- Maharishi Markandeshwar University, Solan, 173229, Himachal Pradesh, India
| | - Sasanka Chakrabarti
- Central Research Cell, MM Institute of Medical Sciences & Research, Maharishi Markandeshwar (Deemed to be University), Mullana, 133207, Haryana, India
| | - Neeraj K Saini
- Department of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Amit Mittal
- Central Research Cell, MM Institute of Medical Sciences & Research, Maharishi Markandeshwar (Deemed to be University), Mullana, 133207, Haryana, India
| | - Vijay Kumar Thakur
- Biorefining and Advanced Materials Research Center, Scotland's Rural College (SRUC), Kings Buildings, Edinburgh, EH9 3JG, UK
| | - Adesh K Saini
- Department of Biotechnology, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133207, Haryana, India.
| | - Reena V Saini
- Department of Biotechnology, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133207, Haryana, India.
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Xie Y, Jiao X, Zeng M, Fan Z, Li X, Yuan Y, Zhang Q, Xia Y. Clinical Significance of Fusobacterium nucleatum and Microsatellite Instability in Evaluating Colorectal Cancer Prognosis. Cancer Manag Res 2022; 14:3021-3036. [PMID: 36262751 PMCID: PMC9576466 DOI: 10.2147/cmar.s382464] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 10/04/2022] [Indexed: 02/05/2023] Open
Abstract
Objective Both genetic and microbial factors play important roles in colorectal cancer (CRC) development. The effects of Fusobacterium nucleatum (F. nucleatum) and microsatellite instability (MSI) on CRC prognosis require more clinical evidence. We aimed to investigate the role of F. nucleatum and MSI as biomarkers in predicting the prognosis of CRC. Methods CRC patients in various TNM stages were enrolled. MSI status and F. nucleatum were detected by immunohistochemical staining of formalin-fixed paraffin-embedded (FFPE) specimens. The associations between MSI status and F. nucleatum and clinical parameters were analyzed. Results MSI tumors were more frequently observed in the colon than in the rectum. Cancerous tissues had higher levels of F. nucleatum than adjacent noncancerous tissues. There were no significant differences in F. nucleatum abundance in different age, sex, tumor stage, location, and tumor marker groups. MSI status was associated with tumor location and stage. Survival analyses revealed that disease-free survival (DFS) was significantly longer in the F. nucleatum-negative, younger age, and TNM stage I-II groups (p< 0.05), and age, advanced TNM stage (III and IV), and F. nucleatum status were independent factors for poor prognosis. Multivariate Cox regression and receiver operating characteristic (ROC) curve analyses showed that conventional tumor biomarkers of CRC had more prognostic value than F. nucleatum and MSI. Conclusion Age, advanced TNM stage, and F. nucleatum positivity were independent factors of poor prognosis, suggesting that F. nucleatum and MSI may contribute to the identification of new strategies for the prevention and treatment of CRC.
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Affiliation(s)
- Yanxuan Xie
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China
| | - Xiaoyang Jiao
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China
| | - Mi Zeng
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China
| | - Zhiqiang Fan
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China
| | - Xin Li
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China
| | - Yumeng Yuan
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China
| | - Qiaoxin Zhang
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China
| | - Yong Xia
- The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, People’s Republic of China
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Kapsetaki SE, Marquez Alcaraz G, Maley CC, Whisner CM, Aktipis A. Diet, Microbes, and Cancer Across the Tree of Life: a Systematic Review. Curr Nutr Rep 2022; 11:508-525. [PMID: 35704266 PMCID: PMC9197725 DOI: 10.1007/s13668-022-00420-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2022] [Indexed: 11/09/2022]
Abstract
PURPOSE OF REVIEW Cancers are a leading cause of death in humans and for many other species. Diet has often been associated with cancers, and the microbiome is an essential mediator between diet and cancers. Here, we review the work on cancer and the microbiome across species to search for broad patterns of susceptibility associated with different microbial species. RECENT FINDINGS Some microbes, such as Helicobacter bacteria, papillomaviruses, and the carnivore-associated Fusobacteria, consistently induce tumorigenesis in humans and other species. Other microbes, such as the milk-associated Lactobacillus, consistently inhibit tumorigenesis in humans and other species. We systematically reviewed over a thousand published articles and identified links between diet, microbes, and cancers in several species of mammals, birds, and flies. Future work should examine a larger variety of host species to discover new model organisms for human preclinical trials, to better understand the observed variance in cancer prevalence across species, and to discover which microbes and diets are associated with cancers across species. Ultimately, this could help identify microbial and dietary interventions to diagnose, prevent, and treat cancers in humans as well as other animals.
