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Sun W, Ma S, Meng D, Wang C, Zhang J. Advances in research on the intestinal microbiota in the mechanism and prevention of colorectal cancer (Review). Mol Med Rep 2025; 31:133. [PMID: 40116116 PMCID: PMC11948985 DOI: 10.3892/mmr.2025.13498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 02/19/2025] [Indexed: 03/23/2025] Open
Abstract
The intestinal microbiota represents a diverse population that serves a key role in colorectal cancer (CRC) and its treatment outcomes. Advancements in sequencing have revealed notable shifts in microbial composition and diversity among individuals with CRC. Concurrently, animal models have elucidated the involvement of specific microbes such as Lactobacillus fragilis, Escherichia coli and Fusobacterium nucleatum in the progression of CRC. The present review aimed to highlight contributions of intestinal microbiota to the pathogenesis of CRC, the effects of traditional treatments on intestinal microbiota and the potential for microbiota modulation as a therapeutic strategy for CRC.
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Affiliation(s)
- Weitong Sun
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154000, P.R. China
| | - Shize Ma
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154000, P.R. China
| | - Dongdong Meng
- Department of Medical Services, Xuzhou Morning Star Women's and Children's Hospital, Xuzhou, Jiangsu 221000, P.R. China
| | - Chaoxing Wang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154000, P.R. China
| | - Jinbo Zhang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang 154000, P.R. China
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2
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Mascaretti F, Haider S, Amoroso C, Caprioli F, Ramai D, Ghidini M. Role of the Microbiome in the Diagnosis and Management of Gastroesophageal Cancers. J Gastrointest Cancer 2024; 55:662-678. [PMID: 38411876 DOI: 10.1007/s12029-024-01021-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2024] [Indexed: 02/28/2024]
Abstract
PURPOSE Stomach and esophageal cancers are among the highest mortality from cancers worldwide. Microbiota has an interplaying role within the human gastrointestinal (GI) tract. Dysbiosis occurs when a disruption of the balance between the microbiota and the host happens. With this narrative review, we discuss the main alterations in the microbiome of gastroesophageal cancer, revealing its potential role in the pathogenesis, early detection, and treatment. RESULTS Helicobacter pylori plays a major role the development of a cascade of preneoplastic conditions ranging from atrophic gastritis to metaplasia and dysplasia, ultimately culminating in gastric cancer, while other pathogenic agents are Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli, and Lactobacillus. Campylobacter species (spp.)'s role in the progression of esophageal adenocarcinoma may parallel that of Helicobacter pylori in the context of gastric cancer, with other esophageal carcinogenic agents being Escherichia coli, Bacteroides fragilis, and Fusobacterium nucleatum. Moreover, gut microbiome could significantly alter the outcomes of chemotherapy and immunotherapy. The gut microbiome can be modulated through interventions such as antibiotics, probiotics, or prebiotics intake. Fecal microbiota transplantation has emerged as a therapeutic strategy as well. CONCLUSIONS Nowadays, it is widely accepted that changes in the normal gut microbiome causing dysbiosis and immune dysregulation play a role gastroesophageal cancer. Different interventions, including probiotics and prebiotics intake are being developed to improve therapeutic outcomes and mitigate toxicities associated with anticancer treatment. Further studies are required in order to introduce the microbiome among the available tools of precision medicine in the field of anticancer treatment.
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Affiliation(s)
- Federica Mascaretti
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Salman Haider
- Department of Internal Medicine, Brooklyn Hospital Center, Brooklyn, New York, NY, USA
| | - Chiara Amoroso
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Flavio Caprioli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Daryl Ramai
- Division of Gastroenterology and Hepatology, University of Utah Health, Salt Lake City, UT, USA
| | - Michele Ghidini
- Medical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122, Via Sforza 28, Milan, Italy.
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3
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Shang F, Jiang X, Wang H, Guo S, Kang S, Xu B, Wang X, Chen S, Li N, Liu B, Zhao Z. Bifidobacterium longum suppresses colorectal cancer through the modulation of intestinal microbes and immune function. Front Microbiol 2024; 15:1327464. [PMID: 38585690 PMCID: PMC10995357 DOI: 10.3389/fmicb.2024.1327464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 02/12/2024] [Indexed: 04/09/2024] Open
Abstract
Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function.
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Affiliation(s)
- Fangjian Shang
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xia Jiang
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Haobo Wang
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shang Guo
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shuo Kang
- Medical Insurance Office, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Bin Xu
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xin Wang
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shihao Chen
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Ning Li
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Bo Liu
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zengren Zhao
- Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China
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4
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Chen Z, Guan D, Wang Z, Li X, Dong S, Huang J, Zhou W. Microbiota in cancer: molecular mechanisms and therapeutic interventions. MedComm (Beijing) 2023; 4:e417. [PMID: 37937304 PMCID: PMC10626288 DOI: 10.1002/mco2.417] [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: 06/27/2023] [Revised: 10/04/2023] [Accepted: 10/12/2023] [Indexed: 11/09/2023] Open
Abstract
The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, and metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant cell signaling pathways, influencing tumor cell metabolism, promoting revascularization, and remodeling the tumor immune microenvironment. These microbiota-mediated effects significantly impact overall survival and the recurrence of tumors after surgery by affecting the efficacy of chemoradiotherapy. Moreover, leveraging the microbiota for the development of biovectors, probiotics, prebiotics, and synbiotics, in addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, and fecal microbiota transplantation, offers promising alternatives for cancer treatment. Nonetheless, due to the extensive and diverse nature of the microbiota, along with tumor heterogeneity, the molecular mechanisms underlying the role of microbiota in cancer remain a subject of intense debate. In this context, we refocus on various cancers, delving into the molecular signaling pathways associated with the microbiota and its derivatives, the reshaping of the tumor microenvironmental matrix, and the impact on tolerance to tumor treatments such as chemotherapy and radiotherapy. This exploration aims to shed light on novel perspectives and potential applications in the field.
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Affiliation(s)
- Zhou Chen
- The First Clinical Medical CollegeLanzhou UniversityLanzhouGansuChina
- The First Hospital of Lanzhou UniversityLanzhouGansuChina
| | - Defeng Guan
- The First Clinical Medical CollegeLanzhou UniversityLanzhouGansuChina
- The First Hospital of Lanzhou UniversityLanzhouGansuChina
| | - Zhengfeng Wang
- The First Clinical Medical CollegeLanzhou UniversityLanzhouGansuChina
- The First Hospital of Lanzhou UniversityLanzhouGansuChina
| | - Xin Li
- The Second Clinical Medical CollegeLanzhou UniversityLanzhouGansuChina
- The Department of General SurgeryLanzhou University Second HospitalLanzhouGansuChina
| | - Shi Dong
- The Second Clinical Medical CollegeLanzhou UniversityLanzhouGansuChina
- The Department of General SurgeryLanzhou University Second HospitalLanzhouGansuChina
| | - Junjun Huang
- The First Hospital of Lanzhou UniversityLanzhouGansuChina
| | - Wence Zhou
- The First Clinical Medical CollegeLanzhou UniversityLanzhouGansuChina
- The Department of General SurgeryLanzhou University Second HospitalLanzhouGansuChina
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Barreira MA, Campelo MWS, da Silva Martins Rebouças C, Duarte ASG, Barbosa MLL, da Cruz Fonseca SG, Queiroz RR, Holanda ÉU, de Vasconcelos ABA, de Sousa Araújo VJG, Diniz GM, Oriá RB, de Vasconcelos PRL. Pterostilbene and Probiotic Complex in Chemoprevention of Putative Precursor Lesions for Colorectal Cancer in an Experimental Model of Intestinal Carcinogenesis with 1,2-Dimethylhydrazine. Cancers (Basel) 2023; 15:2401. [PMID: 37190329 PMCID: PMC10136993 DOI: 10.3390/cancers15082401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 03/28/2023] [Accepted: 04/12/2023] [Indexed: 05/17/2023] Open
Abstract
Dietary supplementation with pterostilbene (PS) and/or a probiotic (PRO) may ameliorate the intestinal microbiota in disease conditions. This study aims to evaluate PS and PRO for the chemoprevention of putative precursor lesions for colorectal cancer (CRC) in an experimental model of intestinal carcinogenesis with 1,2-dimethylhydrazine (1,2-DMH). Sixty male Wistar rats were equally divided into five groups: Sham, 1,2-DMH, 1,2-DMH + PS, 1,2-DMH + PRO, and 1,2-DMH + PS + PRO. PRO (5 × 107/mL) was offered in water, and PS (300 ppm) was provided in the diet ad libitum. 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. PRO alone and PRO combined with PS were the best intervention strategies to improve experimental 1,2-DMH-induced CRC regarding several parameters of carcinogenesis. Our findings may contribute to the development of novel preventive strategies for CRC and may help to identify novel modulators of colon carcinogenesis.
