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Wen Y, Ullah H, Ma R, Farooqui NA, Li J, Alioui Y, Qiu J. Anemarrhena asphodeloides Bunge polysaccharides alleviate lipoteichoic acid-induced lung inflammation and modulate gut microbiota in mice. Heliyon 2024; 10:e39390. [PMID: 39469699 PMCID: PMC11513480 DOI: 10.1016/j.heliyon.2024.e39390] [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: 06/28/2024] [Revised: 10/10/2024] [Accepted: 10/14/2024] [Indexed: 10/30/2024] Open
Abstract
Pneumonia remains a prevalent infection primary ailment characterized by severe lung inflammation, leading to respiratory distress and significant mortality rates, particularly affecting young children in less developed regions. This study explores the therapeutic potential of low and high-molecular weight polysaccharides derived from Anemarrhena asphodeloides in a murine model of lipoteichoic acid (LTA)-induced pneumonia, which represents bacterial-induced lung inflammation. Administration of Anemarrhena asphodeloides polysaccharides effectively alleviated LTA-induced symptoms, including decreased lung and colon inflammation, and restored dysbiosis of gut microbiota. Polysaccharide treatment notably increased mucin-2 expression, reduced serum cytokine levels (IL-10, TNF-α), and increased tight junction protein production (ZO-1, Occludin, Claudin). Additionally, polysaccharides promoted a significant recovery in gut microbiota composition, indicating potential prebiotic effects. These findings highlight the therapeutic capability of Anemarrhena asphodeloides polysaccharides against LTA-induced pneumonia through gut microbiota modulation and restored intestinal homeostasis.
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Affiliation(s)
- Yuqi Wen
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China
| | - Hidayat Ullah
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China
| | - Renzhen Ma
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China
| | - Nabeel Ahmad Farooqui
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China
| | - Jiaxin Li
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China
| | - Yamina Alioui
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China
| | - Juanjuan Qiu
- Central Lab, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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Onyeaghala GC, Sharma S, Oyenuga M, Staley CM, Milne GL, Demmer RT, Shaukat A, Thyagarajan B, Straka RJ, Church TR, Prizment AE. The Effects of Aspirin Intervention on Inflammation-Associated Lingual Bacteria: A Pilot Study from a Randomized Clinical Trial. Microorganisms 2024; 12:1609. [PMID: 39203451 PMCID: PMC11357305 DOI: 10.3390/microorganisms12081609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/02/2024] [Accepted: 08/04/2024] [Indexed: 09/03/2024] Open
Abstract
Several bacterial taxa enriched in inflammatory bowel diseases and colorectal cancer (CRC) are found in the oral cavity. We conducted a pilot study nested within a six-week aspirin intervention in a randomized placebo-controlled trial to test their response to aspirin intervention. Fifty healthy subjects, 50-75 years old, were randomized to receive 325 mg aspirin (n = 30) or placebo (n = 20) orally once daily for six weeks. Oral tongue swabs were collected at baseline and week six. We estimated the association between aspirin use and the temporal changes in the relative abundance of pre-specified genus level taxa from pre- to post-treatment. The temporal change in relative abundance differed for eight genus level taxa between the aspirin and placebo groups. In the aspirin group, there were significant increases in the relative abundances of Neisseria, Streptococcus, Actinomyces, and Rothia and significant decreases in Prevotella, Veillonella, Fusobacterium, and Porphyromonas relative to placebo. The log ratio of Neisseria to Fusobacterium declined more in the aspirin group than placebo, signaling a potential marker associated with aspirin intervention. These preliminary findings should be validated using metagenomic sequencing and may guide future studies on the role of aspirin on taxa in various oral ecological niches.
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Affiliation(s)
- Guillaume C. Onyeaghala
- Division of Nephrology, Hennepin Healthcare, University of Minnesota, Minneapolis, MN 55415, USA;
| | - Shweta Sharma
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA; (S.S.); (B.T.)
| | - Mosunmoluwa Oyenuga
- Department of Internal Medicine, SSM Health St. Mary’s Hospital—St. Louis, St. Louis, MO 63117, USA;
| | - Christopher M. Staley
- Department of Surgery, Medical School, University of Minnesota, Minneapolis, MN 55455, USA;
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA;
| | - Ginger L. Milne
- Department of Medicine, Vanderbilt School of Medicine, Nashville, TN 37232, USA;
| | - Ryan T. Demmer
- Mayo Clinic College of Medicine & Sciences, Rochester, MN 55905, USA;
| | - Aasma Shaukat
- Department of Population Health, New York University Grossman School of Medicine, New York University, New York, NY 10016, USA;
| | - Bharat Thyagarajan
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA; (S.S.); (B.T.)
- Department of Laboratory Medicine & Pathology, Medical School, University of Minnesota, Minneapolis, MN 55455, USA
| | - Robert J. Straka
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA;
| | - Timothy R. Church
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA;
- Division of Environmental Health Sciences, School of Public Health, University of Minnesota, Saint Paul, MN 55108, USA
| | - Anna E. Prizment
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA; (S.S.); (B.T.)
- Department of Laboratory Medicine & Pathology, Medical School, University of Minnesota, Minneapolis, MN 55455, USA
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Yoo W, Shealy NG, Zieba JK, Torres TP, Baltagulov M, Thomas JD, Shelton CD, McGovern AG, Foegeding NJ, Olsan EE, Byndloss MX. Salmonella Typhimurium expansion in the inflamed murine gut is dependent on aspartate derived from ROS-mediated microbiota lysis. Cell Host Microbe 2024; 32:887-899.e6. [PMID: 38806059 PMCID: PMC11189616 DOI: 10.1016/j.chom.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 03/20/2024] [Accepted: 05/01/2024] [Indexed: 05/30/2024]
Abstract
Inflammation boosts the availability of electron acceptors in the intestinal lumen, creating a favorable niche for pathogenic Enterobacteriaceae. However, the mechanisms linking intestinal inflammation-mediated changes in luminal metabolites and pathogen expansion remain unclear. Here, we show that mucosal inflammation induced by Salmonella enterica serovar Typhimurium (S. Tm) infection increases intestinal levels of the amino acid aspartate. S. Tm used aspartate-ammonia lyase (aspA)-dependent fumarate respiration for growth in the murine gut only during inflammation. AspA-dependent growth advantage was abolished in the gut of germ-free mice and restored in gnotobiotic mice colonized with members of the classes Bacteroidia and Clostridia. Reactive oxygen species (ROS) produced during the host response caused lysis of commensal microbes, resulting in the release of microbiota-derived aspartate that was used by S. Tm, in concert with nitrate-dependent anaerobic respiration, to outcompete commensal Enterobacteriaceae. Our findings demonstrate the role of microbiota-derived amino acids in driving respiration-dependent S. Tm expansion during colitis.
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Affiliation(s)
- Woongjae Yoo
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea
| | - Nicolas G Shealy
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Jacob K Zieba
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Teresa P Torres
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Madi Baltagulov
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Julia D Thomas
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Catherine D Shelton
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Anna G McGovern
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Nora J Foegeding
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Erin E Olsan
- Department of Biological Sciences, California State University, Sacramento, CA 95819, USA
| | - Mariana X Byndloss
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Microbiome Innovation Center, Vanderbilt University, Nashville, TN 37235, USA; Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
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Cariño AMD, Balanag GA, Magat EM, Fellizar A, Ortin TS, Villaflores O, Guevarra L, Albano PM. Antibody response to enterotoxigenic Bacteroides fragilis of Filipino colorectal cancer patients. ASIAN BIOMED 2023; 17:273-280. [PMID: 38161350 PMCID: PMC10754502 DOI: 10.2478/abm-2023-0070] [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] [Indexed: 01/03/2024]
Abstract
Background Several species of the gut microbiota have been implicated in colorectal cancer (CRC) development. The anaerobic bacterium enterotoxigenic Bacteroides fragilis (ETBF), has been identified to produce fragilysin, a toxin known to cleave E-cadherin, thereby leading to carcinogenesis. Objective To determine the antibody response of CRC patients against ETBF to ascertain whether significant difference exists or whether antibody response is related to tumor grade and tumor stage. Methods Informed consent was obtained from histologically confirmed CRC casesand their age- and sex-matched clinically healthy controls. Plasma samples from the participants were subjected to in-house enzyme-linked immunosorbent assay (ELISA) to determine their antibody levels. Results Using ETBF total protein as coating antigen, 38/39 (97%) CRC cases and 36/39 (92%) controls showed anti-ETBF IgG above cut-off, while all (100%) CRC cases and 36/39 (92%) controls had anti-ETBF IgA levels above cut-off. With culture broth as coating antigen, all (100%) CRC cases and 37/39 (95%) controls had anti-ETBF IgG levels above cut-off. For anti-ETBF IgA, all (100%) cases and controls had levels above cut-off. Statistical analysis reveals no significant difference (P > 0.05) on the number of CRC cases and controls with IgG and IgA antibody levels above cut-off value. Also, there's no significant difference (P > 0.05) in the mean anti-ETBF antibody levels of cases who were at different tumor grade (well differentiated and moderately and poorly differentiated) and tumor stage (early and advanced). Conclusions These results suggest that Filipino CRC cases and their clinically healthy matched controls exhibit antibody responses against ETBF.