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Affiliation(s)
- Stefania E Kapsetaki
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA.
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA.
| | - Gissel Marquez Alcaraz
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA
| | - Carlo C Maley
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Biodesign Center for Biocomputing, Security and Society, Arizona State University, Tempe, USA
| | - Corrie M Whisner
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
- Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, USA
| | - Athena Aktipis
- Arizona Cancer Evolution Center, Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Department of Psychology, Arizona State University, Tempe, AZ, USA
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Ono T, Yamaguchi T, Takao M, Kojika E, Iijima T, Horiguchi SI. Fusobacterium nucleatum load in MSI colorectal cancer subtypes. Int J Clin Oncol 2022; 27:1580-1588. [PMID: 35859218 DOI: 10.1007/s10147-022-02218-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 07/04/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND Fusobacterium nucleatum (F. nucleatum) infection may lead to colorectal cancer (CRC) development in the context of microsatellite instability (MSI). To date, however, the relationship between F. nucleatum load and MSI CRC subtypes has not been clarified. METHODS One hundred seventy-nine consecutive patients with CRC were enrolled in the present study. In 94 patients with MSI CRC, 32 had hereditary MSI CRC from Lynch syndrome, 62 had sporadic MSI CRC, while the remaining 85 had microsatellite stable (MSS) CRC. The association of the F. nucleatum load with each CRC subtype and the patients' clinicopathological characteristics was examined. RESULTS Of the 179 patients with CRC, 158 (88.3%) were F. nucleatum-positive. A high F. nucleatum load was found in 84.4% (27/32), 96.8% (60/62), and 83.5% (71/85) of the patients with hereditary MSI CRC, sporadic MSI CRC, and MSS CRC, respectively (P = 0.024). In terms of clinicopathological features, a high F. nucleatum load was significantly associated with female, right-sided CRC, BRAF V600E, CpG island methylator phenotype-positive CRC, and MSI CRC (P = 0.008, P = 0.015, P = 0.007, P = 0.006, and P < 0.001, respectively). However, the clinicopathological characteristics did not differ significantly by F. nucleatum load between hereditary and sporadic MSI CRCs without tumor depth. CONCLUSIONS The F. nucleatum load was higher in hereditary MSI CRC than in MSS CRC as well as sporadic MSI CRC. These findings may contribute to preventing CRC in hereditary MSI CRC through appropriate intervention.