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Affiliation(s)
- Márcio Alencar Barreira
- Walter Cantídio University Hospital, Federal University of Ceará, Fortaleza 60430-140, CE, Brazil
| | - Márcio Wilker Soares Campelo
- Department of Surgery, School of Medicine, Federal University of Ceará, Fortaleza 60430-140, CE, Brazil
- School of Medicine, Christus University Center (UNICHRISTUS), Fortaleza 60192-345, CE, Brazil
| | - Conceição da Silva Martins Rebouças
- Laboratory of Tissue Healing, Ontogeny, and Nutrition, Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza 60430-170, CE, Brazil
| | - Antoniella Souza Gomes Duarte
- Laboratory of Tissue Healing, Ontogeny, and Nutrition, Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza 60430-170, CE, Brazil
| | - Maria Lucianny Lima Barbosa
- Laboratory of Tissue Healing, Ontogeny, and Nutrition, Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza 60430-170, CE, Brazil
| | | | | | - Érica Uchoa Holanda
- School of Medicine, Christus University Center (UNICHRISTUS), Fortaleza 60192-345, CE, Brazil
| | | | | | - Gabriel Maia Diniz
- School of Medicine, Christus University Center (UNICHRISTUS), Fortaleza 60192-345, CE, Brazil
| | - Reinaldo Barreto Oriá
- Laboratory of Tissue Healing, Ontogeny, and Nutrition, Department of Morphology, School of Medicine, Federal University of Ceará, Fortaleza 60430-170, CE, Brazil
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de Oliveira CS, Baptistella MM, Siqueira AP, Carvalho MO, Ramos LF, Souto BS, de Almeida LA, Dos Santos EG, Novaes RD, Nogueira ESC, de Oliveira PF. Combination of vitamin D and probiotics inhibits chemically induced colorectal carcinogenesis in Wistar rats. Life Sci 2023; 322:121617. [PMID: 37003542 DOI: 10.1016/j.lfs.2023.121617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 03/10/2023] [Accepted: 03/20/2023] [Indexed: 04/03/2023]
Abstract
The modulation of inflammatory elements, cell differentiation and proliferation by vitamin D and the role of probiotics in the intestinal microbiota and immunogenic response have sparked interest in the application of both in chemotherapeutics and chemoprevention of colorectal tumors. AIMS The present study aimed to investigate the effects of isolated and/or combined treatment of vitamin D3 and probiotics on colorectal carcinogenesis. MAIN METHODS Pre-neoplastic lesions were induced with 1,2-dimethylhydrazine in the colon of Wistar rats, which were treated with probiotics and/or vitamin D in three different approaches (simultaneous, pre-, and post-treatment). We investigated the frequency of aberrant crypt foci (ACF) and aberrant crypt (AC) in the distal colon, fecal microbiome composition, gene and protein expression through immunohistochemical and RT-PCR assays, and general toxicity through water consumption and weight gain monitoring. KEY FINDINGS Results confirm the systemic safety of treatments, and show a protective effect of vitamin D and probiotics in all approaches studied, as well as in combined treatments, with predominance of different bacterial phyla compared to controls. Treated groups show different levels of Nrf2, GST, COX2, iNOS, β-catenin and PCNA expression. SIGNIFICANCE These experimental conditions explore the combination of vitamin D and probiotics supplementation at low doses over pathways involved in distinct stages of colorectal carcinogenesis, with results supporting its application in prevention and long-term strategies.
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Affiliation(s)
- Carolina S de Oliveira
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil; Postgraduate Program in Biosciences Applied to Health, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Mariane M Baptistella
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil; Postgraduate Program in Biosciences Applied to Health, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Alexia P Siqueira
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Michele O Carvalho
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil; Postgraduate Program in Nutrition and Longevity, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Luiz Fernando Ramos
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Bianca S Souto
- Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Leonardo A de Almeida
- Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Elda G Dos Santos
- Postgraduate Program in Biosciences Applied to Health, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Rômulo D Novaes
- Department of Structural Biology, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Ester S C Nogueira
- Animal Integrative Biology Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Pollyanna F de Oliveira
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil; Postgraduate Program in Nutrition and Longevity, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil; Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil.
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7
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Bai J, Wang S, Xu F, Dong M, Wang J, Sun X, Xiao G. L. reuteri JMR-01 adjuvant 12C 6+ irradiation exerts anti-colon carcinoma effects by modulating the gut microbiota in mice. Int J Radiat Biol 2023; 99:779-790. [PMID: 36731457 DOI: 10.1080/09553002.2023.2142979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Probiotics such as Lactobacillus could modulate the intestinal microbiota and have been considered as an effective strategy for ameliorating colon carcinoma. Nevertheless, its efficiency remains the biggest challenge. METHODS We investigated the therapeutic efficacy of Lactobacillus reuteri JMR-01 adjuvant 12C6+ irradiation on CT-26 syngeneic mouse models. Meanwhile, intestinal flora and innate immunity were examined to outline mechanisms. RESULTS Anti-proliferation effect of live probiotic combined with inactivated probiotic JMR-01 (LP + IP) on CT-26 reached a maximum of 39.55% among other experiment groups at 24 h when the ratio of cell to CFU was 1:1 in vitro. These activities have been fully validated in vivo, tumor-bearing mice treated by 12C6+ irradiation combining with living and inactivated probiotics JMR-01 (IR + LP + IP) for 50-day held the highest survival rate (71.4%) and complete remission rate (14.3%). We also demonstrated significant fluctuation in gut microbiota, including the decreased abundance of Bacteroides fragilis and Clostridium perfringens related to tumorigenesis and development, and the increased abundance of Lactobacillus and Bifidobacterium closely associated with health restoration in fecal of mice treated with JMR-01 LP + IP adjuvant 12C6+ irradiation (IR + LP + IP). Similarly, the decreasing nitroreductase activities and increasing short chain fatty acids (SCFAs) concentrations were observed in IR + LP + IP group compared with tumor control group, which further confirmed the changes of gut microbiota. Additionally, we found that the strongest stimulation index of splenocyte (2.47) and the phagocytosis index peritoneal macrophage (3.68) were achieved by LP + IP compared with single live JMR-01 (LP) and inactivated JMR-01 (IP). CONCLUSIONS JMR-01 LP + IP adjuvant 12C6+ irradiation could mitigate cancer progression by modulating innate immunity as well as intestinal flora.
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Affiliation(s)
- Jin Bai
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PR China.,College of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, PR China
| | - Shuyang Wang
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PR China.,College of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, PR China.,Institute of Biology, Gansu Academy of Sciences, Lanzhou, PR China
| | - Fuqiang Xu
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PR China.,College of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, PR China
| | - Miaoyin Dong
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PR China
| | - Junkai Wang
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PR China
| | - Xisi Sun
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PR China.,College of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, PR China
| | - Guoqing Xiao
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PR China.,College of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing, PR China
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8
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Nami Y, Hejazi S, Geranmayeh MH, Shahgolzari M, Yari Khosroushahi A. Probiotic immunonutrition impacts on colon cancer immunotherapy and prevention. Eur J Cancer Prev 2023; 32:30-47. [PMID: 36134612 DOI: 10.1097/cej.0000000000000738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The important role of the immune system in treating cancer has attracted the attention of researchers to the emergence of oncology research. Immunotherapy has shown that the immune system is important in the fight against cancer. The challenge has led researchers to analyze the impact of immunotherapy on improving the status of the immune system, modifying the resulting safety response, reducing toxicity, and improving the results. This study aimed to discuss the potential mechanisms of probiotics in preventing colon cancer. The mechanisms include the change in intestinal microbiota, the metabolic activity of microbiota, the binding and degradation of the carcinogenic compounds present in the lumen of the intestine, the production of compounds with anticancer activity, immune system modification, intestinal dysfunction, changes in host physiology, and inhibition of cell proliferation and induction of apoptosis in cancerous cells. By contrast, very few reports have shown the harmful effects of oral probiotic supplements. According to available evidence, further studies on probiotics are needed, especially in identifying bacterial species with anticancer potential, studying the survival of the strains after passing the digestive tract, reviewing potential side effects in people with a weak immune system, and ultimately consuming and repeating its use. This study emphasizes that the nutritional formula can modulate inflammatory and immune responses in cancer patients. This effect reduces acute toxicity, although the pathways and measurement of this immune response are unclear. Nutrition safety is an emerging field in oncology, and further research is required.
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Affiliation(s)
- Yousef Nami
- Department of Food Biotechnology, Branch for Northwest & West Region, Agricultural Biotechnology Research Institute of Iran, Agricultural Research, Education and Extension Organization (AREEO)
| | - Salva Hejazi
- Department of Medicine, Student Research Committee, Tabriz University of Medical Sciences
| | - Mohammad Hossein Geranmayeh
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
| | - Mehdi Shahgolzari
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
- Biotechnology Research Center, Tabriz University of Medical Sciences
| | - Ahmad Yari Khosroushahi
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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9
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Singh S, Singh M, Gaur S. Probiotics as multifaceted oral vaccines against colon cancer: A review. Front Immunol 2022; 13:1002674. [PMID: 36263037 PMCID: PMC9573965 DOI: 10.3389/fimmu.2022.1002674] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 09/01/2022] [Indexed: 11/13/2022] Open
Abstract
Probiotics are known as the live microorganisms that, upon adequate administration, elicit a health beneficial response inside the host. The probiotics are known as immunomodulators and exhibit anti-tumor properties. Advanced research has explored the potential use of probiotics as the oral vaccines without the latent risks of pathogenicity. Probiotic-based oral vaccines are known to induce mucosal immunity that prevents the host from several enteric infections. Probiotic bacteria have the ability to produce metabolites in the form of anti-inflammatory cytokines, which play an important role in the prevention of carcinogenesis and in the activation of the phagocytes that eliminate the preliminary stage cancer cells. This review discusses the advantages and disadvantages of using the oral probiotic vaccines as well as the mechanism of action of probiotics in colon cancer therapy. This review also employs the use of “PROBIO” database for selecting certain probiotics with immunomodulatory properties. Furthermore, the use of several probiotic bacteria as anti-colon cancer adjuvants has also been discussed in detail. Because the current studies and trials are more focused on using the attenuated pathogens instead of using the probiotic-based vaccines, future studies must involve the advanced research in exploiting the potential of several probiotic strains as adjuvants in cancer therapies.