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Affiliation(s)
- Ana Maria D. Cariño
- Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Manila1015, Philippines
- The Graduate School, University of Santo Tomas, España Manila1015, Philippines
- College of Teacher Education, Quirino State University, Quirino3401, Philippines
| | - Gregg Austine Balanag
- Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Manila1015, Philippines
- The Graduate School, University of Santo Tomas, España Manila1015, Philippines
| | - Edrienne Myenna Magat
- Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Manila1015, Philippines
- The Graduate School, University of Santo Tomas, España Manila1015, Philippines
| | - Allan Fellizar
- Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Manila1015, Philippines
- The Graduate School, University of Santo Tomas, España Manila1015, Philippines
- Hematology Division, Mariano Marcos Memorial Hospital and Medical Center, Batac, Ilocos Norte2906, Philippines
| | - Teresa Sy Ortin
- The Graduate School, University of Santo Tomas, España Manila1015, Philippines
- Benavides Cancer Institute, University of Santo Tomas Hospital, España Manila1015, Philippines
| | - Oliver Villaflores
- Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Manila1015, Philippines
- The Graduate School, University of Santo Tomas, España Manila1015, Philippines
- Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, España Manila1015, Philippines
| | - Leonardo Guevarra
- Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Manila1015, Philippines
- Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, España Manila1015, Philippines
| | - Pia Marie Albano
- Research Center for the Natural and Applied Sciences, University of Santo Tomas, España Manila1015, Philippines
- The Graduate School, University of Santo Tomas, España Manila1015, Philippines
- Department of Biological Sciences, College of Science, University of Santo Tomas, España Manila1015, Philippines
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Zaher K, Basingab F. Interaction between Gut Microbiota and Dendritic Cells in Colorectal Cancer. Biomedicines 2023; 11:3196. [PMID: 38137417 PMCID: PMC10741039 DOI: 10.3390/biomedicines11123196] [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: 10/07/2023] [Revised: 11/07/2023] [Accepted: 11/14/2023] [Indexed: 12/24/2023] Open
Abstract
Colorectal cancer (CRC) is a malignancy that manifests in serial stages and has been observed to have an escalating incidence in modern societies, causing a significant global health problem. The development of CRC is influenced by various exogenous factors, including lifestyle, diet, nutrition, environment, and microbiota, that can affect host cells, including immune cells. Various immune dysfunctions have been recognized in patients with CRC at different stages of this disease. The signature of microbiota in the development of CRC-inflammation related to obesity, diet, and reactive host cells, such as dendritic cells (DCs)-has been highlighted by many studies. This study focuses on DCs, the primary cellular mediators linking innate and adaptive immune responses against cancer. In addition, this review focuses on the role of microbiota in dysbiosis and how it affects DCs and, in turn, the immune response and progression of CRC by stimulating different sets of T cells. Additionally, DCs' role in protecting this delicate balance is examined. This is to determine how gene yields of commensal microbiota may be critical in restoring this balance when disrupted. The stages of the disease and major checkpoints are discussed, as well as the role of the C-type lectin receptor of immature DCs pattern recognition receptor in CRC. Finally, based on a thorough examination of worldwide clinical studies and recent advancements in cancer immunotherapy, it is recommended that innovative approaches that integrate DC vaccination strategies with checkpoint inhibitors be considered. This approach holds great promise for improving CRC management.
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Affiliation(s)
- Kawther Zaher
- Immunology Unit, King Fahad Medical Research Centre, King Abdulaziz University, Jeddah 21859, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21859, Saudi Arabia
| | - Fatemah Basingab
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21585, Saudi Arabia
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Tian Z, Deng T, Gui X, Wang L, Yan Q, Wang L. Mechanisms of Lung and Intestinal Microbiota and Innate Immune Changes Caused by Pathogenic Enterococcus Faecalis Promoting the Development of Pediatric Pneumonia. Microorganisms 2023; 11:2203. [PMID: 37764047 PMCID: PMC10536929 DOI: 10.3390/microorganisms11092203] [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: 07/04/2023] [Revised: 08/15/2023] [Accepted: 08/16/2023] [Indexed: 09/29/2023] Open
Abstract
Bacterial pneumonia is the main cause of illness and death in children under 5 years old. We isolated and cultured pathogenic bacteria LE from the intestines of children with pneumonia and replicated the pediatric pneumonia model using an oral gavage bacterial animal model. Interestingly, based on 16srRNA sequencing, we found that the gut and lung microbiota showed the same imbalance trend, which weakened the natural resistance of this area. Further exploration of its mechanism revealed that the disruption of the intestinal mechanical barrier led to the activation of inflammatory factors IL-6 and IL-17, which promoted the recruitment of ILC-3 and the release of IL-17 and IL-22, leading to lung inflammation. The focus of this study is on the premise that the gut and lung microbiota exhibit similar destructive changes, mediating the innate immune response to promote the occurrence of pneumonia and providing a basis for the development and treatment of new drugs for pediatric pneumonia.
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Affiliation(s)
- Zhiying Tian
- Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian 116011, China;
| | - Ting Deng
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (T.D.); (X.G.); (L.W.)
| | - Xuwen Gui
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (T.D.); (X.G.); (L.W.)
| | - Leilei Wang
- Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian 116044, China; (T.D.); (X.G.); (L.W.)
| | - Qiulong Yan
- Department of Biochemistry and Molecular Biology, College of Basic Medicine, Dalian Medical University, Dalian 116044, China;
| | - Liang Wang
- Stem Cell Clinical Research Center, National Joint Engineering Laboratory, Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, No. 193, Lianhe Road, Shahekou District, Dalian 116011, China;
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Karki S, Mainali A, Pandey S, Uprety N, Panigrahi K, Adhikari S. Veillonella Bacteremia in a Patient With Metastatic Colorectal Carcinoma. Cureus 2023; 15:e41152. [PMID: 37519587 PMCID: PMC10386893 DOI: 10.7759/cureus.41152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/29/2023] [Indexed: 08/01/2023] Open
Abstract
Colorectal carcinoma has increasingly been reported to be associated with gut microbial dysbiosis. Bacteroides, Fusobacterium, Faecalibacterium, Blautia, etc., are gut microbes commonly associated with colorectal carcinoma. Gut microbial dysregulation secondary to infectious, inflammatory, toxin exposure or change in dietary habits coupled with the disruption of the inner mucosal layer overlying the luminal epithelium is hypothesized as the inciting events leading to microbial invasion and subsequent tumorigenesis. Although the precise mechanism is unclear, disruption of normal host responses like inflammation, apoptosis, cellular proliferation, free radical injury, production of oncogenic toxins, etc., is postulated to play a role. We report a case of Veillonella bacteremia in a patient with metastatic colorectal carcinoma without a preceding history of periodontal disease. The patient was managed with ampicillin-sulbactam, which was followed by subsequent negative blood cultures. This case report signifies the association of gut microbiota like Veillonella with colorectal carcinoma and the importance of subsequent screening for colorectal cancer following Veillonella bacteremia.
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Affiliation(s)
- Sailesh Karki
- Internal Medicine, One Brooklyn Health-Interfaith Medical Center, Brooklyn, USA
| | - Arjun Mainali
- Internal Medicine, One Brooklyn Health-Interfaith Medical Center, Brooklyn, USA
| | - Sagar Pandey
- Internal Medicine, One Brooklyn Health-Interfaith Medical Center, Brooklyn, USA
| | - Navodita Uprety
- Internal Medicine, One Brooklyn Health-Interfaith Medical Center, Brooklyn, USA
| | - Kalpana Panigrahi
- Internal Medicine, One Brooklyn Health-Interfaith Medical Center, Brooklyn, USA
| | - Samaj Adhikari
- Internal Medicine, One Brooklyn Health-Interfaith Medical Center, Brooklyn, USA
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Biotherapy Using Probiotics as Therapeutic Agents to Restore the Gut Microbiota to Relieve Gastrointestinal Tract Inflammation, IBD, IBS and Prevent Induction of Cancer. Int J Mol Sci 2023; 24:ijms24065748. [PMID: 36982816 PMCID: PMC10052502 DOI: 10.3390/ijms24065748] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 03/08/2023] [Accepted: 03/15/2023] [Indexed: 03/19/2023] Open
Abstract
The gut microbiota is composed of several microbial strains with diverse and variable compositions in both healthy and sick people. An undisturbed gut microbiota needs to be sustained in order to perform all physiological, metabolic, and immune functions in a normal way to prevent the development of diseases. This article has reviewed the published information on the issue of disruption of the balance of the gut microbiota. This disruption could be for many reasons, such as microbial infection in the gastrointestinal tract, food poisoning, diarrhoea, chemotherapy, malnutrition, lifestyle, and ageing. If this disruption is not restored to normal, it might cause dysbiosis. Eventually, a gut microbiota interrupted by dysbiosis might initiate several health issues, such as inflammation of the gastrointestinal tract, the induction of cancer, and the progression of a variety of diseases such as irritable bowel syndrome and inflammatory bowel disease. This review concluded that biotherapy is a natural way of using probiotic products, whether in form of food, beverages, or supplements, to restore the gut microbiota disrupted by dysbiosis. Metabolites secreted by the ingested probiotics help to relieve gastrointestinal tract inflammation and can avoid the induction of cancer.
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Maynard CL. The Microbiota in Immunity and Inflammation. Clin Immunol 2023. [DOI: 10.1016/b978-0-7020-8165-1.00022-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
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Quazi S. Anti-cancer activity of human gastrointestinal bacteria. Med Oncol 2022; 39:220. [PMID: 36175586 DOI: 10.1007/s12032-022-01771-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 06/14/2022] [Indexed: 06/16/2023]
Abstract
Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human's gastrointestinal tract can create immune response against inflammation and also can develop diseases, including cancer. The bacteria of the gastrointestinal tract of human can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.
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Affiliation(s)
- Sameer Quazi
- GenLab Biosolutions Private Limited, Bangalore, 560043, Karnataka, India.
- Department of Biomedical Sciences, School of Life Sciences, Anglia Ruskin University, Cambridge, UK.
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Zhou X, Matskova L, Zheng S, Wang X, Wang Y, Xiao X, Mo Y, Wölke M, Li L, Zheng Q, Huang G, Zhang Z, Ernberg I. Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation. Front Cell Dev Biol 2022; 10:861916. [PMID: 35938161 PMCID: PMC9353648 DOI: 10.3389/fcell.2022.861916] [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: 01/25/2022] [Accepted: 06/15/2022] [Indexed: 11/29/2022] Open
Abstract
Commensal microbes cross talk with their colonized mucosa. We show that microbes and their cell wall components induce an inflammatory response in cultured human mucosal cells derived from the nonmalignant nasopharyngeal epithelium (NNE) cells in vitro. NNE cells show significant induction of NF-κB with nuclear shuttling and inflammatory gene response when exposed to Gram-positive bacteria (streptococci) or peptidoglycan (PGN), a component of the Gram-positive bacterial cell wall. This response is abrogated in nasopharyngeal carcinoma (NPC)–derived cell lines. The inflammatory response induced by NF-κB signaling was blocked at two levels in the tumor-derived cells. We found that NF-κB was largely trapped in lipid droplets (LDs) in the cytoplasm of the NPC-derived cells, while the increased expression of lysine-specific histone demethylase 1 (LSD1, a repressive nuclear factor) reduces the response mediated by remaining NF-κB at the promoters responding to inflammatory stimuli. This refractory response in NPC cells might be a consequence of long-term exposure to microbes in vivo during carcinogenic progression. It may contribute to the decreased antitumor immune responses in NPC, among others despite heavy T-helper cell infiltration, and thus facilitate tumor progression.