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Affiliation(s)
- Tomoyuki Ono
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Tatsuro Yamaguchi
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. .,Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. .,Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
| | - Misato Takao
- Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Ekumi Kojika
- Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.,Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Takeru Iijima
- Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.,Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Shin-Ichiro Horiguchi
- Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
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Yamaoka Y, Sasai M, Suehiro Y, Hashimoto S, Goto A, Yamamoto N, Suzuki N, Higaki S, Fujii I, Suzuki C, Matsumoto T, Hoshida T, Koga M, Tsutsumi T, Lim LA, Matsubara Y, Tomochika S, Yoshida S, Hazama S, Yotsuyanagi H, Nagano H, Sakaida I, Takami T, Yamasaki T. Comparison of two primer-probe sets of Fusobacterium nucleatum using droplet digital polymerase chain reaction for the detection of colorectal neoplasia from faecal samples. Ann Clin Biochem 2022; 59:396-403. [PMID: 35821582 DOI: 10.1177/00045632221115559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Although faecal DNA testing of Fusobacterium nucleatum (Fn) is expected to be useful for colorectal neoplasia detection, there is no standardized quantification method of Fn. We performed this study to establish a possible standardized method. METHODS In this study, 322 participants including 71 subjects without colorectal neoplasia (control group), 31 patients with non-advanced colorectal adenoma, 93 patients with advanced colorectal adenoma, and 127 patients with colorectal cancer were enrolled. Faecal Fn were quantified by droplet digital PCR (ddPCR) using two PCR primer-probe sets reported previously that are tentatively named Fn1 and Fn2. Fn1 has been used in ddPCR by us and Fn2 has been widely used in quantitative real-time PCR. RESULTS The Fn copy number using Fn1 was five times higher than that using Fn2, with a linear relationship shown between them. Receiver operating characteristic curve analysis showed the area under the curve (AUC) to be almost the same between Fn1 and Fn2 in discriminating between the control group and the colorectal cancer group (AUC = 0.81 and 0.81, respectively), and between the control/non-advanced colorectal adenoma group and the advanced colorectal adenoma/colorectal cancer group (AUC = 0.74 and 0.74, respectively). CONCLUSIONS As the diagnostic performance was quite similar between Fn1 and Fn2, ddPCR-based Fn testing using Fn1 and Fn2 could be a possible standardized method for a colorectal neoplasia screening test, considering that Fn levels quantified by Fn1 are about five times higher than those by Fn2.
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Affiliation(s)
- Yuko Yamaoka
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Mai Sasai
- Division of Laboratory, Yamaguchi University Hospital, Ube, Japan.,Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yutaka Suehiro
- Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shinichi Hashimoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Atsushi Goto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Naoki Yamamoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Nobuaki Suzuki
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shingo Higaki
- Department of Gastroenterology, St. Hill Hospital, Ube, Japan
| | | | | | - Toshihiko Matsumoto
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.,Division of Laboratory, Yamaguchi University Hospital, Ube, Japan
| | - Tomomi Hoshida
- Division of Laboratory, Yamaguchi University Hospital, Ube, Japan
| | - Michiko Koga
- Division of Infectious Diseases, The Advanced Clinical Research Centre, The Institute of Medical Science, 26430The University of Tokyo, Tokyo, Japan
| | - Takeya Tsutsumi
- Division of Infectious Diseases, The Advanced Clinical Research Centre, The Institute of Medical Science, 26430The University of Tokyo, Tokyo, Japan
| | - Lay A Lim
- Department of General Medicine, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Yasuo Matsubara
- Department of General Medicine, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Shinobu Tomochika
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shin Yoshida
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shoichi Hazama
- Department of Translational Research and Developmental Therapeutics Against Cancer, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, The Advanced Clinical Research Centre, The Institute of Medical Science, 26430The University of Tokyo, Tokyo, Japan
| | - Hiroaki Nagano
- Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Isao Sakaida
- Department of Gastroenterology, St. Hill Hospital, Ube, Japan
| | - Taro Takami
- Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Takahiro Yamasaki
- Division of Laboratory, Yamaguchi University Hospital, Ube, Japan.,Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan
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Li M, Shao D, Zhou J, Gu J, Qin J, Li X, Hao C, Wei W. Microbial Diversity and Composition in Six Different Gastrointestinal Sites among Participants Undergoing Upper Gastrointestinal Endoscopy in Henan, China. Microbiol Spectr 2022; 10:e0064521. [PMID: 35467373 PMCID: PMC9241895 DOI: 10.1128/spectrum.00645-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 03/29/2022] [Indexed: 11/21/2022] Open