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Affiliation(s)
- Shubhi Singh
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
| | - Manisha Singh
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Smriti Gaur
- Department of Biotechnology, Jaypee Institute of Information Technology, Noida, India
- *Correspondence: Smriti Gaur,
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10
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Role of a mixed probiotic product, VSL#3, in the prevention and treatment of colorectal cancer. Eur J Pharmacol 2022; 930:175152. [PMID: 35835181 DOI: 10.1016/j.ejphar.2022.175152] [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: 05/19/2022] [Revised: 07/03/2022] [Accepted: 07/07/2022] [Indexed: 12/09/2022]
Abstract
Colorectal cancer (CRC) is a multifactorial disease. The incidence of this type of cancer in younger patients has increased in recent years, and more strategies are needed to prevent and delay the progression of CRC. Probiotics play an adjunctive role in the prevention and treatment of CRC and can not only prevent the onset and delay the progression of disease but also reduce the side effects after the application of anti-cancer drugs. The anti-cancer effect of individual probiotics has been extensively studied, and the exact curative effect of various probiotics has been found, but the anti-cancer effect of mixed probiotics is still not well summarized. In this review, we discuss the positive effects of mixed probiotics on CRC and the related mechanisms of action, especially VSL#3 (VSL Pharmaceuticals, Inc., Gaithersburg, MD, USA), thus providing new ideas for the treatment of CRC. Moreover, we suggest the need to search for more therapeutic possibilities, especially via the research and application of synbiotics and postbiotics.
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11
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Patra S, Sahu N, Saxena S, Pradhan B, Nayak SK, Roychowdhury A. Effects of Probiotics at the Interface of Metabolism and Immunity to Prevent Colorectal Cancer-Associated Gut Inflammation: A Systematic Network and Meta-Analysis With Molecular Docking Studies. Front Microbiol 2022; 13:878297. [PMID: 35711771 PMCID: PMC9195627 DOI: 10.3389/fmicb.2022.878297] [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: 02/18/2022] [Accepted: 04/19/2022] [Indexed: 11/13/2022] Open
Abstract
Background Dysbiosis/imbalance in the gut microbial composition triggers chronic inflammation and promotes colorectal cancer (CRC). Modulation of the gut microbiome by the administration of probiotics is a promising strategy to reduce carcinogenic inflammation. However, the mechanism remains unclear. Methods In this study, we presented a systematic network, meta-analysis, and molecular docking studies to determine the plausible mechanism of probiotic intervention in diminishing CRC-causing inflammations. Results We selected 77 clinical, preclinical, in vitro, and in vivo articles (PRISMA guidelines) and identified 36 probiotics and 135 training genes connected to patients with CRC with probiotic application. The meta-analysis rationalizes the application of probiotics in the prevention and treatment of CRC. An association network is generated with 540 nodes and 1,423 edges. MCODE cluster analysis identifies 43 densely interconnected modules from the network. Gene ontology (GO) and pathway enrichment analysis of the top scoring and functionally significant modules reveal stress-induced metabolic pathways (JNK, MAPK), immunomodulatory pathways, intrinsic apoptotic pathways, and autophagy as contributors for CRC where probiotics could offer major benefits. Based on the enrichment analyses, 23 CRC-associated proteins and 7 probiotic-derived bacteriocins were selected for molecular docking studies. Results indicate that the key CRC-associated proteins (e.g., COX-2, CASP9, PI3K, and IL18R) significantly interact with the probiotic-derived bacteriocins (e.g., plantaricin JLA-9, lactococcin A, and lactococcin mmfii). Finally, a model for probiotic intervention to reduce CRC-associated inflammation has been proposed. Conclusion Probiotics and/or probiotic-derived bacteriocins could directly interact with CRC-promoting COX2. They could modulate inflammatory NLRP3 and NFkB pathways to reduce CRC-associated inflammation. Probiotics could also activate autophagy and apoptosis by regulating PI3K/AKT and caspase pathways in CRC. In summary, the potential mechanisms of probiotic-mediated CRC prevention include multiple signaling cascades, yet pathways related to metabolism and immunity are the crucial ones.
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Affiliation(s)
- Sinjini Patra
- Biochemistry and Cell Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha, India
| | - Nilanjan Sahu
- National Institute of Science Education and Research (NISER) Bhubaneswar, Homi Bhabha National Institute (HBNI), Odisha, India
| | - Shivam Saxena
- Biochemistry and Cell Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha, India
| | - Biswaranjan Pradhan
- S. K. Dash Center of Excellence of Biosciences and Engineering & Technology (SKBET), Indian Institute of Technology Bhubaneswar, Odisha, India
| | - Saroj Kumar Nayak
- S. K. Dash Center of Excellence of Biosciences and Engineering & Technology (SKBET), Indian Institute of Technology Bhubaneswar, Odisha, India
| | - Anasuya Roychowdhury
- Biochemistry and Cell Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha, India
- *Correspondence: Anasuya Roychowdhury /0000-0003-3735-3021
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12
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Zeng X, Jia H, Shi Y, Chen K, Wang Z, Gao Z, Yuan Y, Yue T. Lactobacillus kefiranofaciens JKSP109 and Saccharomyces cerevisiae JKSP39 isolated from Tibetan kefir grain co-alleviated AOM/DSS induced inflammation and colorectal carcinogenesis. Food Funct 2022; 13:6947-6961. [PMID: 35575226 DOI: 10.1039/d1fo02939h] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
This study aimed to investigate the alleviative effects of Lactobacillus kefiranofaciens JKSP109 (LK) and Saccharomyces cerevisiae JKSP39 (SC) isolated from Tibetan kefir grain on colon inflammation and colorectal carcinogenesis. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to establish a mouse model of colorectal cancer (CRC). The treatment group mice were administered with LK, SC, or the combination of LK and SC for five days per week from the day of receiving AOM. The composition of the gut microbiota was assessed using internal transcribed spacer 2 and 16S rRNA gene high-throughput sequencing. Furthermore, the biomarkers associated with gut barrier integrity, inflammation, regulators of cell proliferation, and apoptosis were evaluated. The results showed that the administration of LK, SC, and their combination increased the body weights and decreased the disease activity index (DAI) score and tumor multiplicity. As compared to the CRC model group, the three treatment groups positively regulated the gut microbiota. Meanwhile, the three treatments also enhanced the gut barrier, decreased the expression of proinflammatory cytokines and oncocyte proliferation indicators, and increased the expression of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive tumor epithelial cells and content of short chain fatty acids in fecal samples. All these results indicated that the LK and SC alleviated the inflammation and colorectal carcinogenesis in AOM/DSS-induced CRC mouse models, and the majority of tested indexes in the combination group were superior to single strain groups.
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Affiliation(s)
- Xuejun Zeng
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Hang Jia
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Yiheng Shi
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Ke Chen
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Zhouli Wang
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Zhenpeng Gao
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Yahong Yuan
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Tianli Yue
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China.,College of Food Science and Technology, Northwest University, Xi'an, 710069, China
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13
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Paul B, Gaonkar RH, Dutta D, Dasi R, Mukherjee B, Ganguly S, Das SK. Inhibitory potential of iRGD peptide-conjugated garcinol-loaded biodegradable nanoparticles in rat colorectal carcinoma. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2022; 134:112714. [DOI: 10.1016/j.msec.2022.112714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 01/18/2022] [Accepted: 02/09/2022] [Indexed: 10/19/2022]
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14
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Chen J, Chen X, Ho CL. Recent Development of Probiotic Bifidobacteria for Treating Human Diseases. Front Bioeng Biotechnol 2022; 9:770248. [PMID: 35004640 PMCID: PMC8727868 DOI: 10.3389/fbioe.2021.770248] [Citation(s) in RCA: 91] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022] Open
Abstract
Bifidobacterium is a non-spore-forming, Gram-positive, anaerobic probiotic actinobacterium and commonly found in the gut of infants and the uterine region of pregnant mothers. Like all probiotics, Bifidobacteria confer health benefits on the host when administered in adequate amounts, showing multifaceted probiotic effects. Examples include B. bifidum, B. breve, and B. longum, common Bifidobacterium strains employed to prevent and treat gastrointestinal disorders, including intestinal infections and cancers. Herein, we review the latest development in probiotic Bifidobacteria research, including studies on the therapeutic impact of Bifidobacterial species on human health and recent efforts in engineering Bifidobacterium. This review article would provide readers with a wholesome understanding of Bifidobacteria and its potentials to improve human health.
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Affiliation(s)
- Jun Chen
- Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, China
| | - Xinyi Chen
- Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, China
| | - Chun Loong Ho
- Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, China
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15
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Zeng X, Jia H, Zhang X, Wang X, Wang Z, Gao Z, Yuan Y, Yue T. Supplementation of kefir ameliorates azoxymethane/dextran sulfate sodium induced colorectal cancer by modulating the gut microbiota. Food Funct 2021; 12:11641-11655. [PMID: 34724014 DOI: 10.1039/d1fo01729b] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The aim of this study was to investigate the efficacy of kefir on colorectal cancer (CRC) via regulating the microbiota structure in the colon using the azoxymethane/dextran sulfate sodium (AOM/DSS) induced CRC mouse model. Mice in the treatment group were orally administered with milk or kefir. The gut microbiota composition was assessed by internally transcribed spacer 2 (ITS2) and 16S rRNA high-throughput sequencing. Furthermore, the biomarkers associated with the gut barrier, inflammation, and cell proliferation regulators were evaluated. The results indicated that the size and the amount of tumor were decreased and the immunity regulators (TNF-α, IL-6, and IL-17a) and oncocyte proliferation indicator (Ki67, NF-κB, and β-catenin) were all decreased. Increased short chain fatty acids (SCFAs) lowered the pH in the colon and helped enhance the intestinal barrier. The Firmicutes/Bacteroidetes ratio and Ascomycota/Basidiomycota ratio were decreased at the phylum level; the relative abundance of probiotics was increased and the pathogenic bacterium (Clostridium sensu stricto, Aspergillus and Talaromyces) were decreased after supplementation of kefir. Consequently, kefir could regulate the gut microbiota composition and ameliorate AOM/DSS induced colorectal cancer.
