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Avcı E, Avcı GA. Effect of new bioactive substances obtained from possible probiotic bacteria on miRNA expression by in vitro cocultivation in colorectal cancer cells. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2025:1-10. [PMID: 40260513 DOI: 10.1080/09603123.2025.2495195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 04/14/2025] [Indexed: 04/23/2025]
Abstract
In our study, were evaluated effect on colorectal cancer cells of possible probiotic bacteria and new bioactive substances (paraprobiotics/postbiotics), miRNA-expression. Lactobacillus rhamnosus, Lactobacillus reuteri strains, HT-29, and Caco-2 were used. The cytotoxicity of the biotics was determined by MTT and miRNA expression. In line with the data obtained, it was determined that probiotics had a proliferative effect on the fibroblast cell line and a cytotoxic effect on cancer cells. It was observed that paraprobiotics had a minimal effect compared to probiotics, postbiotics had a greater effect. In this work, the activities of new pharmabiotics are compared with living cells, eliminating the limitations of probiotics in terms of shelf life and viability, and thus allowing the creation of new commercial domestic and national products, which increases the unique value of our study. In addition, there will be safer alternatives for suppressed immune systems, and various disadvantages of probiotics can be eliminated.
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Affiliation(s)
- Emre Avcı
- Department of Biochemistry, Faculty of Gulhane Pharmacy, University of Health Sciences, Ankara, Turkiye
| | - Gulcin Alp Avcı
- Department of Basic Medical Sciences, Faculty of Gulhane Dentistry, University of Health Sciences, Ankara, Turkiye
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2
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Papamentzelopoulou M, Pitiriga VC. Unlocking the Interactions Between the Whole-Body Microbiome and HPV Infection: A Literature Review. Pathogens 2025; 14:293. [PMID: 40137778 PMCID: PMC11945791 DOI: 10.3390/pathogens14030293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/12/2025] [Accepted: 03/13/2025] [Indexed: 03/29/2025] Open
Abstract
The human microbiome plays a vital role in maintaining human homeostasis, acting as a key regulator of host immunity and defense mechanisms. However, dysbiotic microbial communities may cause disruption of the symbiotic relationship between the host and the local microbiota, leading to the pathogenesis of various diseases, including viral infections and cancers. One of the most common infectious agents causing cancer is the human papilloma virus (HPV), which accounts for more than 90% of cervical cancers. In most cases, the host immune system is activated and clears HPV, whereas in some cases, the infection persists and can lead to precancerous lesions. Over the last two decades, the advent of next-generation sequencing (NGS) technology and bioinformatics has allowed a thorough and in-depth analysis of the microbial composition in various anatomical niches, allowing researchers to unveil the interactions and the underlying mechanisms through which the human microbiota could affect HPV infection establishment, persistence, and progression. Accordingly, the present narrative review aims to shed light on our understanding of the role of the human microbiome in the context of HPV infection and its progression, mainly to cervical cancer. Furthermore, we explore the mechanisms by which the composition and balance of microbial communities exert potential pathogenic or protective effects, leading to either HPV persistence and disease outcomes or clearance. Special interest is given to how the microbiome can modulate host immunity to HPV infection. Lastly, we summarize the latest findings on the therapeutic efficacy of probiotics and prebiotics in preventing and/or treating HPV infections and the potential of vaginal microbiota transplantation while highlighting the significance of personalized medicine approaches emerging from NGS-based microbiome profiling and artificial intelligence (AI) for the optimal management of HPV-related diseases.
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Affiliation(s)
- Myrto Papamentzelopoulou
- Molecular Biology Unit, 1st Department of Obstetrics and Gynecology, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Vassiliki C. Pitiriga
- Department of Microbiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece
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Taşkoparan Ş, Altınay C, Barbaros Özer H. Recent updates of probiotic dairy-based beverages. Food Funct 2025; 16:1656-1669. [PMID: 39962909 DOI: 10.1039/d4fo06322h] [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: 02/22/2025]
Abstract
There is a rapid paradigm shift in the food consumption habits of consumers globally. The interest in healthier, safer, minimally processed and nature-identical foods is the driving force of this paradigm shift. Although the roots of this consumer trend go back further, especially the Covid-19 pandemic has contributed to the acceleration of this process. The effects of probiotics on human health have been known for many years. The commercial success of some probiotic microorganism strains, supported by clinical studies, is also evident. Probiotic microorganisms can be found in commercial products in a wide range of forms including powder, tablets or incorporated into liquid or solid food matrices. Milk and dairy products are suitable vehicles for the delivery of probiotics into the human body. Apart from well-established dairy-based probiotic foods including yogurt and yogurt-type beverages, in recent years some dairy products supplemented or enhanced with postbiotics and paraprobiotics are gaining popularity. The incorporation of next-generation probiotics in probiotic beverage formulations has also attracted the attention of researchers. The current state-of-the art for the utilization of next-generation probiotics, postbiotics and paraprobiotics in dairy-based probiotic beverages is the main focus of this review. Conventional milk-, whey- and buttermilk-based probiotic beverages are also covered.