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Affiliation(s)
- Xiaoying Zhou
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
- Life Science Institute, Guangxi Medical University, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, China
| | - Liudmila Matskova
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
| | - Shixing Zheng
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
- ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai, China
| | - Xiaoxia Wang
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
| | - Yifang Wang
- Life Science Institute, Guangxi Medical University, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, China
| | - Xue Xiao
- Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yingxi Mo
- Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Marleen Wölke
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
| | - Limei Li
- Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, China
| | - Qian Zheng
- Life Science Institute, Guangxi Medical University, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, China
| | - Guangwu Huang
- Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, China
- Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhe Zhang
- Key Laboratory of Early Prevention and Treatment for Regional High-Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, China
- ENT Institute and Department of Otorhinolaryngology, Eye and ENT Hospital, Fudan University, Shanghai, China
| | - Ingemar Ernberg
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden
- *Correspondence: Ingemar Ernberg,
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12
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Evaluation of Enterococcus faecalis, Lactobacillus acidophilus, and Lactobacillus plantarum in Biopsy Samples of Colorectal Cancer and Polyp Patients Compared to Healthy People. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2022. [DOI: 10.5812/archcid-116165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Colorectal cancer (CRC) is one of the leading causes of death in both men and women worldwide. According to different studies, infectious agents or microbiota dysbiosis can play a role in CRC progression. Objective: This study aimed to evaluate the prevalence of Enterococcus faecalis, Lactobacillus acidophilus, and Lactobacillus plantarum in people with polyps or CRC compared to healthy individuals. Methods: In this study, 60 biopsy samples were collected from three groups, including patients with CRC, polyps, and healthy people. The genomic DNA was extracted from the collected samples and amplified by polymerase chain reaction (PCR) to detect E. faecalis, L. acidophilus, and L. plantarum. In the next step, quantitative Real-Time PCR was used to evaluate the copy number of the bacteria in the studied groups. Results: There was no statistically significant difference between the studied groups regarding age and gender (P > 0.05). The mean number of E. faecalis was higher in patients with CRC than in patients with polyps and healthy individuals (P < 0.05). Also, the mean numbers of L. acidophilus and L. plantarum were higher in healthy individuals than in patients with polyps and CRC (P < 0.05). Conclusions: Our findings indicate that L. acidophilus and L. plantarum in people with a family history of CRC and patients with polyps may effectively prevent or reduce CRC progression.
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13
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Ahmad S, Ashktorab H, Brim H, Housseau F. Inflammation, microbiome and colorectal cancer disparity in African-Americans: Are there bugs in the genetics? World J Gastroenterol 2022; 28:2782-2801. [PMID: 35978869 PMCID: PMC9280725 DOI: 10.3748/wjg.v28.i25.2782] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 01/27/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Dysregulated interactions between host inflammation and gut microbiota over the course of life increase the risk of colorectal cancer (CRC). While environmental factors and socio-economic realities of race remain predominant contributors to CRC disparities in African-Americans (AAs), this review focuses on the biological mediators of CRC disparity, namely the under-appreciated influence of inherited ancestral genetic regulation on mucosal innate immunity and its interaction with the microbiome. There remains a poor understanding of mechanisms linking immune-related genetic polymorphisms and microbiome diversity that could influence chronic inflammation and exacerbate CRC disparities in AAs. A better understanding of the relationship between host genetics, bacteria, and CRC pathogenesis will improve the prediction of cancer risk across race/ethnicity groups overall.
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Affiliation(s)
- Sami Ahmad
- Department of Oncology, Johns Hopkins University, Baltimore, MD 21231, United States
| | - Hassan Ashktorab
- Department of Medicine, Howard University, Washington, DC 20060, United States
| | - Hassan Brim
- Department of Pathology, Howard University, Washington, DC 20060, United States
| | - Franck Housseau
- Department of Oncology, Johns Hopkins University, Baltimore, MD 21231, United States
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14
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Sadrekarimi H, Gardanova ZR, Bakhshesh M, Ebrahimzadeh F, Yaseri AF, Thangavelu L, Hasanpoor Z, Zadeh FA, Kahrizi MS. Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora. Lab Invest 2022; 20:301. [PMID: 35794566 PMCID: PMC9258144 DOI: 10.1186/s12967-022-03492-7] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022]
Abstract
In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches’ therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.
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15
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Biswas P, Pal S, Das M, Dam S. Microbe-Induced Oxidative Stress in Cancer Development and Efficacy of Probiotics as Therapeutics in Preventing Its Onset and Progression. HANDBOOK OF OXIDATIVE STRESS IN CANCER: THERAPEUTIC ASPECTS 2022:3513-3542. [DOI: 10.1007/978-981-16-5422-0_159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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16
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Van der Meer J, Mamouris P, Nassiri V, Vaes B, van den Akker M. Use of antibiotics and colorectal cancer risk: a primary care nested case-control study in Belgium. BMJ Open 2021; 11:e053511. [PMID: 34893485 PMCID: PMC8666897 DOI: 10.1136/bmjopen-2021-053511] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVES To examine the association between the use of oral antibiotics and subsequent colorectal cancer risk. DESIGN Matched case-control study. SETTING General practice centres participating in the Integrated Computerised Network database in Flanders, Belgium. PARTICIPANTS In total, 1705 cases of colorectal cancer diagnosed between 01 January 2010 and 31 December 2015 were matched to 6749 controls by age, sex, comorbidity and general practice centre. PRIMARY OUTCOME MEASURE The association between the number of prescriptions for oral antibiotics and the incidence of colorectal cancer over a period of 1-10 years, estimated by a conditional logistic regression model. RESULTS A significantly increased risk of colorectal cancer (OR 1.25, 95% CI 1.10 to 1.44) was found in subjects with one or more prescriptions compared with those with none after correction for diabetes mellitus. No dose-response relationship was found. CONCLUSIONS This study resulted in a modestly higher risk of having colorectal cancer diagnosed after antibiotic exposure. The main limitation was missing data on known risk factors, in particular smoking behaviour. This study did not allow us to examine the causality of the relationship, indicating the need of further investigation.
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Affiliation(s)
- Johannes Van der Meer
- Department of Public Health and Primary Care, Academic Centre for General Practice, KU Leuven Biomedical Sciences Group, Leuven, Flanders, Belgium
| | - Pavlos Mamouris
- Departement of Public Health and Primary Care, Katholieke Universiteit Leuven Groep Biomedische Wetenschappen, Leuven, Belgium
| | | | - Bert Vaes
- Departement of Public Health and Primary Care, Katholieke Universiteit Leuven Groep Biomedische Wetenschappen, Leuven, Belgium
| | - Marjan van den Akker
- Department of Public Health and Primary Care, KU Leuven Biomedical Sciences Group, Leuven, Flanders, Belgium
- Institute of General Practice, Goethe University Frankfurt Faculty 16 Medicine, Frankfurt am Main, Hessen, Germany
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17
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Dong J, Li Y, Xiao H, Cui M, Fan S. Commensal microbiota in the digestive tract: a review of its roles in carcinogenesis and radiotherapy. Cancer Biol Med 2021; 19:j.issn.2095-3941.2020.0476. [PMID: 34369136 PMCID: PMC8763002 DOI: 10.20892/j.issn.2095-3941.2020.0476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 01/27/2021] [Indexed: 11/11/2022] Open
Abstract
The human microflora is a complex ecosystem composed of diverse microorganisms mainly distributed in the epidermal and mucosal habitats of the entire body, including the mouth, lung, intestines, skin, and vagina. These microbial communities are involved in many essential functions, such as metabolism, immunity, host nutrition, and diseases. Recent studies have focused on the microbiota associated with cancers, particularly the oral and intestinal microbiota. Radiotherapy, the most effective cytotoxic modality available for solid tumors, contributes to the treatment of cancer patients. Mounting evidence supports that the microbiota plays pivotal roles in the efficacy and prognosis of tumor radiotherapy. Here, we review current research on the microbiota and cancer development, and describe knowledge gaps in the study of radiotherapy and the microbiota. Better understanding of the effects of the microbiome in tumorigenesis and radiotherapy will shed light on future novel prevention and treatment strategies based on modulating the microbiome in cancer patients.
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Affiliation(s)
- Jiali Dong
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
| | - Yuan Li
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
| | - Huiwen Xiao
- Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
| | - Ming Cui
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
| | - Saijun Fan
- Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China
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18
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Ren L, Ye J, Zhao B, Sun J, Cao P, Yang Y. The Role of Intestinal Microbiota in Colorectal Cancer. Front Pharmacol 2021; 12:674807. [PMID: 33959032 PMCID: PMC8093878 DOI: 10.3389/fphar.2021.674807] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 03/23/2021] [Indexed: 12/15/2022] Open
Abstract
Colorectal cancer is a multifactorial disease involving genetic, environmental, and lifestyle risk factors. Intestinal microbiota plays an important role in the occurrence and development of colorectal cancer. Studies have shown that the behavior of intestinal microbiota can lead to pathological changes in the host intestine, which can be divided into epigenetic changes and carcinogenic changes at the gene level, and ultimately promote the formation and development of colorectal cancer. Intestinal microbiota is mainly distributed in the intestinal epithelium, which is composed of a large number of microorganisms interacting with the host intestinal cells. It can affect the immune-inflammation and metabolism of the gastrointestinal tract, and may be used as a biomarker for disease diagnosis. Regulation of gut microbiota is a promising strategy for the prevention and treatment of colorectal cancer. This article reviews the role of intestinal microbiota in the development of colorectal cancer, including the related mechanisms of intestinal microbiota promoting colorectal cancer, the use of intestinal microbiota in the diagnosis of colorectal cancer, and the regulation of intestinal microbiota in the prevention or treatment of colorectal cancer.
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Affiliation(s)
- Lingli Ren
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Juan Ye
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Bing Zhao
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jinbing Sun
- Department of General Surgery, Changshu No. 1 People's Hospital, Affiliated Changshu Hospital of Soochow University, Changshu, China
| | - Peng Cao
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yang Yang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.,Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.,Yangtze River Pharmaceutical Group, Taizhou, China
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19
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Li W, Deng X, Chen T. Exploring the Modulatory Effects of Gut Microbiota in Anti-Cancer Therapy. Front Oncol 2021; 11:644454. [PMID: 33928033 PMCID: PMC8076595 DOI: 10.3389/fonc.2021.644454] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 03/18/2021] [Indexed: 12/16/2022] Open
Abstract
In the recent decade, gut microbiota has received growing interest due to its role in human health and disease. On the one hand, by utilizing the signaling pathways of the host and interacting with the immune system, the gut microbiota is able to maintain the homeostasis in human body. This important role is mainly modulated by the composition of microbiota, as a normal microbiota composition is responsible for maintaining the homeostasis of human body, while an altered microbiota profile could contribute to several pathogenic conditions and may further lead to oncogenesis and tumor progression. Moreover, recent insights have especially focused on the important role of gut microbiota in current anticancer therapies, including chemotherapy, radiotherapy, immunotherapy and surgery. Research findings have indicated a bidirectional interplay between gut microbiota and these therapeutic methods, in which the implementation of different therapeutic methods could lead to different alterations in gut microbiota, and the presence of gut microbiota could in turn contribute to different therapeutic responses. As a result, manipulating the gut microbiota to reduce the therapy-induced toxicity may provide an adjuvant therapy to achieve a better therapeutic outcome. Given the complex role of gut microbiota in cancer treatment, this review summarizes the interactions between gut microbiota and anticancer therapies, and demonstrates the current strategies for reshaping gut microbiota community, aiming to provide possibilities for finding an alternative approach to lower the damage and improve the efficacy of cancer therapy.