Abstract
The objective of this study was to describe and compare the dynamic microbiota characteristics in the gastrointestinal (GI) tract in Chinese participants via high-throughput sequencing techniques. The study collected saliva, esophageal swab, cardia biopsy, noncardia biopsy, gastric juice, and fecal specimens from 40 participants who underwent upper GI tract cancer screening in Linzhou (Henan, China) in August 2019. The V4 region of 16S rRNA genes was amplified and sequenced using the Illumina MiniSeq platform. The observed amplicon sequence variants (ASVs) gradually decreased from saliva to esophageal swab, cardia biopsy, noncardia biopsy, and gastric juice specimens and then increased from gastric juice to fecal specimens (P < 0.05). Each GI site had its own microbial characteristics that overlapped those of adjacent sites. Characteristic genera for each site were as follows: Neisseria and Prevotella in saliva, Streptococcus and Haemophilus in the esophagus, Helicobacter in the noncardia, Pseudomonas in gastric juice, Faecalibacterium, Roseburia, and Blautia in feces, and Weissella in the cardia. Helicobacter pylori-positive participants had decreased observed ASVs (cardia, P < 0.01; noncardia, P < 0.001) and Shannon index values (cardia, P < 0.001; noncardia, P < 0.001) compared with H. pylori-negative participants both in cardia and noncardia specimens. H. pylori infection played a more important role in the microbial composition of noncardia than of cardia specimens. In gastric juice, the gastric pH and H. pylori infection had similar additive effects on the microbial diversity and composition. These results show that each GI site has its own microbial characteristics that overlap those of adjacent sites and that differences and commonalities between and within microbial compositions coexist, providing essential foundations for the continuing exploration of disease-associated microbiota. IMPORTANCE Upper gastrointestinal (UGI) tract cancer is one of the most common cancers worldwide, while limited attention has been paid to the UGI microbiota. Microbial biomarkers, such as Fusobacteria nucleatum and Helicobacter pylori, bring new ideas for early detection of UGI tract cancer, which may be a highly feasible method to reduce its disease burden. This study revealed that each gastrointestinal site had its own microbial characteristics that overlapped those of adjacent sites. There were significant differences between the microbial compositions of the UGI sites and feces. Helicobacter pylori played a more significant role in the microbial composition of the noncardia stomach than in that of the cardia. Gastric pH and Helicobacter pylori had similar additive effects on the microbial diversity of gastric juice. These findings played a key role in delineating the microbiology spectrum of the gastrointestinal tract and provided baseline information for future microbial exploration covering etiology, primary screening, treatment, outcome, and health care products.
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Affiliation(s)
- Minjuan Li
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dantong Shao
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiachen Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, China
| | - Jianhua Gu
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | | | - Xinqing Li
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Changqing Hao
- Department of Endoscopy, Cancer Institute/Hospital of Linzhou, Linzhou, China
| | - Wenqiang Wei
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Li L, Zhao C, Kong F, Li YC, Wang C, Chen S, Tan HY, Liu Y, Wang D. Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function. Front Pharmacol 2022; 13:898906. [PMID: 35662701 PMCID: PMC9160181 DOI: 10.3389/fphar.2022.898906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 04/19/2022] [Indexed: 12/12/2022] Open
Abstract
Calf thymus polypeptide (CTP), with a molecular mass of <10 kDa, is prepared from the thymus of less than 30-day-old newborn cattle. In the present study, the inhibitory function of CTP in colorectal cancer (CRC) was investigated in B6/JGpt-Apcem1Cin(MinC)/Gpt (ApcMin/+) mice. CTP hampered tumor development and enhanced the ratio of CD3e−NK1.1+ cells by 113.0% and CD3e+CD28+ cells by 84.7% in the peripheral blood of ApcMin/+ mice. CTP improved the richness, diversity, and evenness of the intestinal microbiota of ApcMin/+ mice, particularly by regulating the abundance of immune-related microorganisms. CTP effectively regulated the expression of immune-related cytokines, such as interleukin (IL)-2 (15.19% increment), IL-12 (17.47% increment), and transforming growth factor (TGF)-β (11.19% reduction). Additionally, it enhanced the levels of CD4 and CD8, as well as the ratio of helper T lymphocytes (Th)1/Th2 in the spleen and tumors of ApcMin/+ mice. In CTP-treated mice, reduced levels of programmed death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), activated nuclear factor of activated T cells 1 (NFAT1), and nuclear factor κB (NF-κB) p65 signaling were noted. Collectively, the anti-CRC effect of CTP is related to the modulation of intestinal microbiota-mediated immune function, which provides a reference for CTP as a therapeutic drug or a combination drug used in CRC treatment in a clinical setting.