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Affiliation(s)
- Şevval Taşkoparan
- Ankara University Faculty of Agriculture Department of Dairy Technology, Diskapi, Ankara, Turkey.
| | - Canan Altınay
- Ankara University Faculty of Agriculture Department of Dairy Technology, Diskapi, Ankara, Turkey.
| | - H Barbaros Özer
- Ankara University Faculty of Agriculture Department of Dairy Technology, Diskapi, Ankara, Turkey.
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Alamdar N, Farivar S, Baghaei K, Hamidieh AA, Soltaninejad H, Aghdaei HA, Zali MR, Saltanatpour Z. Effect of Pioglitazone and Cetuximab on Colon Cancer Stem-like Cell (CCSLCs) Properties. Curr Stem Cell Res Ther 2025; 20:83-90. [PMID: 38303523 DOI: 10.2174/011574888x283318240118111822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 12/26/2023] [Accepted: 12/29/2023] [Indexed: 02/03/2024]
Abstract
BACKGROUND One of the main reasons for cancer resistance to chemotherapy is the presence of cancer stem cells (CSCs) in cancer tissues. It is also believed that CSCs are the unique originators of all tumor cells. On the other hand, the Epithelial-Mesenchymal Transition pathway (EMT) can act as the main agent of metastasis. Therefore, it is possible that targeting CSCs as well as the EMT pathway could help in cancer therapy. Considering that CSCs constitute only a small percentage of the total tumor mass, enrichment before study is necessary. In our previous study, CSCs were enriched in the human colon cancer cell line HT29 by induction of EMT. These CSC-enriched HT29 cells with mesenchymal morphology were named "HT29-shE". In the present study, these cells were used to investigate the effect of Pioglitazone (Pio) and Cetuximab (Cet) in order to find CSC and EMT targeting agents. METHODS The viability and IC50 rate of cells treated with different concentrations of Pio and Cet were evaluated using the MTT test. EMT and CSC markers and cell morphology were assessed in Pio and Cet treated and untreated HT29-shE cells using flow cytometry, realtime PCR, immunocytochemistry, and microscopic monitoring. RESULTS The findings showed that Pio and Cet at concentrations of 250 μM and 40 μg/ml, respectively, decrease cell viability by 50%. Also, they were able to reduce the expression of CSC markers (CD133 and CD44) in the CSC enriched HT29 cell line. Furthermore, Pio and Cet could efficiently reduce the expression of vimentin as a mesenchymal marker and significantly upregulate the expression of E-cadherin as an epidermal marker of EMT and its reverse mesenchymal- toepithelial transition (MET). In addition, the mesenchymal morphology of HT29-shE changed into epithelial morphology after Cet treatment. CONCLUSION Pio and Cet could inhibit EMT and reduce CSC markers in the EMT induced/CSC enriched cell line. We expect that focus on finding EMT/CSC-targeting agents like these drugs can be helpful for cancer treatment.
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Affiliation(s)
- Nasim Alamdar
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Shirin Farivar
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Kaveh Baghaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorder Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Ali Hamidieh
- Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
- Stem Cell and Regenerative Medicine Innovation Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Soltaninejad
- Department of Stem Cells Technology and Tissue Regeneration, Faculty of Interdisciplinary Science and Technologies, Tarbiat Modares University, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorder Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zohreh Saltanatpour
- Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Sepehr A, Miri ST, Aghamohammad S, Rahimirad N, Milani M, Pourshafie MR, Rohani M. Health benefits, antimicrobial activities, and potential applications of probiotics: A review. Medicine (Baltimore) 2024; 103:e32412. [PMID: 39969286 PMCID: PMC11688011 DOI: 10.1097/md.0000000000032412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 12/02/2022] [Indexed: 02/20/2025] Open
Abstract
Gut microbiota and its metabolic activities can influence the physiology and pathology of the human body. It is well established that alterations in the balance of living microbiota can contribute to various health problems, such as inflammatory bowel disease and autoimmune disorders. Probiotics administered in sufficient quantities as functional food ingredients provide health benefits to hosts. They help to maintain the stability and composition of the gut microbiota and provide resistance to infection by pathogens. The most important probiotic bacteria are Lactobacillus spp. and Bifidobacteria spp., which protect the intestine through various mechanisms such as the production of organic acids and bacteriocins. Scientific and clinical research has demonstrated that probiotics play a role in modulating immune response and preventing cancer and chronic inflammatory diseases, especially in the gastrointestinal tract. This article summarizes the potential health benefits, antimicrobial activities, and purposes for which probiotics can be used as functional foods to improve human health.