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Affiliation(s)
- Wenyu Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Queen Mary School, Nanchang University, Nanchang, China
| | - Xiaorong Deng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Tingtao Chen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, The First Affiliated Hospital, Nanchang University, Nanchang, China
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20
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Ladaycia A, Loretz B, Passirani C, Lehr CM, Lepeltier E. Microbiota and cancer: In vitro and in vivo models to evaluate nanomedicines. Adv Drug Deliv Rev 2021; 170:44-70. [PMID: 33388279 DOI: 10.1016/j.addr.2020.12.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 12/23/2020] [Accepted: 12/27/2020] [Indexed: 02/08/2023]
Abstract
Nanomedicine implication in cancer treatment and diagnosis studies witness huge attention, especially with the promising results obtained in preclinical studies. Despite this, only few nanomedicines succeeded to pass clinical phase. The human microbiota plays obvious roles in cancer development. Nanoparticles have been successfully used to modulate human microbiota and notably tumor associated microbiota. Taking the microbiota involvement under consideration when testing nanomedicines for cancer treatment might be a way to improve the poor translation from preclinical to clinical trials. Co-culture models of bacteria and cancer cells, as well as animal cancer-microbiota models offer a better representation for the tumor microenvironment and so potentially better platforms to test nanomedicine efficacy in cancer treatment. These models would allow closer representation of human cancer and might smoothen the passage from preclinical to clinical cancer studies for nanomedicine efficacy.
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21
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Parida S, Wu S, Siddharth S, Wang G, Muniraj N, Nagalingam A, Hum C, Mistriotis P, Hao H, Talbot CC, Konstantopoulos K, Gabrielson KL, Sears CL, Sharma D. A Procarcinogenic Colon Microbe Promotes Breast Tumorigenesis and Metastatic Progression and Concomitantly Activates Notch and β-Catenin Axes. Cancer Discov 2021; 11:1138-1157. [PMID: 33408241 DOI: 10.1158/2159-8290.cd-20-0537] [Citation(s) in RCA: 112] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Revised: 11/03/2020] [Accepted: 12/07/2020] [Indexed: 11/16/2022]
Abstract
The existence of distinct breast microbiota has been recently established, but their biological impact in breast cancer remains elusive. Focusing on the shift in microbial community composition in diseased breast compared with normal breast, we identified the presence of Bacteroides fragilis in cancerous breast. Mammary gland as well as gut colonization with enterotoxigenic Bacteroides fragilis (ETBF), which secretes B. fragilis toxin (BFT), rapidly induces epithelial hyperplasia in the mammary gland. Breast cancer cells exposed to BFT exhibit "BFT memory" from the initial exposure. Intriguingly, gut or breast duct colonization with ETBF strongly induces growth and metastatic progression of tumor cells implanted in mammary ducts, in contrast to nontoxigenic Bacteroides fragilis. This work sheds light on the oncogenic impact of a procarcinogenic colon bacterium ETBF on breast cancer progression, implicates the β-catenin and Notch1 axis as its functional mediators, and proposes the concept of "BFT memory" that can have far-reaching biological implications after initial exposure to ETBF. SIGNIFICANCE: B. fragilis is an inhabitant of breast tissue, and gut or mammary duct colonization with ETBF triggers epithelial hyperplasia and augments breast cancer growth and metastasis. Short-term exposure to BFT elicits a "BFT memory" with long-term implications, functionally mediated by the β-catenin and Notch1 pathways.This article is highlighted in the In This Issue feature, p. 995.
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Affiliation(s)
- Sheetal Parida
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shaoguang Wu
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sumit Siddharth
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Guannan Wang
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nethaji Muniraj
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Arumugam Nagalingam
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Christina Hum
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Panagiotis Mistriotis
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Haiping Hao
- Johns Hopkins Transcriptomics and Deep Sequencing Core, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - C Conover Talbot
- Johns Hopkins Transcriptomics and Deep Sequencing Core, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Konstantinos Konstantopoulos
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kathleen L Gabrielson
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Cynthia L Sears
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dipali Sharma
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
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22
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Beştaş R, Ekin N. Is gastric intestinal metaplasia a risk factor for colorectal neoplasms? BIOTECHNOL BIOTEC EQ 2021. [DOI: 10.1080/13102818.2021.1974945] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Affiliation(s)
- Remzi Beştaş
- Gastroenterology Department, Memorial Dicle Hospital, Diyarbakır, Turkey
| | - Nazım Ekin
- Gastroenterology Department, Diyarbakır Gazi Yaşargil Training and Research Hospital, Health Sciences University, Diyarbakır, Turkey
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23
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Butt J, Jenab M, Werner J, Fedirko V, Weiderpass E, Dahm CC, Tjønneland A, Olsen A, Boutron-Ruault MC, Rothwell JA, Severi G, Kaaks R, Turzanski-Fortner R, Aleksandrova K, Schulze M, Palli D, Pala V, Panico S, Tumino R, Sacerdote C, Bueno-de-Mesquita B, Van Gils CH, Gram IT, Lukic M, Sala N, Sánchez Pérez MJ, Ardanaz E, Chirlaque MD, Palmquist R, Löwenmark T, Travis RC, Heath A, Cross AJ, Freisling H, Zouiouich S, Aglago E, Waterboer T, Hughes DJ. Association of Pre-diagnostic Antibody Responses to Escherichia coli and Bacteroides fragilis Toxin Proteins with Colorectal Cancer in a European Cohort. Gut Microbes 2021; 13:1-14. [PMID: 33874856 PMCID: PMC8078709 DOI: 10.1080/19490976.2021.1903825] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 02/25/2021] [Accepted: 03/02/2021] [Indexed: 02/07/2023] Open
Abstract
Experimental evidence has implicated genotoxic Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of E. coli and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study.Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven E. coli proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to E. coli and ETBF with CRC.The IgA-positivity of any of the tested E. coli antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05-1.91). Dual-positivity for both IgA and IgG to E. coli and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (pheterogeneity = 0.095). Sero-positivity to E. coli and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups.
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Affiliation(s)
- Julia Butt
- Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Mazda Jenab
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Jill Werner
- Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Veronika Fedirko
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | | | - Christina C. Dahm
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Anne Tjønneland
- Exposome and Heredity Team, CESP (Centre de Recherche en Epidemiologie et Santé des Populations), Diet, Genes and Environment, Nutrition and Biomarkers (NAB), Danish Cancer Society Research Center, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, Denmark
| | - Anja Olsen
- Exposome and Heredity Team, CESP (Centre de Recherche en Epidemiologie et Santé des Populations), Diet, Genes and Environment, Nutrition and Biomarkers (NAB), Danish Cancer Society Research Center, Copenhagen, Denmark
- Department of Public Health, University of Aarhus, Denmark
| | | | - Joseph A. Rothwell
- Cesp (Umr1018), Médecine Université Paris-Saclay, Inserm, Gustave Roussy, Villejuif, France
| | - Gianluca Severi
- Cesp (Umr1018), Médecine Université Paris-Saclay, Inserm, Gustave Roussy, Villejuif, France
- Department of Statistics, Computer Science and Applications (DISIA), University of Florence, Italy
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | - Krasimira Aleksandrova
- Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany
| | - Matthias Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
| | - Domenico Palli
- Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy
| | - Valeria Pala
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Salvatore Panico
- Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7), Ragusa, Italy
| | - Carlotta Sacerdote
- Unit of Cancer Epidemiology, Città Della Salute E Della Scienza University-Hospital, Turin, Italy
| | - Bas Bueno-de-Mesquita
- Former Senior Scientist, Dept. For Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Former Associate Professor, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
- Former Visiting Professor, Dept. Of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK
- Former Academic Icon/visiting Professor, Dept. Of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Carla H. Van Gils
- Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Inger Torhild Gram
- Department of Community Medicine, University of Tromsø, the Arctic University of Norway, Tromsø, Norway
| | - Marko Lukic
- Department of Community Medicine, UiT, The Arctic University of Norway, Tromsø, Norway
| | - Núria Sala
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program and Translational Research Laboratory, Catalan Institute of Oncology (ICO), Biomedical Research Institute (IDIBELL), Barcelona, Spain
| | - María José Sánchez Pérez
- Escuela Andaluza De Salud Pública (EASP), Granada, Spain
- Instituto De Investigación Biosanitaria ibs.GRANADA, Granada, Spain
- Centro De Investigación Biomédica En Red De Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain
| | - Eva Ardanaz
- Navarra Public Health Institute, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
- CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain
| | - María-Dolores Chirlaque
- Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain
- CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Richard Palmquist
- Department of Medical Biosciences, Pathology, Umeå University, Ireland
| | - Thyra Löwenmark
- Department of Medical Biosciences, Pathology, Umeå University, Ireland
| | - Ruth C Travis
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Alicia Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Amanda J Cross
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Heinz Freisling
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Semi Zouiouich
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Elom Aglago
- International Agency for Research on Cancer (IARC-WHO), Lyon, France
| | - Tim Waterboer
- Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - David J. Hughes
- Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland
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24
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Xu N, Wang L, Li C, Ding C, Li C, Fan W, Cheng C, Gu B. Microbiota dysbiosis in lung cancer: evidence of association and potential mechanisms. Transl Lung Cancer Res 2020; 9:1554-1568. [PMID: 32953527 PMCID: PMC7481604 DOI: 10.21037/tlcr-20-156] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 06/10/2020] [Indexed: 12/11/2022]
Abstract
Over the past decade, revolution in microbial research has provided valuable insights into the function of microbes that inhabit human body. This complex community of microbes, collectively named as microbiota, displays tremendous interaction with a host to maintain homeostasis of the local environment. Lungs were even previously regarded as sterile for a long time. With the development of high-throughput next-generation sequencing technology, a low-density, diversified microbial ecosystem is found in bronchoalveolar lavage fluid, sputum, and lung tissues. Current research confirms that, compared with healthy people, patients with lung cancer show changes in the relative abundance of multiple genera. Emerging evidence has suggested that dysbiosis of the lung microbiota may play a critical role in lung carcinogenesis by affecting metabolic, inflammatory pathways and immune response. We briefly summarize the relationship between lung microbiome and lung cancer and discuss the potential mechanisms mediating lung microbiota and lung cancer. Thus, we provide innovative strategies for early prevention and personalized treatment of lung cancer.