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Affiliation(s)
- Lanzhou Li
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, China.,School of Life Sciences, Jilin University, Changchun, China
| | - Chenfei Zhao
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, China
| | - Fange Kong
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, China
| | - Yi-Cong Li
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, China
| | - Chunxia Wang
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, China
| | - Shanshan Chen
- School of Life Sciences, Jilin University, Changchun, China
| | - Hor-Yue Tan
- Centre for Chinese Herbal Medicine Drug Development, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Yang Liu
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, China
| | - Di Wang
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, China.,School of Life Sciences, Jilin University, Changchun, China
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Fusobacterium Nucleatum Is a Risk Factor for Metastatic Colorectal Cancer. Curr Med Sci 2022; 42:538-547. [DOI: 10.1007/s11596-022-2597-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 12/29/2021] [Indexed: 12/24/2022]
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Huang C, Sun Y, Liao SR, Chen ZX, Lin HF, Shen WZ. Suppression of Berberine and Probiotics ( in vitro and in vivo) on the Growth of Colon Cancer With Modulation of Gut Microbiota and Butyrate Production. Front Microbiol 2022; 13:869931. [PMID: 35572672 PMCID: PMC9096942 DOI: 10.3389/fmicb.2022.869931] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 03/29/2022] [Indexed: 12/24/2022] Open
Abstract
Background and Objective An increasing number of evidence has revealed that the gut microbiome functions in immunity, inflammation, metabolism, and homeostasis and is considered to be crucial due to its balance between human health and diseases such as cancer, leading to the emergence of treatments that target intestinal microbiota. Probiotics are one of them. However, many challenges remain regarding the effects of probiotics in cancer treatment. Berberine (BBR), a natural extract of Rhizoma Coptidis and extensively used in the treatment of gastrointestinal diseases, has been found to have antitumor effects in vivo and in vitro by many recent studies, but its definite mechanisms are still unclear. This study aimed to explore the inhibitory effect of BBR and probiotics on the growth of colon cancer cells in vitro and in vivo, and the regulatory influence on the gut microbiome and butyrate production. Methods Colon cancer cell line HT29 was used to establish a xenograft model of nude mice and an in vitro model. A total of 44 nude mice and HT29 cells were divided into control, model, model + BBR, model + probiotics, and model + combination of BBR with probiotics (CBPs). Live combined Bifidobacterium, Lactobacillus, and Enterococcus powder (LCBLEP) was used as a probiotic preparation. LCBLEP was cultured in the liquid medium under anaerobic conditions (the number of viable bacteria should reach 1 × 108CFU), and the supernatant was collected, and it is called probiotic supernatant (PS). Model + BBR and model + probiotics groups were treated with BBR and LCBLEP or PS for 4 weeks in vivo or 48, 72, and 96 h in vitro, respectively. Tumor volume or cell proliferation was measured. Gut microbiota was pyrosequenced using a 16S rDNA amplicon. HDAC1 mRNA level in HT29 cells and sodium butyrate (SB) expression in the serum of mice was detected by QPCR and ELISA. Results The treatment of BBR and CBP reduced the growth of neoplasms in mice to a different extent (p > 0.05), especially at 14 days. The inhibitory effect of LCBLEP on tumor growth was more significant, especially at 11-21 days (p < 0.05). Inhibition of BBR on in vitro proliferation was concentration-dependent. The suppression of 75% probiotic supernatant (PS) on the proliferation was the most significant. The supplement of LCBLEP significantly increased the richness and evenness of the gut microbe. BBR dramatically increased the abundance of Bacteroidetes and Proteobacteria, with reduced Ruminococcus, followed by the LCBLEP. The LCBLEP reduced the relative abundance of Verrucomicrobia and Akkermansia, and the CBP also promoted the relative level of Bacteroidetes but reduced the level of Verrucomicrobia and Akkermansia. BBR and LCBLEP or CBP improved the alpha and beta diversity and significantly affected the biomarker and metabolic function of the gut microbe in nude mice with colon cancer. The level of HDAC1 mRNA was reduced in HT29 cells treated with BBR or PS (p < 0.05), the mice treated with BBR revealed a significantly increased concentration of SB in serum (p < 0.05), and the inhibitory effect of SB on the proliferation of HT29 cells was stronger than panobinostat and TSA. Conclusion Although the combination of BBR and probiotics has no advantage in inhibiting tumor growth compared with the drug alone, BBR can be used as a regulator of the intestinal microbiome similar to the probiotics by mediating the production of SB during reducing the growth of colon cancer.