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Affiliation(s)
- Amin Sepehr
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Seyedeh Tina Miri
- Department of Microbiology, Islamic Azad University Science and Research Branch, Tehran, Iran
| | | | - Nazanin Rahimirad
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mahnaz Milani
- Department of Microbiology, Islamic Azad University Science and Research Branch, Tehran, Iran
| | | | - Mahdi Rohani
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
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Sudaarsan ASK, Ghosh AR. Appraisal of postbiotics in cancer therapy. Front Pharmacol 2024; 15:1436021. [PMID: 39372197 PMCID: PMC11449718 DOI: 10.3389/fphar.2024.1436021] [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: 05/21/2024] [Accepted: 09/05/2024] [Indexed: 10/08/2024] Open
Abstract
Cancer remains a multifactorial disease with an increased mortality rate around the world for the past several decades. Despite advancements in treatment strategies, lower survival rates, drug-associated side effects, and drug resistance create a need for novel anticancer agents. Ample evidence shows that imbalances in the gut microbiota are associated with the formation of cancer and its progression. Altering the gut microbiota via probiotics and their metabolites has gained attention among the research community as an alternative therapy to treat cancer. Probiotics exhibit health benefits as well as modulate the immunological and cellular responses in the host. Apart from probiotics, their secreted products like bacteriocins, exopolysaccharides, short-chain fatty acids, conjugated linoleic acid, peptidoglycan, and other metabolites are found to possess anticancer activity. The beneficiary role of these postbiotic compounds is widely studied for characterizing their mechanism and mode of action that reduces cancer growth. The present review mainly focuses on the postbiotic components that are employed against cancer with their reported mechanism of action. It also describes recent research works carried out so far with specific strain and anticancer activity of derived compounds both in vitro and in vivo, validating that the probiotic approach would pave an alternative way to reduce the burden of cancer.
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Dobreva L, Atanasova N, Donchev P, Krumova E, Abrashev R, Karakirova Y, Mladenova R, Tolchkov V, Ralchev N, Dishliyska V, Danova S. Candidate-Probiotic Lactobacilli and Their Postbiotics as Health-Benefit Promoters. Microorganisms 2024; 12:1910. [PMID: 39338583 PMCID: PMC11434380 DOI: 10.3390/microorganisms12091910] [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: 08/28/2024] [Revised: 09/17/2024] [Accepted: 09/17/2024] [Indexed: 09/30/2024] Open
Abstract
Lactobacillus species are widely recognized for their probiotic potential, focusing on their mechanisms of health benefits and protection. Here we conducted an in vitro investigation of the probiotic potential with a role in microbiome homeostasis of four strains: Lactiplantibacillus plantarum L6 and F53, Ligilactobacillus salivarius 1, and Lactobacillus helveticus 611. A broad spectrum of antibacterial and antifungal activity was determined. The strain-specific inhibition of Staphylococcus aureus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, and saprophytic/toxigenic fungi makes them promising as protective cultures. DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid) measurements showed that tested samples had strain-specific capacity for scavenging of radicals. The molecular base for the antioxidant potential of two lyophilized forms of active strains was investigated by electron paramagnetic resonance spectroscopy. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, with fractions of the most active postbiotics obtained by SEC-FPLC (fast protein liquid chromatography) analysis, showed a wide variety of effects on the growth of a K562 myeloid leukemia cell line. The IC50 (half-maximal inhibitory concentration) of L. salivarius 1 was determined to be 46.15 mg/mL. The proven in vitro functionality of the selected lactobacilli make them suitable for development of target probiotics with specific beneficial effects expected in vivo. Further investigations on produced postbiotics and safety have to be completed before they can be considered as scientifically proven probiotic strains.
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Affiliation(s)
- Lili Dobreva
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
| | - Nikoleta Atanasova
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
| | - Petar Donchev
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
| | - Ekaterina Krumova
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
| | - Radoslav Abrashev
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
| | - Yordanka Karakirova
- Institute of Catalysis, Bulgarian Academy of Sciences, 11 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
| | - Ralitsa Mladenova
- Institute of Catalysis, Bulgarian Academy of Sciences, 11 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
| | - Vladimir Tolchkov
- National Center of Infectious and Parasitic Diseases, Yanko Sakuzov Blvd 26, 1504 Sofia, Bulgaria
| | - Nikola Ralchev
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
| | - Vladislava Dishliyska
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
| | - Svetla Danova
- The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria
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Kuru-Yaşar R, Üstün-Aytekin Ö. The Crucial Roles of Diet, Microbiota, and Postbiotics in Colorectal Cancer. Curr Nutr Rep 2024; 13:126-151. [PMID: 38483752 PMCID: PMC11133122 DOI: 10.1007/s13668-024-00525-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/25/2024] [Indexed: 05/30/2024]
Abstract
PURPOSE OF REVIEW Colorectal cancer is the second deadliest cancer in the world, and its prevalence has been increasing alarmingly in recent years. After researchers discovered the existence of dysbiosis in colorectal cancer, they considered the use of probiotics in the treatment of colorectal cancer. However, for various reasons, including the low safety profile of probiotics in susceptible and immunocompromised patient5s, and the risk of developing antibiotic resistance, researchers have shifted their focus to non-living cells, their components, and metabolites. This review aims to comprehensively evaluate the literature on the effects of diet, microbiota, and postbiotics on colorectal cancer and the future of postbiotics. RECENT FINDINGS The link between diet, gut microbiota, and colorectal cancer has been established primarily as a relationship rather than a cause-effect relationship. The gut microbiota can convert gastrointestinal tract and dietary factors into either onco-metabolites or tumor suppressor metabolites. There is serious dysbiosis in the microbiota in colorectal cancer. Postbiotics appear to be promising agents in the prevention and treatment of colorectal cancer. It has been shown that various postbiotics can selectively induce apoptosis in CRC, inhibit cell proliferation, growth, invasion, and migration, modulate the immune system, suppress carcinogenic signaling pathways, maintain intestinal epithelial integrity, and have a synergistic effect with chemotherapy drugs. However, it is also reported that some postbiotics are ineffective and may be risky in terms of safety profile in some patients. Many issues need to be researched about postbiotics. Large-scale, randomized, double-blind clinical studies are needed.