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Affiliation(s)
- Nana Xu
- Laboratory of Morphology, Xuzhou Medical University, Xuzhou, China
| | - Lei Wang
- Department of Histology and Embryology, Xuzhou Medical University, Xuzhou, China
| | - Chenxi Li
- Medical Technology Institute of Xuzhou Medical University, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou, China
| | - Chao Ding
- Department of General Surgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Cong Li
- Emergency Intensive Care Unit, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Wenting Fan
- Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Chen Cheng
- Medical Technology Institute of Xuzhou Medical University, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou, China
| | - Bing Gu
- Medical Technology Institute of Xuzhou Medical University, Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou, China
- Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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25
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Uttam S, Stern AM, Sevinsky CJ, Furman S, Pullara F, Spagnolo D, Nguyen L, Gough A, Ginty F, Lansing Taylor D, Chakra Chennubhotla S. Spatial domain analysis predicts risk of colorectal cancer recurrence and infers associated tumor microenvironment networks. Nat Commun 2020; 11:3515. [PMID: 32665557 PMCID: PMC7360741 DOI: 10.1038/s41467-020-17083-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 06/03/2020] [Indexed: 12/17/2022] Open
Abstract
An unmet clinical need in solid tumor cancers is the ability to harness the intrinsic spatial information in primary tumors that can be exploited to optimize prognostics, diagnostics and therapeutic strategies for precision medicine. Here, we develop a transformational spatial analytics computational and systems biology platform (SpAn) that predicts clinical outcomes and captures emergent spatial biology that can potentially inform therapeutic strategies. We apply SpAn to primary tumor tissue samples from a cohort of 432 chemo-naïve colorectal cancer (CRC) patients iteratively labeled with a highly multiplexed (hyperplexed) panel of 55 fluorescently tagged antibodies. We show that SpAn predicts the 5-year risk of CRC recurrence with a mean AUROC of 88.5% (SE of 0.1%), significantly better than current state-of-the-art methods. Additionally, SpAn infers the emergent network biology of tumor microenvironment spatial domains revealing a spatially-mediated role of CRC consensus molecular subtype features with the potential to inform precision medicine.
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Affiliation(s)
- Shikhar Uttam
- Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
| | - Andrew M Stern
- Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
- University of Pittsburgh Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA
| | | | - Samantha Furman
- Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Filippo Pullara
- Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Daniel Spagnolo
- Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Luong Nguyen
- Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Albert Gough
- Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
- University of Pittsburgh Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA
| | - Fiona Ginty
- Biology and Applied Physics, GE Global Research Center, Niskayuna, NY, 12309, USA
| | - D Lansing Taylor
- Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
- University of Pittsburgh Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA, 15261, USA
| | - S Chakra Chennubhotla
- Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
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26
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Mohamed AK, Elhassan NM, Awhag ZA, Ali FS, Ali ET, Mhmoud NA, Siddig EE, Hassan R, Ahmed ES, Fattahi A, Ahmed A, Muneer MS, Osman HA, Mohamed NS, Edris AMM. Prevalence of Helicobacter pylori among Sudanese patients diagnosed with colon polyps and colon cancer using immunohistochemistry technique. BMC Res Notes 2020; 13:322. [PMID: 32631443 PMCID: PMC7339555 DOI: 10.1186/s13104-020-05159-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 06/26/2020] [Indexed: 12/12/2022] Open
Abstract
Objectives Infection with the bacteria Helicobacter pylori has been classified as class one carcinogen associated with increasing susceptibility of gastritis and gastric carcinoma. This study is aiming at investigating the prevalence of H. pylori among colon polyps and colon cancer patients. A descriptive cross-sectional hospital-based study was conducted between February and June 2017. Sixty-nine formalin-fixed paraffin blocks collected from colon polyps and colon cancer patients to detect H. pylori using immunohistochemistry technique. Results Of the 69 patients included in the study, 39 (56.5%) males and 30 (43.5%) were females, their age ranged from 21 to 80 years with a mean age of 47.1 ± 19.7. Of the 69 colon polyps and colon cancer patients, 44 (63.8%) were diagnosed as adenocarcinoma, 10 (14.5%) colitis, 15 (21.7%) juvenile polyposis syndrome. The results of immunohistochemistry technique showed the presence of 16 (23.2%) positive patients for H. pylori infection. Of these 16, 13 (81.3%) patients were diagnosed with adenocarcinoma and 3 (18.7%) patients were diagnosed with juvenile polyps. The results of H. pylori detection among the different colon polyps and colon cancer patients were showing a statistically significant association for H. pylori infection and adenocarcinoma, P value 0.028.
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Affiliation(s)
- Aziza K Mohamed
- Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan
| | - Nazik M Elhassan
- Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan
| | - Zahra A Awhag
- Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan
| | - Fadwa S Ali
- Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan
| | - Eman T Ali
- Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan.,Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, National University, Sudan, Khartoum, Sudan
| | - Najwa A Mhmoud
- Mycetoma Research Center, University of Khartoum, Khartoum, Sudan.,Department of Microbiology and Immunology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan
| | - Emmanuel E Siddig
- Mycetoma Research Center, University of Khartoum, Khartoum, Sudan.,School of Medicine, Nile University, Khartoum, Sudan.,Department of Histopathology and Cytology, Alfarrabi College for Science and Technology, Khartoum, Sudan
| | - Rowa Hassan
- Mycetoma Research Center, University of Khartoum, Khartoum, Sudan
| | - Eiman S Ahmed
- Mycetoma Research Center, University of Khartoum, Khartoum, Sudan
| | - Azam Fattahi
- Center for Research and Training in Skin Disease and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
| | - Ayman Ahmed
- Department of Parasitology and Medical Entomology, Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan
| | - Mohamed S Muneer
- Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.,Department of Radiology, Mayo Clinic, Jacksonville, FL, USA.,Department of Internal Medicine, Faculty of Medicine, University of Khartoum, Khartoum, Sudan
| | - Hussam A Osman
- Biomedical Research Laboratory, Ahfad University for Women, Omdurman, Sudan
| | - Nouh S Mohamed
- Molecular Biology Department, Alfarrabi College for sciences and Technology, Khartoum, Sudan. .,Department of Parasitology and Medical Entomology, Faculty of Medicine, Sinnar University, Sinnar, Sudan. .,Department of Parasitology and Medical Entomology, Faculty of Medical Laboratory Sciences, Nile University, Khartoum, Sudan.
| | - Ali M M Edris
- Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan.,Faculty of Applied Medical Sciences, University of Bisha, Bisha, Kingdom of Saudi Arabia
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27
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Ganesan K, Jayachandran M, Xu B. Diet-Derived Phytochemicals Targeting Colon Cancer Stem Cells and Microbiota in Colorectal Cancer. Int J Mol Sci 2020; 21:E3976. [PMID: 32492917 PMCID: PMC7312951 DOI: 10.3390/ijms21113976] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 05/28/2020] [Accepted: 05/30/2020] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a fatal disease caused by the uncontrolled propagation and endurance of atypical colon cells. A person's lifestyle and eating pattern have significant impacts on the CRC in a positive and/or negative way. Diet-derived phytochemicals modulate the microbiome as well as targeting colon cancer stem cells (CSCs) that are found to offer significant protective effects against CRC, which were organized in an appropriate spot on the paper. All information on dietary phytochemicals, gut microbiome, CSCs, and their influence on CRC were accessed from the various databases and electronic search engines. The effectiveness of CRC can be reduced using various dietary phytochemicals or modulating microbiome that reduces or inverses the progression of a tumor as well as CSCs, which could be a promising and efficient way to reduce the burden of CRC. Phytochemicals with modulation of gut microbiome continue to be auspicious investigations in CRC through noticeable anti-tumorigenic effects and goals to CSCs, which provides new openings for cancer inhibition and treatment.
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Affiliation(s)
- Kumar Ganesan
- Food Science and Technology Programme, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China; (K.G.); (M.J.)
- Laboratory and Clinical Research Institute for Pain, Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China
| | - Muthukumaran Jayachandran
- Food Science and Technology Programme, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China; (K.G.); (M.J.)
| | - Baojun Xu
- Food Science and Technology Programme, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China; (K.G.); (M.J.)
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28
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Garza DR, Taddese R, Wirbel J, Zeller G, Boleij A, Huynen MA, Dutilh BE. Metabolic models predict bacterial passengers in colorectal cancer. Cancer Metab 2020; 8:3. [PMID: 32055399 PMCID: PMC7008539 DOI: 10.1186/s40170-020-0208-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 01/07/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a complex multifactorial disease. Increasing evidence suggests that the microbiome is involved in different stages of CRC initiation and progression. Beyond specific pro-oncogenic mechanisms found in pathogens, metagenomic studies indicate the existence of a microbiome signature, where particular bacterial taxa are enriched in the metagenomes of CRC patients. Here, we investigate to what extent the abundance of bacterial taxa in CRC metagenomes can be explained by the growth advantage resulting from the presence of specific CRC metabolites in the tumor microenvironment. METHODS We composed lists of metabolites and bacteria that are enriched on CRC samples by reviewing metabolomics experimental literature and integrating data from metagenomic case-control studies. We computationally evaluated the growth effect of CRC enriched metabolites on over 1500 genome-based metabolic models of human microbiome bacteria. We integrated the metabolomics data and the mechanistic models by using scores that quantify the response of bacterial biomass production to CRC-enriched metabolites and used these scores to rank bacteria as potential CRC passengers. RESULTS We found that metabolic networks of bacteria that are significantly enriched in CRC metagenomic samples either depend on metabolites that are more abundant in CRC samples or specifically benefit from these metabolites for biomass production. This suggests that metabolic alterations in the cancer environment are a major component shaping the CRC microbiome. CONCLUSION Here, we show with in sillico models that supplementing the intestinal environment with CRC metabolites specifically predicts the outgrowth of CRC-associated bacteria. We thus mechanistically explain why a range of CRC passenger bacteria are associated with CRC, enhancing our understanding of this disease. Our methods are applicable to other microbial communities, since it allows the systematic investigation of how shifts in the microbiome can be explained from changes in the metabolome.
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Affiliation(s)
- Daniel R. Garza
- Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands
| | - Rahwa Taddese
- Department of Pathology, Radboud University Medical Center, Postbus 9101, 6500 Nijmegen, HB Netherlands
| | - Jakob Wirbel
- European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
| | - Georg Zeller
- European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany
| | - Annemarie Boleij
- Department of Pathology, Radboud University Medical Center, Postbus 9101, 6500 Nijmegen, HB Netherlands
| | - Martijn A. Huynen
- Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands
| | - Bas E. Dutilh
- Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands
- Theoretical Biology and Bioinformatics, Sience4Life, Utrecht University, Hugo R. Kruytgebouw, Room Z-509, Padualaan 8, Utrecht, The Netherlands
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29
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Peng M, Zheng Q, Liu P, Liang X, Zhang M, Wang Y, Zhao Y. Developments in the study of gastrointestinal microbiome disorders affected by FGF19 in the occurrence and development of colorectal neoplasms. J Cell Physiol 2019; 235:4060-4069. [PMID: 31637718 DOI: 10.1002/jcp.29322] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 09/30/2019] [Indexed: 12/15/2022]
Abstract
Colorectal neoplasms are a type of malignant digestive system tumor that has become the third-highest morbidity tumor in China and the fourth leading cause of cancer-related death worldwide. The role of the gastrointestinal (GI) microbiome in bile acid metabolism, inflammation, and insulin resistance and its strong correlation with the occurrence and development of colorectal neoplasms have gradually led to it becoming a target area of tumor research. Fibroblast growth factor (FGF) 19 is a hormone that is secreted in mainly the ileum and can regulate bile acid biosynthesis, improve inflammation, and regulate insulin resistance. The relationship of the GI microbiome, FGF19 and its carcinogenic activities in colorectal neoplasms enticed us to search for potential targets and research ideas for the clinical diagnosis and treatment of colorectal neoplasms.