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Affiliation(s)
- Xuejun Zeng
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Hang Jia
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Xiao Zhang
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Xin Wang
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Zhouli Wang
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Zhenpeng Gao
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Yahong Yuan
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China
| | - Tianli Yue
- College of Food Science and Engineering, Northwest A & F University, Yangling, 712100, China. .,Laboratory of Quality & Safety Risk Assessment for Agri-products (Yangling), Ministry of Agriculture, Yangling, 712100, China.,College of Food Science and Technology, Northwest University, Xi'an, 710069, China
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16
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Benito I, Encío IJ, Milagro FI, Alfaro M, Martínez-Peñuela A, Barajas M, Marzo F. Microencapsulated Bifidobacterium bifidum and Lactobacillus gasseri in Combination with Quercetin Inhibit Colorectal Cancer Development in Apc Min/+ Mice. Int J Mol Sci 2021; 22:4906. [PMID: 34063173 PMCID: PMC8124226 DOI: 10.3390/ijms22094906] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/28/2021] [Accepted: 05/01/2021] [Indexed: 12/12/2022] Open
Abstract
Recent studies have suggested that flavonoids such as quercetin and probiotics such as Bifidobacterium bifidum (Bf) and Lactobacillus gasseri (Lg) could play a relevant role in inhibiting colon cancer cell growth. Our study investigated the role of dietary supplementation with microencapsulated probiotics (Bf and Lg) along with quercetin in the development of mouse colorectal cancer (CRC). Methods: Adenomatous polyposis coli/multiple intestinal neoplasia (ApcMin/+) mice were fed a standard diet or the same diet supplemented with microencapsulated probiotics (Bf and Lg strains, 107 CFU/100 g food) or both probiotics strains plus microencapsulated quercetin (15 mg/100 g food) for 73 days. Changes in body and organ weights, energy metabolism, intestinal microbiota, and colon tissue were determined. The expression of genes related to the Wnt pathway was also analyzed in colon samples. Results: Dietary supplementation with microencapsulated probiotics or microencapsulated probiotics plus quercetin reduced body weight loss and intestinal bleeding in ApcMin/+ mice. An improvement in energy expenditure was observed after 8 weeks but not after 10 weeks of treatment. A supplemented diet with microencapsulated Bf and Lg reduced the number of aberrant crypt foci (ACF) and adenomas by 45% and 60%, respectively, whereas the supplementation with Bf, Lg and quercetin decreased the number of ACF and adenomas by 57% and 80%, respectively. Microencapsulated Bf and Lg in combination with quercetin could exert inhibition of the canonical Wnt/β-catenin signaling pathway in the colon of ApcMin/+ mice Conclusions: The administration of microencapsulated Bf and Lg, individually or in combination with quercetin, inhibits the CRC development in ApcMin/+ mice.
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Affiliation(s)
- Iván Benito
- Laboratory of Animal Physiology and Nutrition, School of Agronomy, Public University of Navarre, Campus Arrosadia, 31006 Pamplona, Spain; (I.B.); (M.A.)
| | - Ignacio J. Encío
- Biochemistry Area, Department of Health Science, Public University of Navarre, 31008 Pamplona, Spain;
| | - Fermín I. Milagro
- Department of Nutrition, Food Sciences and Physiology, Center for Nutrition Research, University of Navarra, C/Irunlarrea 1, 31008 Pamplona, Spain;
- Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - María Alfaro
- Laboratory of Animal Physiology and Nutrition, School of Agronomy, Public University of Navarre, Campus Arrosadia, 31006 Pamplona, Spain; (I.B.); (M.A.)
| | | | - Miguel Barajas
- Biochemistry Area, Department of Health Science, Public University of Navarre, 31008 Pamplona, Spain;
| | - Florencio Marzo
- Laboratory of Animal Physiology and Nutrition, School of Agronomy, Public University of Navarre, Campus Arrosadia, 31006 Pamplona, Spain; (I.B.); (M.A.)
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17
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Hanus M, Parada-Venegas D, Landskron G, Wielandt AM, Hurtado C, Alvarez K, Hermoso MA, López-Köstner F, De la Fuente M. Immune System, Microbiota, and Microbial Metabolites: The Unresolved Triad in Colorectal Cancer Microenvironment. Front Immunol 2021; 12:612826. [PMID: 33841394 PMCID: PMC8033001 DOI: 10.3389/fimmu.2021.612826] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 03/02/2021] [Indexed: 12/16/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide. As with other cancers, CRC is a multifactorial disease due to the combined effect of genetic and environmental factors. Most cases are sporadic, but a small proportion is hereditary, estimated at around 5-10%. In both, the tumor interacts with heterogeneous cell populations, such as endothelial, stromal, and immune cells, secreting different signals (cytokines, chemokines or growth factors) to generate a favorable tumor microenvironment for cancer cell invasion and metastasis. There is ample evidence that inflammatory processes have a role in carcinogenesis and tumor progression in CCR. Different profiles of cell activation of the tumor microenvironment can promote pro or anti-tumor pathways; hence they are studied as a key target for the control of cancer progression. Additionally, the intestinal mucosa is in close contact with a microorganism community, including bacteria, bacteriophages, viruses, archaea, and fungi composing the gut microbiota. Aberrant composition of this microbiota, together with alteration in the diet-derived microbial metabolites content (such as butyrate and polyamines) and environmental compounds has been related to CRC. Some bacteria, such as pks+ Escherichia coli or Fusobacterium nucleatum, are involved in colorectal carcinogenesis through different pathomechanisms including the induction of genetic mutations in epithelial cells and modulation of tumor microenvironment. Epithelial and immune cells from intestinal mucosa have Pattern-recognition receptors and G-protein coupled receptors (receptor of butyrate), suggesting that their activation can be regulated by intestinal microbiota and metabolites. In this review, we discuss how dynamics in the gut microbiota, their metabolites, and tumor microenvironment interplays in sporadic and hereditary CRC, modulating tumor progression.
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Affiliation(s)
- Michelle Hanus
- Laboratory of Innate Immunity, Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
| | - Daniela Parada-Venegas
- Laboratory of Innate Immunity, Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
| | - Glauben Landskron
- Laboratory of Innate Immunity, Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
| | | | - Claudia Hurtado
- Research Core, Academic Department, Clínica Las Condes, Santiago, Chile
| | - Karin Alvarez
- Cancer Center, Clínica Universidad de los Andes, Santiago, Chile
| | - Marcela A. Hermoso
- Laboratory of Innate Immunity, Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
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18
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The Western Dietary Pattern Combined with Vancomycin-Mediated Changes to the Gut Microbiome Exacerbates Colitis Severity and Colon Tumorigenesis. Nutrients 2021; 13:nu13030881. [PMID: 33803094 PMCID: PMC8000903 DOI: 10.3390/nu13030881] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 03/01/2021] [Accepted: 03/04/2021] [Indexed: 02/06/2023] Open
Abstract
Previous work by our group using a mouse model of inflammation-associated colorectal cancer (CAC) showed that the total Western diet (TWD) promoted colon tumor development. Others have also shown that vancomycin-mediated changes to the gut microbiome increased colorectal cancer (CRC). Therefore, the objective of this study was to determine the impact of vancomycin on colon tumorigenesis in the context of a standard mouse diet or the TWD. A 2 × 2 factorial design was used, in which C57Bl/6J mice were fed either the standard AIN93G diet or TWD and with vancomycin in the drinking water or not. While both the TWD and vancomycin treatments independently increased parameters associated with gut inflammation and tumorigenesis compared to AIN93G and plain water controls, mice fed the TWD and treated with vancomycin had significantly increased tumor multiplicity and burden relative to all other treatments. Vancomycin treatment significantly decreased alpha diversity and changed the abundance of several taxa at the phylum, family, and genus levels. Conversely, basal diet had relatively minor effects on the gut microbiome composition. These results support our previous research that the TWD promotes colon tumorigenesis and suggest that vancomycin-induced changes to the gut microbiome are associated with higher tumor rates.