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Affiliation(s)
- Rüya Kuru-Yaşar
- Department of Nutrition and Dietetics, Hamidiye Faculty of Health Sciences, University of Health Sciences, 34668, Istanbul, Türkiye
| | - Özlem Üstün-Aytekin
- Department of Nutrition and Dietetics, Hamidiye Faculty of Health Sciences, University of Health Sciences, 34668, Istanbul, Türkiye.
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Khani N, Abedi Soleimani R, Chadorshabi S, Moutab BP, Milani PG, Rad AH. Postbiotics as candidates in biofilm inhibition in food industries. Lett Appl Microbiol 2024; 77:ovad069. [PMID: 37309029 DOI: 10.1093/lambio/ovad069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 05/28/2023] [Accepted: 06/09/2023] [Indexed: 06/14/2023]
Abstract
Food-borne pathogen-related biofilms in food processing environments pose significant risks to human health. To ensure human and environmental safety, natural substances with anti-microbial properties and generally recognized as safe (GRAS) status are the future disinfectants of the food industry. The use of postbiotics in food products is gaining attention due to their many benefits. Postbiotics are soluble substances produced by probiotics or released after their lysis, such as bacteriocins, biosurfactants (BSs), and exopolysaccharides (EPS). Postbiotics have drawn attention because of their clear chemical structure, safety dose parameters, long shelf life, and the content of various signaling molecules, which may have anti-biofilm and antibacterial activities. The main mechanisms of postbiotics to combat biofilm contain suppression of twitching motility, disturbing quorum sensing (QS), and reduction of virulence factors. However, there are obstacles to using these compounds in the food matrix because some factors (temperature and pH) can limit the anti-biofilm impact of postbiotics. Therefore, by using encapsulation or application of these compounds in packaging films, the effect of interfering factors can be eliminated. This review summarizes the concept and safety of postbiotics, focusing on their antibiofilm effect, as well as discussing the encapsulation of postbiotics and their application in packaging films.
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Affiliation(s)
- Nader Khani
- Student Research Committee, Tabriz University of Medical Sciences, 33366581 Tabriz, Iran
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, 33366581 Tabriz, Iran
| | - Roya Abedi Soleimani
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, 33366581 Tabriz, Iran
| | - Sara Chadorshabi
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, 33366581 Tabriz, Iran
| | - Bahareh Pouragha Moutab
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, 33366581 Tabriz, Iran
| | - Payam Gonbari Milani
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, 33366581 Tabriz, Iran
| | - Aziz Homayouni Rad
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, 33366581 Tabriz, Iran
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10
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Jastrząb R, Tomecki R, Jurkiewicz A, Graczyk D, Szczepankowska AK, Mytych J, Wolman D, Siedlecki P. The strain-dependent cytostatic activity of Lactococcus lactis on CRC cell lines is mediated through the release of arginine deiminase. Microb Cell Fact 2024; 23:82. [PMID: 38481270 PMCID: PMC10938756 DOI: 10.1186/s12934-024-02345-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 02/20/2024] [Indexed: 03/17/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, posing a serious public health challenge that necessitates the development of new therapeutics, therapies, and prevention methods. Among the various therapeutic approaches, interventions involving lactic acid bacteria (LAB) as probiotics and postbiotics have emerged as promising candidates for treating and preventing CRC. While human-isolated LAB strains are considered highly favorable, those sourced from environmental reservoirs such as dairy and fermented foods are also being recognized as potential sources for future therapeutics. RESULTS In this study, we present a novel and therapeutically promising strain, Lactococcus lactis ssp. lactis Lc4, isolated from dairy sources. Lc4 demonstrated the ability to release the cytostatic agent - arginine deiminase (ADI) - into the post-cultivation supernatant when cultured under conditions mimicking the human gut environment. Released arginine deiminase was able to significantly reduce the growth of HT-29 and HCT116 cells due to the depletion of arginine, which led to decreased levels of c-Myc, reduced phosphorylation of p70-S6 kinase, and cell cycle arrest. The ADI release and cytostatic properties were strain-dependent, as was evident from comparison to other L. lactis ssp. lactis strains. CONCLUSION For the first time, we unveil the anti-proliferative properties of the L. lactis cell-free supernatant (CFS), which are independent of bacteriocins or other small molecules. We demonstrate that ADI, derived from a dairy-Generally Recognized As Safe (GRAS) strain of L. lactis, exhibits anti-proliferative activity on cell lines with different levels of argininosuccinate synthetase 1 (ASS1) expression. A unique feature of the Lc4 strain is also its capability to release ADI into the extracellular space. Taken together, we showcase L. lactis ADI and the Lc4 strain as promising, potential therapeutic agents with broad applicability.