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Affiliation(s)
- Meichang Peng
- Basic Medical School, Guangdong Medical University, Dongguan, Guangdong, China.,Second School of Clinical Medicine, Guangdong Medical University, Dongguan, Guangdong, China
| | - Qiaowen Zheng
- Basic Medical School, Guangdong Medical University, Dongguan, Guangdong, China
| | - Peiqi Liu
- Second School of Clinical Medicine, Guangdong Medical University, Dongguan, Guangdong, China
| | - Xinyun Liang
- Basic Medical School, Guangdong Medical University, Dongguan, Guangdong, China
| | - Min Zhang
- Basic Medical School, Guangdong Medical University, Dongguan, Guangdong, China
| | - Yan Wang
- Basic Medical School, Guangdong Medical University, Dongguan, Guangdong, China
| | - Yi Zhao
- Basic Medical School, Guangdong Medical University, Dongguan, Guangdong, China
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30
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Dai Z, Zhang J, Wu Q, Chen J, Liu J, Wang L, Chen C, Xu J, Zhang H, Shi C, Li Z, Fang H, Lin C, Tang D, Wang D. The role of microbiota in the development of colorectal cancer. Int J Cancer 2019; 145:2032-2041. [PMID: 30474116 PMCID: PMC6899977 DOI: 10.1002/ijc.32017] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 10/25/2018] [Accepted: 11/13/2018] [Indexed: 02/05/2023]
Abstract
Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.
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Affiliation(s)
- Zhujiang Dai
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Jingqiu Zhang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Qi Wu
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Juan Chen
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Jun Liu
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Lu Wang
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Chaowu Chen
- Department of GastroenterologyClinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Jiaming Xu
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Hongpeng Zhang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Chunfeng Shi
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Zhen Li
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Huiwen Fang
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Chaobiao Lin
- Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina
| | - Dong Tang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
| | - Daorong Wang
- Department of General SurgeryInstitute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's HospitalYangzhouChina
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31
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Helicobacter pylori infection coexisting with intestinal metaplasia is not associated with colorectal neoplasms. GASTROENTEROLOGY REVIEW 2019; 14:133-139. [PMID: 31616528 PMCID: PMC6791137 DOI: 10.5114/pg.2019.85897] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 11/21/2018] [Indexed: 12/14/2022]
Abstract
Introduction Colorectal cancer is one of the most common cancers and is a major cause of morbidity and mortality in the world and our country. Studies have indicated that there might be a relationship between Helicobacter pylori (Hp) and colorectal neoplasia (CN), although others have not found any relationship. Aim To determine whether there is a potential relationship between Hp and CN in our patients. Material and methods A total of 314 patients, aged 16–86 years, who underwent gastroscopy and colonoscopy at our department between 2015 and 2017 were evaluated retrospectively. The age, gender, endoscopy results, presence of Hp, complete blood count (CBC), vitamin B12, folic acid, C-reactive protein (CRP), and sedimentation levels of the patients were examined. Results CBC, ferritin, vitamin B12, and CRP measurements did not show statistical significance in terms of the presence of Hp (p > 0.05). Folate values of Hp-positive patients were significantly lower than Hp-negative patients (p = 0.007; p < 0.01). No significant relationship was detected between Hp and colon cancer (p > 0.05). Adenomatous polyps were not related to Hp (p > 0.05). Correlation between intestinal metaplasia (IM) and adenomatous polyps was insignificant. There was no statistically significant difference between colon and gastric pathology results. Conclusions In our study, no significant relationship was noted between Hp and CN. A few studies have been conducted in our country, and our results are consistent with some of these studies while it is contradictory to others. Large populational multicentre studies are needed in order to identify the relationship between Hp and CN.
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32
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Song W, Liu R, Huang L. Response to Comment on "Trapping of Lipopolysaccharide to Promote Immunotherapy against Colorectal Cancer and Attenuate Liver Metastasis". ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2019; 31:e1902569. [PMID: 31155768 DOI: 10.1002/adma.201902569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Indexed: 06/09/2023]
Affiliation(s)
- Wantong Song
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China
| | - Rihe Liu
- Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
| | - Leaf Huang
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
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Fung KY, Nguyen PM, Putoczki T. The expanding role of innate lymphoid cells and their T-cell counterparts in gastrointestinal cancers. Mol Immunol 2019; 110:48-56. [DOI: 10.1016/j.molimm.2017.11.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 11/14/2017] [Indexed: 02/08/2023]
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34
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Wu C, Ouyang M, Guo Q, Jia J, Liu R, Jiang Y, Wu M, Shen S. Changes in the intestinal microecology induced by bacillus subtilis inhibit the occurrence of ulcerative colitis and associated cancers: a study on the mechanisms. Am J Cancer Res 2019; 9:872-886. [PMID: 31218099 PMCID: PMC6556602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 04/26/2019] [Indexed: 06/09/2023] Open
Abstract
This study aimed to explore how changes in intestinal floras caused by Bacillus subtilis (Bs) inhibited occurrence of ulcerative colitis (UC) and associated cancers. Bs was used as an intervention in an azoxymethane (AOM)/dextran sodium sulfate sodium (DSS) animal model. Stool specimens were analyzed for changes in intestinal floras. Disease activity index (DAI) scores, body mass indices, cancer counts, and other indices were calculated, while changes in the colon mucosa were observed. Compared with AOM/DSS group, carcinogenesis significantly reduced and intestinal inflammations and DAI score alleviated; diversity, evenness, and number of species of floras significantly increased; and relative abundances of Rikenellaceae and Lactobacillus increased when UC developed into cancers in the AOM/DSS + Bs group. Colon epitheliums in the mice were severely damaged in the AOM/DSS group, while mucosae were repaired in the AOM/DSS + Bs group. The mRNA expression levels of IL-6 and IL-17a were lower while those of IL-10 and TGF-β1 were higher, and the expression level of Ki-67 decreased while that of caspase 3 increased in the AOM/DSS + Bs group. Bs intervention could alter the structure of intestinal floras, repair the mucosal barrier, adjust immunity, and reduce the incidence of cancer in the AOM/DSS animal model.
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Affiliation(s)
- Chuancong Wu
- Department of Gastroenterology, Third Xiangya Hospital, Central South UniversityChangsha 410013, Hunan, China
| | - Mao Ouyang
- Department of Geriatrics, Third Xiangya Hospital, Central South UniversityChangsha 410013, Hunan, China
| | - Qin Guo
- Department of Gastroenterology, Third Xiangya Hospital, Central South UniversityChangsha 410013, Hunan, China
| | - Jia Jia
- Department of Gastroenterology, Third Xiangya Hospital, Central South UniversityChangsha 410013, Hunan, China
| | - Rui Liu
- Department of Gastroenterology, Third Xiangya Hospital, Central South UniversityChangsha 410013, Hunan, China
| | - Yufen Jiang
- Department of Gastroenterology, Third Xiangya Hospital, Central South UniversityChangsha 410013, Hunan, China
| | - Minghua Wu
- Cancer Research Institute, Central South UniversityChangsha 410013, Hunan, China
| | - Shourong Shen
- Department of Gastroenterology, Third Xiangya Hospital, Central South UniversityChangsha 410013, Hunan, China
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36
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Dejea CM, Fathi P, Craig JM, Boleij A, Taddese R, Geis AL, Wu X, DeStefano Shields CE, Hechenbleikner EM, Huso DL, Anders RA, Giardiello FM, Wick EC, Wang H, Wu S, Pardoll DM, Housseau F, Sears CL. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 2018; 359:592-597. [PMID: 29420293 PMCID: PMC5881113 DOI: 10.1126/science.aah3648] [Citation(s) in RCA: 747] [Impact Index Per Article: 106.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 09/28/2017] [Accepted: 12/28/2017] [Indexed: 12/23/2022]
Abstract
Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of the gut microbiome; however, the microbiota associated with precancerous lesions in hereditary CRC remains largely unknown. We studied colonic mucosa of patients with familial adenomatous polyposis (FAP), who develop benign precursor lesions (polyps) early in life. We identified patchy bacterial biofilms composed predominately of Escherichia coli and Bacteroides fragilis Genes for colibactin (clbB) and Bacteroides fragilis toxin (bft), encoding secreted oncotoxins, were highly enriched in FAP patients' colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with E. coli (expressing colibactin), and enterotoxigenic B. fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacterial strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.
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Affiliation(s)
- Christine M Dejea
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA
- Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
| | - Payam Fathi
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA
- Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
- Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - John M Craig
- Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Annemarie Boleij
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA
- Department of Pathology, Radboud University Medical Center, Postbus 9101, 6500 HB Nijmegen, Netherlands
| | - Rahwa Taddese
- Department of Pathology, Radboud University Medical Center, Postbus 9101, 6500 HB Nijmegen, Netherlands
| | - Abby L Geis
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA
- Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
| | - Xinqun Wu
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA
- Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Christina E DeStefano Shields
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA
- Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
| | | | - David L Huso
- Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, USA
| | - Robert A Anders
- Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
| | - Francis M Giardiello
- Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
- Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Elizabeth C Wick
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Hao Wang
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA
- Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
| | - Shaoguang Wu
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA
- Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Drew M Pardoll
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA
- Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
| | - Franck Housseau
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA
- Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
| | - Cynthia L Sears
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA.
- Department of Oncology, Johns Hopkins University, Baltimore, MD, USA
- Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
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Chen J, Domingue JC, Sears CL. Microbiota dysbiosis in select human cancers: Evidence of association and causality. Semin Immunol 2017; 32:25-34. [PMID: 28822617 DOI: 10.1016/j.smim.2017.08.001] [Citation(s) in RCA: 118] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 07/25/2017] [Accepted: 08/03/2017] [Indexed: 02/06/2023]
Abstract
The human microbiota is a complex ecosystem of diverse microorganisms consisting of bacteria, viruses, and fungi residing predominantly in epidermal and mucosal habitats across the body, such as skin, oral cavity, lung, intestine and vagina. These symbiotic communities in health, or dysbiotic communities in disease, display tremendous interaction with the local environment and systemic responses, playing a critical role in the host's nutrition, immunity, metabolism and diseases including cancers. While the profiling of normal microbiota in healthy populations is useful and necessary, more recent studies have focused on the microbiota associated with disease, particularly cancers. In this paper, we review current evidence on the role of the human microbiota in four cancer types (colorectal cancer, head and neck cancer, pancreatic cancer, and lung cancer) proposed as affected by both the oral and gut microbiota, and provide a perspective on current gaps in the knowledge of the microbiota and cancer.