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Affiliation(s)
- Chao Huang
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shenzhen University, People's Hospital of Shenzhen Baoan District, Shenzhen, China
| | - Ying Sun
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shenzhen University, People's Hospital of Shenzhen Baoan District, Shenzhen, China
| | - Sheng-Rong Liao
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shenzhen University, People's Hospital of Shenzhen Baoan District, Shenzhen, China
| | - Zhao-Xin Chen
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shenzhen University, People's Hospital of Shenzhen Baoan District, Shenzhen, China
| | - Han-Feng Lin
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shenzhen University, People's Hospital of Shenzhen Baoan District, Shenzhen, China
| | - Wei-Zeng Shen
- Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shenzhen University, People's Hospital of Shenzhen Baoan District, Shenzhen, China
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Kim Y, Cho NY, Kang GH. Prognostic and clinicopathological significance of Fusobacterium nucleatum in colorectal cancer: a systemic review and meta-analysis. J Pathol Transl Med 2022; 56:144-151. [PMID: 35581731 PMCID: PMC9119808 DOI: 10.4132/jptm.2022.03.13] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 03/13/2022] [Indexed: 11/23/2022] Open
Abstract
Background Fusobacterium nucleatum has been identified to promote tumor progression in colorectal cancer (CRC). However, association between F. nucleatum and prognostic or clinicopathological features has been diverse among studies, which could be affected by type of biospecimen (formalin-fixed paraffin-embedded or fresh frozen [FF]). Methods Articles were systemically reviewed for studies that included the correlation between F. nucleatum and prognosis or clinicopathological features in CRC. Results Ten articles, eight studies with survival-related features involving 3,199 patients and nine studies with clinical features involving 2,655 patients, were eligible for the meta-analysis. Overall survival, disease-free survival, and cancer-specific survival were all associated with worse prognosis in F. nucleatum–high patients (p<.05). In subgroup analysis, only studies with FF tissues retained prognostic significance with F. nucleatum. In meta-analysis of clinicopathological variables, F. nucleatum level was associated with location within colon, pT category, MLH1 hypermethylation, microsatellite instability status, and BRAF mutation regardless of type of biospecimen. However, lymph node metastasis and KRAS mutation was only associated with F. nucleatum level in FF-based studies. Conclusions In conclusion, type of biospecimen could affect the role of F. nucleatum as a biomarker associated with clinicopathological features and prognosis.