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19
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Rai N, Singh AK, Keshri PK, Barik S, Kamble SC, Singh SK, Kumar R, Mishra P, Kotiya D, Gautam V. Probiotics for Management of Gastrointestinal Cancers. PROBIOTIC RESEARCH IN THERAPEUTICS 2021:191-209. [DOI: 10.1007/978-981-15-8214-1_9] [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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20
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Samanta S. Potential Impacts of Prebiotics and Probiotics in Cancer Prevention. Anticancer Agents Med Chem 2020; 22:605-628. [PMID: 33305713 DOI: 10.2174/1871520621999201210220442] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 09/15/2020] [Accepted: 10/26/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cancer is a serious problem throughout the world. The pathophysiology of cancer is multifactorial and is also related to gut microbiota. Intestinal microbes are the useful resident of the healthy human. They play various aspects of human health including nutritional biotransformation, flushing of the pathogens, toxin neutralization, immune response, and onco-suppression. Disruption in the interactions among the gut microbiota, intestinal epithelium, and the host immune system are associated with gastrointestinal disorders, neurodegenerative diseases, metabolic syndrome, and cancer. Probiotic bacteria (Lactobacillus spp., Bifidobacterium spp.) have been regarded as beneficial to health and shown to play a significant role in immunomodulation and displayed preventive role against obesity, diabetes, liver disease, inflammatory bowel disease, tumor progression, and cancer. OBJECTIVE The involvement of gut microorganisms in cancer development and prevention has been recognized as a balancing factor. The events of dysbiosis emphasize metabolic disorder and carcinogenesis. The gut flora potentiates immunomodulation and minimizes the limitations of usual chemotherapy. The significant role of prebiotics and probiotics on the improvement of immunomodulation and antitumor properties has been considered. METHODS I had reviewed the literature on the multidimensional activities of prebiotics and probiotics from the NCBI website database PubMed, Springer Nature, Science Direct (Elsevier), Google Scholar database to search relevant articles. Specifically, I had focused on the role of prebiotics and probiotics in immunomodulation and cancer prevention. RESULTS Prebiotics are the nondigestible fermentable sugars that selectively influence the growth of probiotic organisms that exert immunomodulation over the cancerous growth. The oncostatic properties of bacteria are mediated through the recruitment of cytotoxic T cells, natural killer cells, and oxidative stress-induced apoptosis in the tumor microenvironment. Moreover, approaches have also been taken to use probiotics as an adjuvant in cancer therapy. CONCLUSION The present review has indicated that dysbiosis is the crucial factor in many pathological situations including cancer. Applications of prebiotics and probiotics exhibit the immune-surveillance as oncostatic effects. These events increase the possibilities of new therapeutic strategies for cancer prevention.
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Affiliation(s)
- Saptadip Samanta
- Department of Physiology, Midnapore College, Midnapore, Paschim Medinipur, 721101, West Bengal,. India
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21
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Brasiel PGDA, Dutra Luquetti SCP, Peluzio MDCG, Novaes RD, Gonçalves RV. Preclinical Evidence of Probiotics in Colorectal Carcinogenesis: A Systematic Review. Dig Dis Sci 2020; 65:3197-3210. [PMID: 31960202 DOI: 10.1007/s10620-020-06062-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 01/09/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Colorectal cancer, the second major cause of cancer deaths, imposes a major health burden worldwide. There is growing evidence that supports that the use of probiotics is effective against various diseases, especially in gastrointestinal diseases, including the colorectal cancer, but the differences between the strains, dose, and frequency used are not yet clear. AIMS To perform a systematic review to compile the results of studies carried out in animal models and investigated the effect of probiotics on colorectal carcinogenesis. METHODS Studies were selected in PubMed/MEDLINE and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search filters were developed using three parameters: probiotics, colorectal cancer, and animal model. RESULTS From a structured search, we discovered 34 original articles and submitted them to a risk of bias analysis using SYRCLE's tool. The studies show a great diversity of models, most were conducted in rats (55.8%) and used 1,2 dimethylhydrazine as the drug to induce colorectal carcinogenesis (61.7%). The vast majority of trials investigated Lactobacillus (64%) and Bifidobacterium (29.4%) strains. Twenty-six (86.6%) studies found significant reduction in lesions or tumors in the animals that received probiotics. The main methodological limitation was the insufficient amount of information for the adequate reproducibility of the trials, which indicated a high risk of bias due to incomplete characterization of the experimental design. CONCLUSIONS The different probiotics' strains showed anti-carcinogenic effect, reduced the development of lesions and intestinal tumors, antioxidant and immunomodulatory activity, and reduced fecal bacterial enzymes.
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Affiliation(s)
| | | | | | - Rômulo Dias Novaes
- Department of Structural Biology, Federal University of Alfenas, Alfenas, MG, Brazil
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22
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Dong Y, Zhu J, Zhang M, Ge S, Zhao L. Probiotic Lactobacillus salivarius Ren prevent dimethylhydrazine-induced colorectal cancer through protein kinase B inhibition. Appl Microbiol Biotechnol 2020; 104:7377-7389. [PMID: 32666185 DOI: 10.1007/s00253-020-10775-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 06/24/2020] [Accepted: 07/05/2020] [Indexed: 02/06/2023]
Abstract
Probiotics are known to be a potential agent for colorectal cancer (CRC) inhibition, but the precise mechanisms by which probiotic exert anti-tumorigenic effects remain to be explored. Lactobacillus salivarius (LS) Ren was isolated from centenarians living in Bama of China, which showed an anticancer potent in animal model of oral cancer. Here, we investigated the effect of LS on colorectal carcinogenesis and its putative mechanism. Oral administration of LS effectively suppressed the formation of dimethylhydrazine (DMH)-induced CRC in both initial and post-initial stages. Significant antiproliferation and proapoptotic effects were observed with inhibition of tumor formation by dietary intake of LS. Besides, LS metabolites inhibited growth, arrested cell cycle, and induced apoptosis of HT-29 cells. Furthermore, upon the treatment of LS, protein kinase B (AKT) phosphorylation and the downstream proteins of cyclinD1 and cyclooxygenase-2 (COX-2) were significantly downregulated in both in vivo and in vitro tests. These results showed that LS inhibited the colorectal carcinogenesis through suppressing AKT signaling pathway, resulting in suppressing cell proliferation and inducing cell apoptosis. Our findings suggest that this probiotic may act as a prophylactic agent for CRC prevention. Key points • LS effectively prevented rat colorectal carcinogenesis induced by DMH. • LS modulated the proliferation and apoptosis in both in vivo and in vitro. • LS inhibited AKT phosphorylation and expressions of downstream cyclinD1 and COX-2.
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Affiliation(s)
- Yuanyuan Dong
- School of Food and Chemical Engineering, Beijing Technology and Business University, Beijing, 100048, China
| | - Jun Zhu
- Research Center for Probiotics, China Agricultural University, Beijing, 100083, China.,Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, 100083, China
| | - Ming Zhang
- School of Food and Chemical Engineering, Beijing Technology and Business University, Beijing, 100048, China. .,Research Center for Probiotics, China Agricultural University, Beijing, 100083, China.
| | - Shaoyang Ge
- Beijing Laboratory for Food Quality and Safety, China Agricultural University, Beijing, 100083, China
| | - Liang Zhao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.,Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China
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Elsalem L, Jum'ah AA, Alfaqih MA, Aloudat O. The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives. Clin Exp Gastroenterol 2020; 13:151-185. [PMID: 32440192 PMCID: PMC7211962 DOI: 10.2147/ceg.s243337] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 04/13/2020] [Indexed: 12/24/2022] Open
Abstract
The microbiota has an essential role in the pathogenesis of many gastrointestinal diseases including cancer. This effect is mediated through different mechanisms such as damaging DNA, activation of oncogenic pathways, production of carcinogenic metabolites, stimulation of chronic inflammation, and inhibition of antitumor immunity. Recently, the concept of "pharmacomicrobiomics" has emerged as a new field concerned with exploring the interplay between drugs and microbes. Mounting evidence indicates that the microbiota and their metabolites have a major impact on the pharmacodynamics and therapeutic responses toward anticancer drugs including conventional chemotherapy and molecular-targeted therapeutics. In addition, microbiota appears as an attractive target for cancer prevention and treatment. In this review, we discuss the role of bacterial microbiota in the pathogenesis of different cancer types affecting the gastrointestinal tract system. We also scrutinize the evidence regarding the role of microbiota in anticancer drug responses. Further, we discuss the use of probiotics, fecal microbiota transplantation, and antibiotics, either alone or in combination with anticancer drugs for prevention and treatment of gastrointestinal tract cancers.
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Affiliation(s)
- Lina Elsalem
- Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Ahmad A Jum'ah
- Department of Conservative Dentistry, Faculty of Dentistry, Jordan University of Science and Technology, Irbid, Jordan
| | - Mahmoud A Alfaqih
- Department of Physiology and Biochemistry, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Osama Aloudat
- Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
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Administration of Bifidobacterium bifidum CGMCC 15068 modulates gut microbiota and metabolome in azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated colon cancer (CAC) in mice. Appl Microbiol Biotechnol 2020; 104:5915-5928. [PMID: 32367312 DOI: 10.1007/s00253-020-10621-z] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Revised: 03/31/2020] [Accepted: 04/09/2020] [Indexed: 12/31/2022]
Abstract
The gut microbiota plays an important role in colorectal cancer (CRC), and the use of probiotics might be a promising intervention method. The aim of our study was to investigate the beneficial effect of Bifidobacterium bifidum CGMCC 15068 on an azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated CRC (CAC) mouse model. CAC was induced by an intra-peritoneal injection of AOM (10 mg/kg) and three 7-day cycles of 2% DSS in drinking water with a 14-day recovery period between two consecutive DSS administrations. B. bifidum CGMCC 15068 (3 × 109 CFU/mL) was gavaged once daily during the recovery period. Then, the faecal microbial composition and metabolome were profiled using the 16S rRNA sequencing technology and gas chromatography-mass spectrometry (GC-MS), respectively. The administration of B. bifidum CGMCC 15068 attenuated tumourigenesis in the CAC mouse model. In addition, B. bifidum CGMCC 15068 pre-treatment increased the relative abundance of Akkermansia, Desulfovibrionaceae, Romboutsia, Turicibacter, Verrucomicrobiaceae, Ruminococcaceae_UCG_013, Lachnospiraceae_UCG_004, and Lactobacillus. Meanwhile, B. bifidum CGMCC 15068 altered metabolites involved in the citrate cycle (TCA cycle), glycolysis, butyrate metabolism, fatty acid biosynthesis, and galactose metabolism. Several significant correlations were identified between the differentially abundant microbes and metabolites. These findings supported the beneficial role of B. bifidum CGMCC 15068 in intestinal health by modulating dysbiosis and the gut metabolic profile. The manipulation of the gut microbial composition using probiotics might be a promising prevention strategy for CRC. Long-term and large-scale clinical trials are warranted for the potential clinical applications of this strategy in the future.