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Affiliation(s)
- Rafał Jastrząb
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Adolfa Pawińskiego 5A, Warsaw, 02-106, Poland
- Olimp Laboratories, Pustynia 84F, Debica, 39-200, Poland
| | - Rafał Tomecki
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Adolfa Pawińskiego 5A, Warsaw, 02-106, Poland
- Faculty of Biology, University of Warsaw, Miecznikowa 1, Warsaw, 02-089, Poland
| | - Aneta Jurkiewicz
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Adolfa Pawińskiego 5A, Warsaw, 02-106, Poland
| | - Damian Graczyk
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Adolfa Pawińskiego 5A, Warsaw, 02-106, Poland
| | - Agnieszka K Szczepankowska
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Adolfa Pawińskiego 5A, Warsaw, 02-106, Poland
| | | | - Damian Wolman
- Olimp Laboratories, Pustynia 84F, Debica, 39-200, Poland
| | - Pawel Siedlecki
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Adolfa Pawińskiego 5A, Warsaw, 02-106, Poland.
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Roy R, Singh SK. The Microbiome Modulates the Immune System to Influence Cancer Therapy. Cancers (Basel) 2024; 16:779. [PMID: 38398170 PMCID: PMC10886470 DOI: 10.3390/cancers16040779] [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: 01/22/2024] [Revised: 02/08/2024] [Accepted: 02/08/2024] [Indexed: 02/25/2024] Open
Abstract
The gut microbiota composition can affect the tumor microenvironment and its interaction with the immune system, thereby having implications for treatment predictions. This article reviews the studies available to better understand how the gut microbiome helps the immune system fight cancer. To describe this fact, different mechanisms and approaches utilizing probiotics to improve advancements in cancer treatment will be discussed. Moreover, not only calorie intake but also the variety and quality of diet can influence cancer patients' immunotherapy treatment because dietary patterns can impair immunological activities either by stimulating or suppressing innate and adaptive immunity. Therefore, it is interesting and critical to understand gut microbiome composition as a biomarker to predict cancer immunotherapy outcomes and responses. Here, more emphasis will be given to the recent development in immunotherapies utilizing microbiota to improve cancer therapies, which is beneficial for cancer patients.
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Affiliation(s)
- Ruchi Roy
- UICentre for Drug Discovery, The University of Illinois, Chicago, IL 60612, USA
| | - Sunil Kumar Singh
- Department of Surgery, Division of Surgical Oncology, The University of Illinois at Chicago, Chicago, IL 60612, USA
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Akkulak M, Evin E, Durukan O, Celebioglu HU, Adali O. Modulation of Caco-2 Colon Cancer Cell Viability and CYP2W1 Gene Expression by Hesperidin-treated Lacticaseibacillus rhamnosus GG (LGG) Cell-free Supernatants. Anticancer Agents Med Chem 2024; 24:372-378. [PMID: 38058098 DOI: 10.2174/0118715206271514231124111026] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 10/24/2023] [Accepted: 10/30/2023] [Indexed: 12/08/2023]
Abstract
BACKGROUND AND OBJECTIVE Ensuring colon homeostasis is of significant influence on colon cancer and delicate balance is maintained by a healthy human gut microbiota. Probiotics can modulate the diversity of the gut microbiome and prevent colon cancer. Metabolites/byproducts generated by microbial metabolism significantly impact the healthy colonic environment. Hesperidin is a polyphenolic plant compound well known for its anticancer properties. However, low bioavailability of hesperidin after digestion impedes its effectiveness. CYP2W1 is a newly discovered oncofetal gene with an unknown function. CYP2W1 gene expression peaks during embryonic development and is suddenly silenced immediately after birth. Only in the case of some types of cancer, particularly colorectal and hepatocellular carcinomas, this gene is reactivated and its expression is correlated with the severity of the disease. This study aimed to investigate the effects of hesperidin-treated Lacticaseibacillus rhamnosus GG (LGG) cell-free supernatants on CaCo2 colon cancer cell viability and CYP2W1 gene expression. METHODS Alamar Blue cell viability assay was used to investigate the cytotoxic effect of cell-free supernatant of LGG grown in the presence of hesperidin on CaCo2 cells. To observe the effect of cell-free supernatants of LGG on the expression of CYP2W1 gene, qRT-PCR was performed. RESULTS Five times diluted hesperidin treated cell-free supernatant (CFS) concentration considerably reduced CaCo2 colon cancer cell viability. Furthermore, CYP2W1 gene expression was similarly reduced following CFS treatments and nearly silenced under probiotic bacteria CFS treatment. CONCLUSION The CYP2W1 gene expression was strongly reduced by cell-free supernatants derived from LGG culture, with or without hesperidin. This suggests that the suppression may be due to bacterial byproducts rather than hesperidin. Therefore, the CYP2W1 gene in the case of deregulation of these metabolites may cause CYP2W1-related colon cancer cell proliferation.