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Affiliation(s)
- Younghoon Kim
- Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Nam Yun Cho
- Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Gyeong Hoon Kang
- Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
- Corresponding Author: Gyeong Hoon Kang, MD, PhD, Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-22-740-8272, Fax: +82-2-765-5600, E-mail:
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Huo RX, Wang YJ, Hou SB, Wang W, Zhang CZ, Wan XH. Gut mucosal microbiota profiles linked to colorectal cancer recurrence. World J Gastroenterol 2022; 28:1946-1964. [PMID: 35664963 PMCID: PMC9150055 DOI: 10.3748/wjg.v28.i18.1946] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 02/01/2022] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Emerging evidence links gut microbiota to various human diseases including colorectal cancer (CRC) initiation and development. However, gut microbiota profiles associated with CRC recurrence and patient prognosis are not completely understood yet, especially in a Chinese cohort. AIM To investigate the relationship between gut mucosal microbiota profiles and CRC recurrence and patient prognosis. METHODS We obtained the composition and structure of gut microbiota collected from 75 patients diagnosed with CRC and 26 healthy controls. The patients were followed up by regular examination to determine whether tumors recurred. Triplet-paired samples from on-tumor, adjacent-tumor and off-tumor sites of patients diagnosed with/without CRC recurrence were analyzed to assess spatial-specific patterns of gut mucosal microbiota by 16S ribosomal RNA sequencing. Next, we carried out bioinformatic analyses, Kaplan-Meier survival analyses and Cox regression analyses to determine the relationship between gut mucosal microbiota profiles and CRC recurrence and patient prognosis. RESULTS We observed spatial-specific patterns of gut mucosal microbiota profiles linked to CRC recurrence and patient prognosis. A total of 17 bacterial genera/families were identified as potential biomarkers for CRC recurrence and patient prognosis, including Anaerotruncus, Bacteroidales, Coriobacteriaceae, Dialister, Eubacterium, Fusobacterium, Filifactor, Gemella, Haemophilus, Mogibacteriazeae, Pyramidobacter, Parvimonas, Porphyromonadaceae, Slackia, Schwartzia, TG5 and Treponema. CONCLUSION Our work suggests that intestinal microbiota can serve as biomarkers to predict the risk of CRC recurrence and patient death.
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Affiliation(s)
- Rui-Xue Huo
- Department of Oncology, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China
| | - Yi-Jia Wang
- Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China
| | - Shao-Bin Hou
- Advanced Studies in Genomics, Proteomics and Bioinformatics, University of Hawaii at Manoa, Honolulu, HI 96822, United States
| | - Wei Wang
- TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China
| | - Chun-Ze Zhang
- Department of Colorectal Surgery, Tianjin Union Medical Center, Nankai University, Tianjin 300121, China
- Tianjin Institute of Coloproctology, Tianjin 300121, China
| | - Xue-Hua Wan
- TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China
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Zhang X, Zhang Y, Gui X, Zhang Y, Zhang Z, Chen W, Zhang X, Wang Y, Zhang M, Shang Z, Xin Y, Zhang Y. Salivary Fusobacterium nucleatum serves as a potential biomarker for colorectal cancer. iScience 2022; 25:104203. [PMID: 35479401 PMCID: PMC9035728 DOI: 10.1016/j.isci.2022.104203] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 02/14/2022] [Accepted: 04/01/2022] [Indexed: 12/24/2022] Open
Abstract
Fusobacterium nucleatum (Fn) is primarily colonized in the oral cavity. Recently, Fn has been closely associated with the tumorigenesis of colorectal cancer (CRC). Here, we showed that the relative level of Fn DNA was increased in the saliva of the CRC group compared with the normal colonoscopy, hyperplastic polyp, and adenoma groups. Receiver operating characteristic curve analysis illustrated that Fn DNA was superior to carcinoembryonic antigen and carbohydrate antigen 19-9 in CRC diagnosis. Moreover, levels of Fn DNA were associated with the overall survival and disease-free survival of CRC patients, which was an independent factor for prognostic prediction. Transcriptome sequencing identified 1,287 differentially expressed mRNAs in tumor tissues between CRC patients with high-Fn and low-Fn infection. Kyoto encyclopedia of genes and genomes analysis showed that ECM-receptor interaction and focal adhesion were the top two significant pathways. Overall, salivary Fn DNA may be a noninvasive diagnostic and prognostic biomarker for CRC patients.
Fusobacterium nucleatum DNA level is increased in saliva of colorectal cancer patients Salivary F. nucleatum DNA is a biomarker for colorectal cancer diagnosis Salivary F. nucleatum DNA is an independent prognostic factor KEGG identified relationships to ECM-receptor interaction and focal adhesion pathways
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