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A novel kefir product (PFT) inhibits Ehrlich ascites carcinoma in mice via induction of apoptosis and immunomodulation. BMC Complement Med Ther 2020; 20:127. [PMID: 32345289 PMCID: PMC7189677 DOI: 10.1186/s12906-020-02901-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Accepted: 03/23/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND The popularity of fermented foods such as kefir, kuniss, and tofu has been greatly increasing over the past several decades, and the ability of probiotic bacteria to exert anticancer effects has recently become the focus of research. While we have recently demonstrated the ability of the novel kefir product PFT (Probiotics Fermentation Technology) to exert anticancer effects in vitro, here we demonstrate its ability to inhibit Ehrlich ascites carcinoma (EAC) in mice. METHODS Mice were inoculated intramuscularly with EAC cells to develop solid tumors. PFT was administered orally (2 g/kg/day) to mice 6 days/week, either 2 days before tumor cell inoculation or 9 days after inoculation to mice bearing solid tumors. Tumor growth, blood lymphocyte levels, cell cycle progression, apoptosis, apoptotic regulator expression, TNF-α expression, changes in mitochondrial membrane potential (MMP), PCNA, and CD4+ and CD8+ T cells in tumor cells were quantitatively evaluated by flow cytometry or RT-PCR. Further studies in vitro were carried out where EAC cells along with several other human cancer cell lines were cultured in the presence of PFT (0-5 mg/mL). Percent cell viability and IC50 was estimated by MTT assay. RESULTS Our data shows that PFT exerts the following: 1) inhibition of tumor incidence and tumor growth; 2) inhibition of cellular proliferation via a marked decrease in the expression of tumor marker PCNA; 3) arrest of the tumor cell cycle in the sub-G0/G1 phase, signifying apoptosis; 4) induction of apoptosis in cancer cells via a mitochondrial-dependent pathway as indicated by the up-regulation of p53 expression, increased Bax/Bcl-2 ratio, decrease in the polarization of MMP, and caspase-3 activation; and 5) immunomodulation with an increase in the number of infiltrating CD4+ and CD8+ T cells and an enhancement of TNF-α expression within the tumor. CONCLUSIONS PFT reduces tumor incidence and tumor growth in mice with EAC by inducing apoptosis in EAC cells via the mitochondrial-dependent pathway, suppressing cancer cell proliferation, and stimulating the immune system. PFT may be a useful agent for cancer prevention.
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Settanni CR, Quaranta G, Bibbò S, Gasbarrini A, Cammarota G, Ianiro G. Oral supplementation with lactobacilli to prevent colorectal cancer in preclinical models. MINERVA GASTROENTERO 2019; 66:48-69. [PMID: 31760735 DOI: 10.23736/s1121-421x.19.02631-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Colorectal cancer (CRC) is still a major threat for public health, as it is the third most common cancer in men and the second in women and it ranks second among tumors in terms of mortality. Evidence from the last decades emphasizes the complex role of gut microbial composition in CRC development. Historically, it is believed that dairy products, a source of lactobacilli and other lactic acid bacteria, are beneficial for human health and help in preventing CRC. We searched online literature for trials evaluating the preventive role of lactobacilli in CRC animal models. Most of selected studied assessed a relevant role of lactobacilli in preventing CRC and precursor lesions. Mechanisms through which this effect was achieved are supposed to regard immunomodulation, regulation of apoptosis, gut microbial modulation, genes expression, reduction of oxidative stress and others. Lactobacilli oral supplementation is reported to be effective in preventing CRC in animal models, even if the underlying mechanisms of action are still not fully understood.
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Affiliation(s)
- Carlo R Settanni
- Digestive Disease Center, Agostino Gemelli University Polyclinic, IRCCS and Foundation, Sacred Heart Catholic University, Rome, Italy
| | - Gianluca Quaranta
- Institute of Microbiology, Agostino Gemelli University Polyclinic, IRCCS and Foundation, Sacred Heart Catholic University, Rome, Italy
| | - Stefano Bibbò
- Digestive Disease Center, Agostino Gemelli University Polyclinic, IRCCS and Foundation, Sacred Heart Catholic University, Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center, Agostino Gemelli University Polyclinic, IRCCS and Foundation, Sacred Heart Catholic University, Rome, Italy
| | - Giovanni Cammarota
- Digestive Disease Center, Agostino Gemelli University Polyclinic, IRCCS and Foundation, Sacred Heart Catholic University, Rome, Italy
| | - Gianluca Ianiro
- Digestive Disease Center, Agostino Gemelli University Polyclinic, IRCCS and Foundation, Sacred Heart Catholic University, Rome, Italy -
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Karimi Ardestani S, Tafvizi F, Tajabadi Ebrahimi M. Heat-killed probiotic bacteria induce apoptosis of HT-29 human colon adenocarcinoma cell line via the regulation of Bax/Bcl2 and caspases pathway. Hum Exp Toxicol 2019; 38:1069-1081. [PMID: 31117840 DOI: 10.1177/0960327119851255] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Apoptosis induction in cancer cells is one of the most efficient ways to treat cancer and find anticancer compounds. The aim of this study was to evaluate the cytotoxic effects of heat-killed indigenous probiotic bacteria and apoptosis induction in the HT-29 human colon adenocarcinoma cell line. The growth-inhibitory effects of probiotic heat-killed Lactobacillus brevis and Lactobacillus paracasei isolated from the traditional Iranian food "Terxine" on the HT-29 cell line were determined by 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry by Annexin-FITC kit, DNA fragmentation assay, 4,6-diamidino-2-phenylindole staining, and the expression of Bax, Bcl2, caspase-3, and caspase-9 were used to analyze apoptosis. MTT results demonstrated that the heat-killed bacteria inhibited the proliferation of HT-29 cells and induced apoptosis in a time-, dose-, and strain-dependent manner. The results demonstrated that both bacteria could induce apoptosis in the HT-29 cell line. Heat-killed probiotic bacteria increased the expression of Bax, caspase-3, and caspase-9 mRNA levels in HT-29 cell lines. Also, heat-killed probiotic bacteria reduced the expression of Bcl2 in HT-29 cells. The heat-killed probiotic bacteria in this study exhibited potent growth inhibitory effects on cancer cells. The results demonstrated that L. brevis has a greater ability to inhibit the growth of HT-29 cells and induce apoptosis, compared with L. paracasei. It is proposed that these bacteria can be used as biological products for the treatment and prevention of cancer, pending further investigation.
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Affiliation(s)
- S Karimi Ardestani
- 1 Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran
| | - F Tafvizi
- 1 Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran
| | - M Tajabadi Ebrahimi
- 2 Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran
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Gavresea F, Vagianos C, Korontzi M, Sotiropoulou G, Dadioti P, Triantafillidis JK, Papalois AE. Beneficial effect of synbiotics on experimental colon cancer in rats. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 29:494-501. [PMID: 30249566 DOI: 10.5152/tjg.2018.17469] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND/AIMS The aim of this study was to investigate the influence of a synbiotic preparation (a mixture of six probiotics and a prebiotic) on aberrant crypt foci (ACF) formation, dysplasia, inflammation, and colitis-like lesions in experimental colon cancer in rats. MATERIALS AND METHODS Sixty male rats were categorized into three groups of 20 animals each. Group A was administered 1,2-dimethylydrazine, 15 mg/kg body weight (BW), once a week for 2 weeks. Group B was administered 1,2-dimethylydrazine at the same dose plus synbiotic, started after the second dose of carcinogen and lasted for 5 weeks. Group C was administered synbiotic plus carcinogen from the beginning of the experiment and lasted for 7 weeks. Animals were killed at the end of week 7. RESULTS At the end of the experiment, the animals that received carcinogen plus the synbiotic had 100%, whereas the animals that received only carcinogen has 70% survival. Animals of groups B and C had significantly lower percentage of inflammation, colitis-like lesions, and ACF dysplasia than animals of group A, whereas those of group C had the least pathological lesions. CONCLUSION Synbiotics seem to protect against the appearance of preneoplastic colon lesions in rats. The results of this experimental study suggest that treatment with a synbiotic preparation exerts significant antimutagenic properties against the development of preneoplastic lesions in rats.