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Affiliation(s)
- Merve Akkulak
- Department of Biological Sciences, Faculty of Science, Middle East Technical University, Ankara, 06800, Turkey
| | - Emre Evin
- Department of Biological Sciences, Faculty of Science, Middle East Technical University, Ankara, 06800, Turkey
| | - Ozlem Durukan
- Department of Biological Sciences, Faculty of Science, Middle East Technical University, Ankara, 06800, Turkey
| | - Hasan Ufuk Celebioglu
- Department of Biotechnology, Faculty of Science, Bartin University, Bartin, 74100, Turkey
| | - Orhan Adali
- Department of Biological Sciences, Faculty of Science, Middle East Technical University, Ankara, 06800, Turkey
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13
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Deng X, Yang J, Zhang Y, Chen X, Wang C, Suo H, Song J. An Update on the Pivotal Roles of Probiotics, Their Components, and Metabolites in Preventing Colon Cancer. Foods 2023; 12:3706. [PMID: 37835359 PMCID: PMC10572180 DOI: 10.3390/foods12193706] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/01/2023] [Accepted: 10/08/2023] [Indexed: 10/15/2023] Open
Abstract
Diet, lifestyle, and gut microbiota composition are key risk factors for the progression of colon cancer. Probiotics are living microorganisms that can offer health benefits to the parasitifer when ingested in competent quantities. Several in vivo, in vitro, and clinical studies have demonstrated that probiotics can prevent and mitigate the development of colon cancer. The anti-colon cancer mechanisms of probiotics include the suppression of cell proliferation and the promotion of cancer cell apoptosis, immunomodulation, the modulation of intestinal microorganisms and their metabolism, strengthening the intestinal barrier, and antioxidant effects. This article describes the pathogenesis of colon cancer and the available therapeutic options. In addition, this paper reviews the mechanisms by which probiotics mitigate colon cancer as well as the mitigating effects of probiotic components and metabolites on colon cancer.
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Affiliation(s)
- Xue Deng
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Jing Yang
- Chongqing Engineering Research Center for Processing & Storage of Distinct Agricultural Products, Chongqing Technology and Business University, Chongqing 400067, China;
| | - Yu Zhang
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Xiaoyong Chen
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Chen Wang
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
| | - Huayi Suo
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
- National Citrus Engineering Research Center, Southwest University, Chongqing 400712, China
| | - Jiajia Song
- College of Food Science, Southwest University, Chongqing 400715, China; (X.D.); (Y.Z.); (X.C.); (C.W.); (H.S.)
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14
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Shakhpazyan N, Mikhaleva L, Bedzhanyan A, Gioeva Z, Sadykhov N, Mikhalev A, Atiakshin D, Buchwalow I, Tiemann M, Orekhov A. Cellular and Molecular Mechanisms of the Tumor Stroma in Colorectal Cancer: Insights into Disease Progression and Therapeutic Targets. Biomedicines 2023; 11:2361. [PMID: 37760801 PMCID: PMC10525158 DOI: 10.3390/biomedicines11092361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Revised: 07/31/2023] [Accepted: 08/21/2023] [Indexed: 09/29/2023] Open
Abstract
Colorectal cancer (CRC) is a major health burden worldwide and is the third most common type of cancer. The early detection and diagnosis of CRC is critical to improve patient outcomes. This review explores the intricate interplay between the tumor microenvironment, stromal interactions, and the progression and metastasis of colorectal cancer. The review begins by assessing the gut microbiome's influence on CRC development, emphasizing its association with gut-associated lymphoid tissue (GALT). The role of the Wnt signaling pathway in CRC tumor stroma is scrutinized, elucidating its impact on disease progression. Tumor budding, its effect on tumor stroma, and the implications for patient prognosis are investigated. The review also identifies conserved oncogenic signatures (COS) within CRC stroma and explores their potential as therapeutic targets. Lastly, the seed and soil hypothesis is employed to contextualize metastasis, accentuating the significance of both tumor cells and the surrounding stroma in metastatic propensity. This review highlights the intricate interdependence between CRC cells and their microenvironment, providing valuable insights into prospective therapeutic approaches targeting tumor-stroma interactions.