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Affiliation(s)
- Jie Chen
- Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA
| | - Jada C Domingue
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Cynthia L Sears
- Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Oncology, Division of Tumor Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg-Kimmel Cancer Immunotherapy Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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Streptococcus gallolyticus subsp. gallolyticus promotes colorectal tumor development. PLoS Pathog 2017; 13:e1006440. [PMID: 28704539 PMCID: PMC5509344 DOI: 10.1371/journal.ppat.1006440] [Citation(s) in RCA: 146] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 05/31/2017] [Indexed: 02/07/2023] Open
Abstract
Streptococcus gallolyticus subsp. gallolyticus (Sg) has long been known to have a strong association with colorectal cancer (CRC). This knowledge has important clinical implications, and yet little is known about the role of Sg in the development of CRC. Here we demonstrate that Sg promotes human colon cancer cell proliferation in a manner that depends on cell context, bacterial growth phase and direct contact between bacteria and colon cancer cells. In addition, we observed increased level of β-catenin, c-Myc and PCNA in colon cancer cells following incubation with Sg. Knockdown or inhibition of β-catenin abolished the effect of Sg. Furthermore, mice administered with Sg had significantly more tumors, higher tumor burden and dysplasia grade, and increased cell proliferation and β-catenin staining in colonic crypts compared to mice receiving control bacteria. Finally, we showed that Sg is present in the majority of CRC patients and is preferentially associated with tumor compared to normal tissues obtained from CRC patients. These results taken together establish for the first time a tumor-promoting role of Sg that involves specific bacterial and host factors and have important clinical implications.
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Corredoira J, Grau I, Garcia-Rodriguez JF, García-País MJ, Rabuñal R, Ardanuy C, García-Garrote F, Coira A, Alonso MP, Boleij A, Pallares R. Colorectal neoplasm in cases of Clostridium septicum and Streptococcus gallolyticus subsp. gallolyticus bacteraemia. Eur J Intern Med 2017; 41:68-73. [PMID: 28236516 DOI: 10.1016/j.ejim.2017.02.009] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Revised: 02/12/2017] [Accepted: 02/14/2017] [Indexed: 01/25/2023]
Abstract
BACKGROUND Bacteremia with Clostridium septicum (CS) and Streptococcus gallolyticus subsp. gallolyticus (SGG) have both been associated with colorectal neoplasms (CRN) and colonoscopic examination is advised, however the differences and similarities in colorectal findings are not well known. METHODS This is a multicenter, comparative study of patients with CS bacteremia [44 of 664 cases (6.6%) of Clostridium spp.] and SGG bacteremia [257 of 596 cases (44.2%) of S. bovis group], carried out in three hospitals from Spain. Clinical findings related to bacteremia and associated CRN were collected. RESULTS The main sources of infection were abdominal (77.7%) for CS bacteremia and endovascular (75%) for SGG bacteremia. CS bacteremia was more often associated with malignancies, (72.6% vs. 19.4%) and neutropenia (29.5% vs. 3.1%), and was more acute, with shock at presentation (63.6% vs. 3.9%) and higher 30-day mortality (47.7% vs. 9.7%) compared to SGG (P<0.05 for all). Both, patients with CS and SGG bacteremia often had concomitant CRN (43.1% vs. 49.8%) and most of them presented as occult CRN (73.7% vs. 91.4%; P=0.02). CS cases more often had invasive carcinomas (94.7% vs. 19.5%), location of CRN in the right colon (73.7% vs. 23.4%), larger tumor size (median 7 vs. 1.5cm), and a higher overall CRN related mortality rate (68.4% vs. 7.8%) compared to SGG cases (P<0.05 for all). CONCLUSIONS Both, CS and SGG bacteremia are associated with occult CRN. CS cases more often had advanced carcinomas than SGG cases, suggesting a distinct temporal association with CRN.
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Affiliation(s)
- Juan Corredoira
- Infectious Disease Unit and Microbiology Departments, Hospital Universitario Lucus Augusti, Lugo, Spain.
| | - Imma Grau
- Infectious Disease and Microbiology Departments, Hospital Bellvitge, Ciberes, Idibell, University of Barcelona, L'Hospitalet, Barcelona, Spain.
| | | | - María Jose García-País
- Infectious Disease Unit and Microbiology Departments, Hospital Universitario Lucus Augusti, Lugo, Spain.
| | - Ramón Rabuñal
- Infectious Disease Unit and Microbiology Departments, Hospital Universitario Lucus Augusti, Lugo, Spain.
| | - Carmen Ardanuy
- Infectious Disease and Microbiology Departments, Hospital Bellvitge, Ciberes, Idibell, University of Barcelona, L'Hospitalet, Barcelona, Spain.
| | - Fernando García-Garrote
- Infectious Disease Unit and Microbiology Departments, Hospital Universitario Lucus Augusti, Lugo, Spain.
| | - Amparo Coira
- Infectious Disease Unit and Microbiology Departments, Hospital Universitario Lucus Augusti, Lugo, Spain.
| | - Maria Pilar Alonso
- Infectious Disease Unit and Microbiology Departments, Hospital Universitario Lucus Augusti, Lugo, Spain.
| | - Annemarie Boleij
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
| | - Roman Pallares
- Infectious Disease and Microbiology Departments, Hospital Bellvitge, Ciberes, Idibell, University of Barcelona, L'Hospitalet, Barcelona, Spain.
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Lv Y, Ye T, Wang HP, Zhao JY, Chen WJ, Wang X, Shen CX, Wu YB, Cai YK. Suppression of colorectal tumorigenesis by recombinant Bacteroides fragilis enterotoxin-2 in vivo. World J Gastroenterol 2017; 23:603-613. [PMID: 28216966 PMCID: PMC5292333 DOI: 10.3748/wjg.v23.i4.603] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Revised: 11/19/2016] [Accepted: 12/08/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the impact of recombinant Bacteroides fragilis enterotoxin-2 (BFT-2, or Fragilysin) on colorectal tumorigenesis in mice induced by azoxymethane/dextran sulfate sodium (AOM/DSS).
METHODS Recombinant proBFT-2 was expressed in Escherichia coli strain Rosetta (DE3) and BFT-2 was obtained and tested for its biological activity via colorectal adenocarcinoma cell strains SW-480. Seventy C57BL/6J mice were randomly divided into a blank (BC; n = 10), model (AD; n = 20), model + low-dose toxin (ADLT; n = 20, 10 μg), and a model + high-dose toxin (ADHT; n = 20, 20 μg) group. Mice weight, tumor formation and pathology were analyzed. Immunohistochemistry determined Ki-67 and Caspase-3 expression in normal and tumor tissues of colorectal mucosa.
RESULTS Recombinant BFT-2 was successfully obtained, along with its biological activity. The most obvious weight loss occurred in the AD group compared with the ADLT group (21.82 ± 0.68 vs 23.23 ± 0.91, P < 0.05) and the ADHT group (21.82 ± 0.68 vs 23.57 ± 1.06, P < 0.05). More tumors were found in the AD group than in the ADLT and ADHT groups (19.75 ± 3.30 vs 6.50 ± 1.73, P < 0.05; 19.75 ± 3.30 vs 6.00 ± 2.16, P < 0.05). Pathology showed that 12 mice had adenocarcinoma and 6 cases had adenoma in the AD group. Five mice had adenocarcinoma and 15 had adenoma in the ADLT group. Four mice had adenocarcinoma and 16 had adenoma in the ADHT group. The incidence of colorectal adenocarcinoma in both the ADHT group and the ADHT group was reduced compared to that in the AD group (P < 0.05, P < 0.05). The positive rate of Ki-67 in the ADLT group and the ADHT group was 50% and 40%, respectively, both of which were lower than that found in the AD group (94.44%, P < 0.05, P < 0.05). Caspase-3 expression in the ADLT group and the ADHT group was 45% and 55%, both of which were higher than that found in the BC group (16.67%, P < 0.05, P < 0.05).
CONCLUSION Oral administration with lower-dose biologically active recombinant BFT-2 inhibited colorectal tumorigenesis in mice.
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Structural Change in Microbiota by a Probiotic Cocktail Enhances the Gut Barrier and Reduces Cancer via TLR2 Signaling in a Rat Model of Colon Cancer. Dig Dis Sci 2016; 61:2908-2920. [PMID: 27384052 DOI: 10.1007/s10620-016-4238-7] [Citation(s) in RCA: 107] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Accepted: 06/21/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND Structural change in the gut microbiota is implicated in cancer. The beneficial modulation of the microbiota composition with probiotics and prebiotics prevents diseases. AIM We investigated the effect of oligofructose-maltodextrin-enriched Lactobacillus acidophilus, Bifidobacteria bifidum, and Bifidobacteria infantum (LBB), on the gut microbiota composition and progression of colorectal cancer. METHODS Sprague Dawley rats were acclimatized, given ampicillin (75 mg/kg), and treated as follows; GCO: normal control; GPR: LBB only; GPC: LBB+ 1,2-dimethylhydrazine dihydrochloride (DMH); and GCA: DMH only (cancer control). 16S V4 Pyrosequencing for gut microbiota analysis, tumor studies, and the expression of MUC2, ZO-1, occludin, TLR2, TLR4, caspase 3, COX-2, and β-catenin were conducted at the end of experiment. RESULTS Probiotic LBB treatment altered the gut microbiota. The relative abundance of genera Pseudomonas, Congregibacter, Clostridium, Candidactus spp., Phaeobacter, Escherichia, Helicobacter, and HTCC was decreased (P < 0.05), but the genus Lactobacillus increased (P < 0.05), in LBB treatment than in cancer control. The altered gut microbiota was associated with decreased tumor incidence (80 % in GPC vs. 100 % in GCA, P = 0.0001), tumor volume (GPC 84.23 (42.75-188.4) mm(3) vs. GCA 243 (175.5-344.5) mm(3), P < 0.0001) and tumor multiplicity/count (GPC 2.92 ± 0.26 vs. GCA 6.27 ± 0.41; P < 0.0001). The expression of MUC2, ZO-1, occludin, and TLR2 was increased, but expression of TLR4, caspase 3, Cox-2, and β-catenin was decreased by LBB treatment than in cancer control GCA (P < 0.05). CONCLUSION Administration of LBB modulates the gut microbiota and reduces colon cancer development by decreasing tumor incidence, multiplicity/count, and volume via enhanced TLR2-improved gut mucosa epithelial barrier integrity and suppression of apoptosis and inflammation.