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Affiliation(s)
- Fani Gavresea
- Department of Pathology, Metaxas Cancer Hospital, Piraeus, Greece
| | - Costas Vagianos
- Department of Surgery, University of Athens Laiko Hospital, Athens, Greece
| | - Maria Korontzi
- Experimental-Research Laboratory, ELPEN Pharma, Athens, Greece
| | | | - Petroula Dadioti
- Department of Pathology, Metaxas Cancer Hospital, Piraeus, Greece
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dos Reis SA, da Conceição LL, e Dias MM, Siqueira NP, Rosa DD, de Oliveira LL, da Matta SLP, Peluzio MDCG. Kefir reduces the incidence of pre-neoplastic lesions in an animal model for colorectal cancer. J Funct Foods 2019. [DOI: 10.1016/j.jff.2018.11.050] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
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Saccharomyces cerevisiae inhibits growth and metastasis and stimulates apoptosis in HT-29 colorectal cancer cell line. ACTA ACUST UNITED AC 2018. [DOI: 10.1007/s00580-018-2855-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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Nazir Y, Hussain SA, Abdul Hamid A, Song Y. Probiotics and Their Potential Preventive and Therapeutic Role for Cancer, High Serum Cholesterol, and Allergic and HIV Diseases. BIOMED RESEARCH INTERNATIONAL 2018; 2018:3428437. [PMID: 30246019 PMCID: PMC6136537 DOI: 10.1155/2018/3428437] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 07/12/2018] [Accepted: 08/07/2018] [Indexed: 12/20/2022]
Abstract
The potential health benefits of probiotics have long been elucidated since Metchnikoff and his coworkers postulated the association of probiotic consumption on human's health and longevity. Since then, many scientific findings and research have further established the correlation of probiotic and gut-associated diseases such as irritable bowel disease and chronic and antibiotic-associated diarrhea. However, the beneficial impact of probiotic is not limited to the gut-associated diseases alone, but also in different acute and chronic infectious diseases. This is due to the fact that probiotics are able to modify the intestinal microbial ecosystem, enhance the gut barrier function, provide competitive adherence to the mucosa and epithelium, produce antimicrobial substances, and modulate the immune activity by enhancing the innate and adaptive immune response. Nevertheless, the current literature with respect to the association of probiotic and cancer, high serum cholesterol, and allergic and HIV diseases are still scarce and controversial. Therefore, in the present work, we reviewed the potential preventive and therapeutic role of probiotics for cancer, high serum cholesterol, and allergic and HIV diseases as well as providing its possible mechanism of actions.
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Affiliation(s)
- Yusuf Nazir
- Colin Ratledge Center for Microbial Lipids, School of Agriculture Engineering and Food Science, Shandong University of Technology, Zibo 255049, China
| | - Syed Ammar Hussain
- Colin Ratledge Center for Microbial Lipids, School of Agriculture Engineering and Food Science, Shandong University of Technology, Zibo 255049, China
| | - Aidil Abdul Hamid
- School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Malaysia
| | - Yuanda Song
- Colin Ratledge Center for Microbial Lipids, School of Agriculture Engineering and Food Science, Shandong University of Technology, Zibo 255049, China
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Jacouton E, Chain F, Sokol H, Langella P, Bermúdez-Humarán LG. Probiotic Strain Lactobacillus casei BL23 Prevents Colitis-Associated Colorectal Cancer. Front Immunol 2017; 8:1553. [PMID: 29209314 PMCID: PMC5702231 DOI: 10.3389/fimmu.2017.01553] [Citation(s) in RCA: 139] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 10/31/2017] [Indexed: 12/16/2022] Open
Abstract
The gut microbiota plays a major role in intestinal health, and an imbalance in its composition can lead to chronic gut inflammation and a predisposition to developing colorectal cancer (CRC). Currently, the use of probiotic bacteria represents an emerging alternative to treat and prevent cancer. Moreover, consumption of these beneficial bacteria may also favorably modulate the composition of the gut microbiota, which has been described in several studies to play an important role in CRC carcinogenesis. In this context, the aim of this study was to assess the protective effect of oral treatment with Lactobacillus casei BL23, a probiotic strain well known for its anti-inflammatory and anticancer properties. First, CRC was induced in C57BL6 mice by a single intraperitoneal injection with azoxymethane (8 mg/kg), followed by four courses of dextran sodium sulfate (2.5%) in drinking water that were separated by an adjustable recovery period. At the time of sacrifice (day 46), tumor incidence, histological scores, and epithelial proliferation were determined in colon samples. Our results show that L. casei BL23 significantly protected mice against CRC development; specifically, L. casei BL23 treatment reduced histological scores and proliferative index values. In addition, our analysis revealed that L. casei BL23 had an immunomodulatory effect, mediated through the downregulation of the IL-22 cytokine, and an antiproliferative effect, mediated through the upregulation of caspase-7, caspase-9, and Bik. Finally, L. casei BL23 treatment tended to counterbalance CRC-induced dysbiosis in mice, as demonstrated by an analysis of fecal microbiota. Altogether our results demonstrate the high potential of L. casei BL23 for the development of new, probiotic-based strategies to fight CRC.
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Affiliation(s)
- Elsa Jacouton
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Florian Chain
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Harry Sokol
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.,Sorbonne Universités, UPMC Univ. Paris 06, École normale supérieure, CNRS, INSERM, APHP Laboratoire des Biomolécules (LBM), Paris, France
| | - Philippe Langella
- Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
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Lactobacillus delbrueckii subsp. lactis (strain CIDCA 133) stimulates murine macrophages infected with Citrobacter rodentium. World J Microbiol Biotechnol 2017; 33:48. [PMID: 28176201 DOI: 10.1007/s11274-017-2219-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Accepted: 01/28/2017] [Indexed: 10/20/2022]
Abstract
Citrobacter rodentium is a specific murine enteropathogen which causes diarrheal disease characterized by colonic hyperplasia and intestinal inflammation. Recruitment of neutrophils and macrophages constitute a key step to control the infection. Since modulation of the activity of professional phagocytic cells could contribute to improve host´s defences against C. rodentium, we investigated the effect of Lactobacillus delbrueckii subsp. lactis (strain CIDCA 133) on the interaction between murine macrophages (RAW 264.7) and C. rodentium. Phagocytosis, surface molecules and inducible nitric oxide synthase (iNOs) expression were determined by flow cytometry. Reactive oxygen species (ROS) were assessed by fluorescence microscopy. The presence of lactobacilli increased phagocytosis of C. rodentium whereas C. rodentium had no effect on lactobacilli internalization. Survival of internalized C. rodentium diminished when strain CIDCA 133 was present. CD-86, MHCII, iNOs expression and nitrite production were increased when C. rodentium and lactobacilli were present even though strain CIDCA 133 alone had no effect. Strain CIDCA 133 led to a strong induction of ROS activity which was not modified by C. rodentium. Lactobacillus delbrueckii subsp. lactis (strain CIDCA 133) is able to increase the activation of murine macrophages infected with C. rodentium. The sole presence of lactobacilli is enough to modify some stimulation markers (e.g. ROS induction) whereas other markers require the presence of both bacteria; thus, indicating a synergistic effect.
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Dos Reis SA, da Conceição LL, Siqueira NP, Rosa DD, da Silva LL, Peluzio MDCG. Review of the mechanisms of probiotic actions in the prevention of colorectal cancer. Nutr Res 2016; 37:1-19. [PMID: 28215310 DOI: 10.1016/j.nutres.2016.11.009] [Citation(s) in RCA: 123] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Revised: 11/16/2016] [Accepted: 11/18/2016] [Indexed: 12/16/2022]
Abstract
The purpose of this review is to discuss the potential mechanisms of probiotics action in colorectal cancer prevention. In this regard, the composition of the intestinal microbiota is considered as an important risk factor in the development of colorectal cancer, and probiotics are able to positively modulate the composition of this microbiota. Studies have shown that the regular consumption of probiotics could prevent the development of colorectal cancer. In this respect, in vitro and experimental studies suggest some potential mechanisms responsible for this anticarcinogenic action. The mechanisms include modification of the intestinal microbiota composition, changes in metabolic activity of the microbiota, binding and degradation of carcinogenic compounds present in the intestinal lumen, production of compounds with anticarcinogenic activity, immunomodulation, improvement of the intestinal barrier, changes in host physiology, inhibition of cell proliferation, and induction of apoptosis in cancer cells. In contrast, very few reports demonstrate adverse effects of probiotic oral supplementation. In light of the present evidence, more specific studies are needed on probiotic bacteria, especially regarding the identification of the bacterial strains with greater anticarcinogenic potential; the verification of the viability of these strains after passing through the gastrointestinal tract; the investigation of potential adverse effects in immunocompromised individuals; and finally establishing the dosage and frequency of use.
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Affiliation(s)
- Sandra A Dos Reis
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil.
| | - Lisiane L da Conceição
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil.
| | - Nathane P Siqueira
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil.
| | - Damiana D Rosa
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil.
| | - Letícia L da Silva
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil.
| | - Maria do Carmo G Peluzio
- Department of Nutrition and Health, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 36570-900, Brazil.
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35
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Yu AQ, Li L. The Potential Role of Probiotics in Cancer Prevention and Treatment. Nutr Cancer 2016; 68:535-44. [PMID: 27144297 DOI: 10.1080/01635581.2016.1158300] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The human gut microbiota has a significant effect on many aspects of human physiology such as metabolism, nutrient absorption, and immune function. Imbalance of the microbiota has been implicated in many disorders including inflammatory bowel disease, obesity, asthma, psychiatric illnesses, and cancers. As a kind of functional foods, probiotics have been shown to play a protective role against cancer development in animal models. Clinical application of probiotics indicated that some probiotic strains could diminish the incidence of postoperative inflammation in cancer patients. Chemotherapy or radiotherapy-related diarrhea was relieved in patients who were administered oral probiotics. The present review summarizes the up-to-date studies on probiotic effects and the underlying mechanisms related to cancer. At present, it is commonly accepted that most commercial probiotic products are generally safe and can improve the health of the host. By modulating intestinal microbiota and immune response, some strains of probiotics can be used as an adjuvant for cancer prevention or/and treatment.