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Affiliation(s)
- Nikolay Shakhpazyan
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (N.S.); (L.M.); (Z.G.); (N.S.); (A.O.)
| | - Liudmila Mikhaleva
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (N.S.); (L.M.); (Z.G.); (N.S.); (A.O.)
| | - Arkady Bedzhanyan
- Department of Abdominal Surgery and Oncology II (Coloproctology and Uro-Gynecology), Petrovsky National Research Center of Surgery, 119435 Moscow, Russia;
| | - Zarina Gioeva
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (N.S.); (L.M.); (Z.G.); (N.S.); (A.O.)
| | - Nikolay Sadykhov
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (N.S.); (L.M.); (Z.G.); (N.S.); (A.O.)
| | - Alexander Mikhalev
- Department of Hospital Surgery No. 2, Pirogov Russian National Research Medical University, 117997 Moscow, Russia;
| | - Dmitri Atiakshin
- Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples’ Friendship University of Russia, 117198 Moscow, Russia;
- Research Institute of Experimental Biology and Medicine, Burdenko Voronezh State Medical University, 394036 Voronezh, Russia
| | - Igor Buchwalow
- Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples’ Friendship University of Russia, 117198 Moscow, Russia;
- Institute for Hematopathology, 22547 Hamburg, Germany;
| | | | - Alexander Orekhov
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, 119435 Moscow, Russia; (N.S.); (L.M.); (Z.G.); (N.S.); (A.O.)
- Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia
- Institute for Atherosclerosis Research, 121096 Moscow, Russia
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15
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Thoda C, Touraki M. Probiotic-Derived Bioactive Compounds in Colorectal Cancer Treatment. Microorganisms 2023; 11:1898. [PMID: 37630458 PMCID: PMC10456921 DOI: 10.3390/microorganisms11081898] [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: 06/30/2023] [Revised: 07/14/2023] [Accepted: 07/24/2023] [Indexed: 08/27/2023] Open
Abstract
Colorectal cancer (CRC) is a multifactorial disease with increased morbidity and mortality rates globally. Despite advanced chemotherapeutic approaches for the treatment of CRC, low survival rates due to the regular occurrence of drug resistance and deleterious side effects render the need for alternative anticancer agents imperative. Accumulating evidence supports that gut microbiota imbalance precedes the establishment of carcinogenesis, subsequently contributing to cancer progression and response to anticancer therapy. Manipulation of the gut microbiota composition via the administration of probiotic-derived bioactive compounds has gradually attained the interest of scientific communities as a novel therapeutic strategy for CRC. These compounds encompass miscellaneous metabolic secreted products of probiotics, including bacteriocins, short-chain fatty acids (SCFAs), lactate, exopolysaccharides (EPSs), biosurfactants, and bacterial peptides, with profound anti-inflammatory and antiproliferative properties. This review provides a classification of postbiotic types and a comprehensive summary of the current state of research on their biological role against CRC. It also describes how their intricate interaction with the gut microbiota regulates the proper function of the intestinal barrier, thus eliminating gut dysbiosis and CRC development. Finally, it discusses the future perspectives in precision-medicine approaches as well as the challenges of their synthesis and optimization of administration in clinical studies.
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Affiliation(s)
| | - Maria Touraki
- Laboratory of General Biology, Department of Genetics, Development and Molecular Biology, School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, 54 124 Thessaloniki, Greece;
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16
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Akman PK, Kutlu G, Tornuk F. Development and characterization of a novel sodium alginate based active film supplemented with Lactiplantibacillus plantarum postbiotic. Int J Biol Macromol 2023:125240. [PMID: 37301346 DOI: 10.1016/j.ijbiomac.2023.125240] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 04/26/2023] [Accepted: 06/05/2023] [Indexed: 06/12/2023]
Abstract
In this study, sodium alginate based biodegradable films were prepared by the supplementation with postbiotics of Lactiplantibacillus plantarum subsp. plantarum (L. plantarum) W2 strain and the effect of probiotics (probiotic-SA film) and postbiotics (postbiotic-SA film) incorporation on physical, mechanical (tensile strength and elongation at break), barrier (oxygen and water vapor permeability), thermal and antimicrobial properties of the films were investigated. The pH, titratable acidity and brix of the postbiotic was 4.02, 1.24 % and 8.37, respectively while gallic acid, protocatechuic acid, myricetin and catechin were the major phenolic compounds. Mechanical and barrier properties of the alginate-based films were improved by probiotic or postbiotic supplementation while postbiotic showed a more pronounced (P < 0.05) effect. Thermal analysis showed that postbiotics supplementation increased thermal stability of the films. In FTIR spectra, the absorption peaks at 2341 and 2317 cm-1 for probiotic-SA and postbiotic-SA edible films confirmed the incorporation of probiotics/postbiotics of L. plantarum W2 strain. Postbiotic supplemented films showed strong antibacterial activity against gram-positive (L. monocytogenes, S. aureus and B. cereus) and one gram-negative bacterial strain (E. coli O157:H7) while probiotic incorporation did not add an antibacterial effect to the films. SEM images revealed that the supplementation of postbiotics provided a rougher and rigid film surface. Overall, this paper brought a new perspective for development of novel active biodegradable films by incorporation of postbiotics with improved performance.