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Wroblewski LE, Peek RM, Coburn LA. The Role of the Microbiome in Gastrointestinal Cancer. Gastroenterol Clin North Am 2016; 45:543-56. [PMID: 27546848 PMCID: PMC4994977 DOI: 10.1016/j.gtc.2016.04.010] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Humans are host to complex microbial communities previously termed normal flora and largely overlooked. However, resident microbes contribute to both health and disease. Investigators are beginning to define microbes that contribute to the development of gastrointestinal malignancies and the mechanisms by which this occurs. Resident microbes can induce inflammation, leading to cell proliferation and altered stem cell dynamics, which can lead to alterations in DNA integrity and immune regulation and promote carcinogenesis. Studies in human patients and rodent models of cancer have identified alterations in the microbiota of the stomach, esophagus, and colon that increase the risk for malignancy.
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Affiliation(s)
- Lydia E. Wroblewski
- Division of Gastroenterology, Department of Medicine; Vanderbilt University School of Medicine; Nashville, TN USA, T: 615-322-4215
| | - Richard M. Peek
- Division of Gastroenterology, Department of Medicine; Vanderbilt University School of Medicine; Nashville, TN USA, T: 615-343-1596
| | - Lori A. Coburn
- Veterans Affairs Tennessee Valley Healthcare System; Division of Gastroenterology, Department of Medicine; Vanderbilt University School of Medicine; Nashville, TN USA, T: 615-875-4222, F: 615-343-4229
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Ambalam P, Raman M, Purama RK, Doble M. Probiotics, prebiotics and colorectal cancer prevention. Best Pract Res Clin Gastroenterol 2016; 30:119-31. [PMID: 27048903 DOI: 10.1016/j.bpg.2016.02.009] [Citation(s) in RCA: 159] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 02/05/2016] [Accepted: 02/11/2016] [Indexed: 01/31/2023]
Abstract
Colorectal cancer (CRC), the third major cause of mortality among various cancer types in United States, has been increasing in developing countries due to varying diet and dietary habits and occupational hazards. Recent evidences showed that composition of gut microbiota could be associated with the development of CRC and other gut dysbiosis. Modulation of gut microbiota by probiotics and prebiotics, either alone or in combination could positively influence the cross-talk between immune system and microbiota, would be beneficial in preventing inflammation and CRC. In this review, role of probiotics and prebiotics in the prevention of CRC has been discussed. Various epidemiological and experimental studies, specifically gut microbiome research has effectively improved the understanding about the role of probiotics and microbial treatment as anticarcinogenic agents. A few human studies support the beneficial effect of probiotics and prebiotics; hence, comprehensive understanding is urgent to realize the clinical applications of probiotics and prebiotics in CRC prevention.
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Affiliation(s)
- Padma Ambalam
- Department of Biotechnology, Christ College, Rajkot, India.
| | - Maya Raman
- Bioengineering and Drug Design Lab, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering, Indian Institute of Technology, Chennai, India
| | - Ravi Kiran Purama
- School of Biotechnology, Chemical Building, East Campus, NIT Calicut, Calicut, India
| | - Mukesh Doble
- Bioengineering and Drug Design Lab, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences and Bioengineering, Indian Institute of Technology, Chennai, India
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Anti-Outer membrane protein C antibodies in colorectal neoplasia. Folia Microbiol (Praha) 2015; 61:295-9. [PMID: 26612659 DOI: 10.1007/s12223-015-0437-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Accepted: 11/20/2015] [Indexed: 12/15/2022]
Abstract
Sporadic colorectal cancer (CRC) represents an enormous problem worldwide. Large intestinal microbiota play an important role in the colorectal carcinogenesis. The aim of the study was to investigate anti-Outer membrane protein C (anti-OmpC) antibodies, aimed at porin C, which is embedded in the outer membrane of gram-negative bacteria, in patients with colorectal adenoma (CRA), CRC and controls. The study included 22 patients with CRA (11 men, 11 women, aged 26-79, mean 65 ± 12), 11 patients with CRC (9 men, 2 women, aged 50-83, mean 66 ± 11) and 45 controls, blood donors (24 men, 21 women, aged 20-58, mean 38 ± 10). Serum anti-OmpC antibodies were investigated by means of ELISA. Values of 0-20 U/mL were considered to be negative; values >25 U/mL were assessed as positive. A total of 9/11 (82 %) patients with CRC had positive anti-OmpC antibodies. Anti-OmpC antibodies were negative or grey-zone in 37/45 (82 %) controls. Serum anti-OmpC were found to be significantly higher in patients with CRC (median 42.4, interquartile range (IQR) 22.2) compared to controls (median 18.3, IQR 12.4), p < 0.001. No statistically significant difference in anti-OmpC was found between controls (median 18.3, IQR 12.4) and CRA patients (median 17.7, IQR 16.5), p = 0.326. Anti-OmpC were significantly higher in patients with CRC (median 42.4, IQR 22.2) compared to patients with CRA (median 17.7, IQR 16.5), p = 0.011. Positivity of anti-OmpC antibodies was found in patients with CRC, which supports the contribution of gram-negative large intestinal microbiota to the pathogenesis of CRC.
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Rosadi F, Fiorentini C, Fabbri A. Bacterial protein toxins in human cancers. Pathog Dis 2015; 74:ftv105. [DOI: 10.1093/femspd/ftv105] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2015] [Indexed: 12/16/2022] Open
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Russo G, Patrignani A, Poveda L, Hoehn F, Scholtka B, Schlapbach R, Garvin AM. Highly sensitive, non-invasive detection of colorectal cancer mutations using single molecule, third generation sequencing. Appl Transl Genom 2015; 7:32-9. [PMID: 27054083 PMCID: PMC4803778 DOI: 10.1016/j.atg.2015.08.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Revised: 07/29/2015] [Accepted: 08/03/2015] [Indexed: 12/18/2022]
Abstract
Colorectal cancer (CRC) represents one of the most prevalent and lethal malignant neoplasms and every individual of age 50 and above should undergo regular CRC screening. Currently, the most effective preventive screening procedure to detect adenomatous polyps, the precursors to CRC, is colonoscopy. Since every colorectal cancer starts as a polyp, detecting all polyps and removing them is crucial. By exactly doing that, colonoscopy reduces CRC incidence by 80%, however it is an invasive procedure that might have unpleasant and, in rare occasions, dangerous side effects. Despite numerous efforts over the past two decades, a non-invasive screening method for the general population with detection rates for adenomas and CRC similar to that of colonoscopy has not yet been established. Recent advances in next generation sequencing technologies have yet to be successfully applied to this problem, because the detection of rare mutations has been hindered by the systematic biases due to sequencing context and the base calling quality of NGS. We present the first study that applies the high read accuracy and depth of single molecule, real time, circular consensus sequencing (SMRT-CCS) to the detection of mutations in stool DNA in order to provide a non-invasive, sensitive and accurate test for CRC. In stool DNA isolated from patients diagnosed with adenocarcinoma, we are able to detect mutations at frequencies below 0.5% with no false positives. This approach establishes a foundation for a non-invasive, highly sensitive assay to screen the population for CRC and the early stage adenomas that lead to CRC.
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Affiliation(s)
- Giancarlo Russo
- Functional Genomics Center Zurich, ETH/University of Zurich, Zurich, Switzerland
| | - Andrea Patrignani
- Functional Genomics Center Zurich, ETH/University of Zurich, Zurich, Switzerland
| | - Lucy Poveda
- Functional Genomics Center Zurich, ETH/University of Zurich, Zurich, Switzerland
| | | | - Bettina Scholtka
- Department of Nutritional Toxicology, Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
| | - Ralph Schlapbach
- Functional Genomics Center Zurich, ETH/University of Zurich, Zurich, Switzerland
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Kostic AD, Chun E, Meyerson M, Garrett WS. Microbes and inflammation in colorectal cancer. Cancer Immunol Res 2015; 1:150-7. [PMID: 24777677 DOI: 10.1158/2326-6066.cir-13-0101] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Over the past decade, there has been a renaissance in research on physiologic interactions between humans and their resident microbiota, the vast numbers of bacteria, fungi, and viruses that live within and on the body. The burgeoning interest in what constitutes the human microbiome has also focused on the contribution of microbes to carcinogenesis. Given the microbiomes of malignancies arising at mucosal sites, the microbiota may prove as influential as stromal cells and immune cells in the tumor microenvironment. Herein, we focus on the interconnections of microbes and inflammation in colorectal carcinogenesis.
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Affiliation(s)
- Aleksandar D Kostic
- Authors' Affiliations: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
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Banerjee J, Mishra N, Dhas Y. Metagenomics: A new horizon in cancer research. Meta Gene 2015; 5:84-9. [PMID: 26110115 PMCID: PMC4477109 DOI: 10.1016/j.mgene.2015.05.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Revised: 05/21/2015] [Accepted: 05/26/2015] [Indexed: 12/28/2022] Open
Abstract
Metagenomics has broadened the scope of targeting microbes responsible for inducing various types of cancers. About 16.1% of cancers are associated with microbial infection. Metagenomics is an equitable way of identifying and studying micro-organisms within their habitat. In cancer research, this approach has revolutionized the way of identifying, analyzing and targeting the microbial diversity present in the tissue specimens of cancer patients. The genomic analyses of these micro-organisms through next generation sequencing techniques invariably facilitate in recognizing the microbial population in biopsies and their evolutionary relationships with each other. In this review an attempt has been made to generate current metagenomic view on cancer microbiota. Different types of micro-organisms have been found to be linked to various types of cancers, thus, contributing significantly in understanding the disease at molecular level.
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Affiliation(s)
- Joyita Banerjee
- Symbiosis School of Biomedical Sciences, Symbiosis International University, Pune 412115, India
| | - Neetu Mishra
- Symbiosis School of Biomedical Sciences, Symbiosis International University, Pune 412115, India
| | - Yogita Dhas
- Symbiosis School of Biomedical Sciences, Symbiosis International University, Pune 412115, India
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Complete Genome Sequence of an Enterotoxigenic Bacteroides fragilis Clinical Isolate. GENOME ANNOUNCEMENTS 2015; 3:3/3/e00450-15. [PMID: 25953165 PMCID: PMC4424316 DOI: 10.1128/genomea.00450-15] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Here we present the complete genome sequence of Bacteroides fragilis isolate BOB25. It is an enterotoxigenic isolate that was obtained from a stool sample of a patient with dysbiosis.
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Development of miniature mass spectrometry systems for bioanalysis outside the conventional laboratories. Bioanalysis 2015; 6:1497-508. [PMID: 25046050 DOI: 10.4155/bio.14.100] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Mass spectrometry (MS) is known for highly specific and sensitive analysis. The general applicability of this technique makes it a good candidate for biological applications over a much broader range than is now the case. The limiting factors preventing MS from being applied at the biologist's bench or in a physician's office are identified as the large size of the systems, as well as the complicated analytical procedures required. An approach for developing miniature MS analysis systems with simplified operational procedures is described and the associated technical developments are discussed.
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