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Affiliation(s)
- Ai-Qun Yu
- a Institute of Psychology, Chinese Academy of Sciences , Beijing , China.,b Graduate School of Chinese Academy of Sciences , Beijing , China.,c Shanghai Lida Polytechnic Institute , Shanghai , China
| | - Lianqin Li
- d Department of Obstetrics and Gynecology , Yantai Affiliated Hospital of Binzhou Medical University , Yantai , China
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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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Abstract
In nutraceutical science, the ingestible live microbes 'probiotics' are regarded for their ability to confer multiplicity of health benefits on the consumers. Wide spectrum impact of these friendly microbes on the host health has been proved very frequently. They have been confirmed to boost immunity, aid in digestion, eliminate pathogens, curb inflammatory bowel diseases, moderate side effects of antibiotic therapy, lower cholesterol and blood glycemic index and produce vitamins. This review, however, focuses on the incipient, but promising area of probiotic diet-based prevention and remedy of cancer. Researchers are in universal agreement with the critical role of probiotics in getting rid of mutagens, delaying the onset of tumors, alleviating the side effects, pepping up chemotherapy, easing the postoperative complications, foiling remission and lifting the spirit of survivors. The key findings in the emerging roles of probiotics in onco-care have been summarized; the biological pathways discussed and anticipated developments in coming times are presented.
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Liao W, Luo Z, Liu D, Ning Z, Yang J, Ren J. Structure characterization of a novel polysaccharide from Dictyophora indusiata and its macrophage immunomodulatory activities. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2015; 63:535-544. [PMID: 25525995 DOI: 10.1021/jf504677r] [Citation(s) in RCA: 185] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
A novel polysaccharide, here named DP1, was isolated from the fruiting body of Dictyophora indusiata using a water extraction method. Structure characterization revealed that DP1 had an average molecular weight of 1132 kDa and consisted of glucose (56.2%), galactose (14.1%), and mannose (29.7%). The main linkage type of DP1 were proven to be (1 → 3)-linked α-l-Man, (1 → 2,6)-linked α-d-Glc, (1 → 6)-linked β-d-Glc, (1 → 6)-linked β-d-Gal, and (1 → 6)-linked β-d-Man by periodate oxidation-Smith degradation and nuclear magnetic resonance analysis. The immunostimulating assay indicated that DP1 could significantly promote macrophage NO, TNF-α, and IL-6 secretion in murine RAW 264.7 cells involving complement receptor 3 (CR3). The immune activities of DP1 were quite stable under thermal processing (100, 121, and 145 °C). Besides, DP1 retained stability after acidic/alkline treatment (pH 4.0-10.0), which enabled it to be an ideal complementary medicine or functional food for therapeutics of hypoimmunity and immunodeficiency diseases.
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Affiliation(s)
- Wenzhen Liao
- College of Light Industry and Food Sciences, South China University of Technology , Guangzhou, Guangdong 510640, People's Republic of China
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Russo F, Linsalata M, Orlando A. Probiotics against neoplastic transformation of gastric mucosa: Effects on cell proliferation and polyamine metabolism. World J Gastroenterol 2014; 20:13258-13272. [PMID: 25309063 PMCID: PMC4188884 DOI: 10.3748/wjg.v20.i37.13258] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Revised: 04/02/2014] [Accepted: 06/05/2014] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.
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In vitro assessment of agave fructans (Agave salmiana) as prebiotics and immune system activators. Int J Biol Macromol 2014; 63:181-7. [DOI: 10.1016/j.ijbiomac.2013.10.039] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Revised: 10/20/2013] [Accepted: 10/26/2013] [Indexed: 01/18/2023]
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Abstract
INTRODUCTION Cancers of the gastrointestinal tract account for 25 % of all cancers and for 9 % of all causes of cancer death in the world, so gastrointestinal cancers represent a major health problem. In the past decades, an emerging role has been attributed to the interactions between the gastrointestinal content and the onset of neoplasia. METHODS Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. Probiotics are mono or mixed cultures of live microorganisms that might beneficially affect the host by improving the characteristics of indigenous microflora. Although the effects of probiotic administration has been intensively investigated in vitro, in animal models, in healthy volunteers, and in some human gastrointestinal diseases, very little is still known about the possible cross-interactions among probiotic administration, changes of intestinal flora, and the neoplastic transformation of gastrointestinal mucosa. RESULTS Theoretically, probiotics are able to reduce cancer risk by a number of mechanisms: (a) binding and degradation of potential carcinogens; (b) quantitative, qualitative and metabolic alterations of the intestinal microflora; (c) production of anti-tumorigenic or anti-mutagenic compounds; (d) competitive action towards pathogenic bacteria; (e) enhancement of the host's immune response; (f) direct effects on cell proliferation. CONCLUSION This review will attempt to highlight the literature on the most widely recognized effects of probiotics against neoplastic transformation of gastrointestinal mucosa and in particular on their effects on cell proliferation.
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Affiliation(s)
- Antonella Orlando
- Laboratory of Experimental Biochemistry, National Institute for Digestive Diseases, IRCCS S de Bellis, Via Turi 27, 70013 Castellana Grotte, Bari, Italy
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Khan AA, Khurshid M, Khan S, Alshamsan A. Gut Microbiota and Probiotics: Current Status and Their Role in Cancer Therapeutics. Drug Dev Res 2013. [DOI: 10.1002/ddr.21087] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Affiliation(s)
- Abdul Arif Khan
- Nanomedicine Research Unit; Department of Pharmaceutics; College of Pharmacy; King Saud University; PO Box 2457; Riyadh; 11451; Saudi Arabia
| | - Mohsin Khurshid
- Nanomedicine Research Unit; Department of Pharmaceutics; College of Pharmacy; King Saud University; PO Box 2457; Riyadh; 11451; Saudi Arabia
| | - Shahanavaj Khan
- Nanomedicine Research Unit; Department of Pharmaceutics; College of Pharmacy; King Saud University; PO Box 2457; Riyadh; 11451; Saudi Arabia
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Zhang M, Wang F, Jiang L, Liu R, Zhang L, Lei X, Li J, Jiang J, Guo H, Fang B, Zhao L, Ren F. Lactobacillus Salivarius REN Inhibits Rat Oral Cancer Induced by 4-Nitroquioline 1-Oxide. Cancer Prev Res (Phila) 2013; 6:686-94. [PMID: 23658366 DOI: 10.1158/1940-6207.capr-12-0427] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Ming Zhang
- Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
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Liboredo JC, Anastácio LR, Pelúzio MDCG, Valente FX, Penido LCP, Nicoli JR, Correia MITD. Effect of probiotics on the development of dimethylhydrazine-induced preneoplastic lesions in the mice colon. Acta Cir Bras 2013; 28:367-72. [DOI: 10.1590/s0102-86502013000500008] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2013] [Accepted: 04/16/2013] [Indexed: 01/01/2023] Open
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Rupa P, Mine Y. Recent advances in the role of probiotics in human inflammation and gut health. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:8249-8256. [PMID: 22897745 DOI: 10.1021/jf301903t] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
The gastrointestinal (GI) tract provides residence to an astounding number of bacterial species, which have profound effects on host biology, function, physiology, and immune response. Discovery of "symbiosis factors" from symbionts that facilitate the peaceful coexistence of microbiota and the host immune system are of interest. Symbionts synthesize immunomodulatory molecules that guide maturation of the immune system and have pivotal roles in many biological processes; however, individuals differ in the makeup of their GI microbiota, which is influenced by many external and internal factors such as diet, antibiotic use, and host genetics, which in turn influences health and disease outcomes. Various endogenous, genetic, and environmental factors influence GI development including species composition and health status of neonates, resulting in interactions that occur between the bacteria and the host. Mechanisms of probiotics involved in homeostasis of a balanced immune system have been inconclusive. The probable mechanism of action may be postulated as direct competition between pathogenic bacteria in the gut and/or immune modulation. This review focuses on probiotics in health and disease prevention, especially the biological importance of intestinal regulation of inflammatory processes that may be beneficial in a multitude of disorders both inside and outside the GI tract.
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Affiliation(s)
- Prithy Rupa
- Department of Food Science, University of Guelph , Guelph, Ontario, Canada N1G 2W1
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Cousin FJ, Foligné B, Deutsch SM, Massart S, Parayre S, Le Loir Y, Boudry G, Jan G. Assessment of the probiotic potential of a dairy product fermented by Propionibacterium freudenreichii in piglets. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2012; 60:7917-7927. [PMID: 22823107 DOI: 10.1021/jf302245m] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
Dairy propionibacteria, including Propionibacterium freudenreichii , display promising probiotic properties, including immunomodulation. These properties are highly strain-dependent and rarely studied in a fermented dairy product. We screened 10 strains, grown in a newly developed fermented milk ultrafiltrate, for immunomodulatory properties in vitro. The most anti-inflammatory strain, P. freudenreichii BIA129, was further tested on piglets. P. freudenreichii -fermented product improved food intake and growth of piglets. Colonic mucosa explants of treated pigs secreted less interleukin 8 (-25%, P < 0.05) and tumor necrosis factor α (-20%, P < 0.05), either in basal conditions or after a lipopolysaccharide challenge. By contrast, the gut structure, barrier function (measured ex vivo in Ussing chambers), microbial diversity (assessed by 16S rRNA pyrosequencing), and colonic short-chain fatty acid content were unchanged, assuming maintenance of normal intestinal physiology. In conclusion, this work confirms in vivo probiotic properties of dairy propionibacteria-fermented products, which are promising for the prevention or healing of inflammatory bowel diseases.
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Affiliation(s)
- Fabien J Cousin
- UMR 1253, Science et Technologie du Lait et de l'Œuf, INRA, F-35042 Rennes, France
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