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Affiliation(s)
- Perihan Kubra Akman
- Yildiz Technical University, Chemical and Metallurgical Engineering Faculty, Food Engineering Department, Davutpasa Campus, 34210 Istanbul, Turkey
| | - Gozde Kutlu
- Yildiz Technical University, Chemical and Metallurgical Engineering Faculty, Food Engineering Department, Davutpasa Campus, 34210 Istanbul, Turkey
| | - Fatih Tornuk
- Yildiz Technical University, Chemical and Metallurgical Engineering Faculty, Food Engineering Department, Davutpasa Campus, 34210 Istanbul, Turkey.
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17
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Microbiota-Derived Natural Products Targeting Cancer Stem Cells: Inside the Gut Pharma Factory. Int J Mol Sci 2023; 24:ijms24054997. [PMID: 36902427 PMCID: PMC10003410 DOI: 10.3390/ijms24054997] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/28/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
Cancer stem cells (CSCs) have drawn much attention as important tumour-initiating cells that may also be crucial for recurrence after chemotherapy. Although the activity of CSCs in various forms of cancer is complex and yet to be fully elucidated, opportunities for therapies targeting CSCs exist. CSCs are molecularly distinct from bulk tumour cells, so they can be targeted by exploiting their signature molecular pathways. Inhibiting stemness has the potential to reduce the risk posed by CSCs by limiting or eliminating their capacity for tumorigenesis, proliferation, metastasis, and recurrence. Here, we briefly described the role of CSCs in tumour biology, the mechanisms involved in CSC therapy resistance, and the role of the gut microbiota in cancer development and treatment, to then review and discuss the current advances in the discovery of microbiota-derived natural compounds targeting CSCs. Collectively, our overview suggests that dietary intervention, toward the production of those identified microbial metabolites capable of suppressing CSC properties, is a promising approach to support standard chemotherapy.
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18
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Noor S, Ali S, Riaz S, Sardar I, Farooq MA, Sajjad A. Chemopreventive role of probiotics against cancer: a comprehensive mechanistic review. Mol Biol Rep 2023; 50:799-814. [PMID: 36324027 DOI: 10.1007/s11033-022-08023-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 10/10/2022] [Indexed: 11/06/2022]
Abstract
Probiotics use different mechanisms such as intestinal barrier improvement, bacterial translocation and maintaining gut microbiota homeostasis to treat cancer. Probiotics' ability to induce apoptosis against tumor cells makes them more effective to treat cancer. Moreover, probiotics stimulate immune function through an immunomodulation mechanism that induces an anti-tumor effect. There are different strains of probiotics, but the most important ones are lactic acid bacteria (LAB) having antagonistic and anti-mutagenic activities. Live and dead probiotics have anti-inflammatory, anti-proliferative, anti-oxidant and anti-metastatic properties which are useful to fight against different diseases, especially cancer. The main focus of this article is to review the anti-cancerous properties of probiotics and their role in the reduction of different types of cancer. However, further investigations are in progress to improve the efficiency of probiotics in cancer treatment.
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Affiliation(s)
- Shehzeen Noor
- Applied Entomology and Medical Toxicology and Laboratory, Department of Zoology, Government College University, Lahore, Pakistan
| | - Shaukat Ali
- Applied Entomology and Medical Toxicology and Laboratory, Department of Zoology, Government College University, Lahore, Pakistan.
| | - Shumaila Riaz
- Applied Entomology and Medical Toxicology and Laboratory, Department of Zoology, Government College University, Lahore, Pakistan
| | - Iqra Sardar
- Applied Entomology and Medical Toxicology and Laboratory, Department of Zoology, Government College University, Lahore, Pakistan
| | - Muhammad Adeel Farooq
- Applied Entomology and Medical Toxicology and Laboratory, Department of Zoology, Government College University, Lahore, Pakistan
| | - Ayesha Sajjad
- Applied Entomology and Medical Toxicology and Laboratory, Department of Zoology, Government College University, Lahore, Pakistan
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19
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Kvakova M, Kamlarova A, Stofilova J, Benetinova V, Bertkova I. Probiotics and postbiotics in colorectal cancer: Prevention and complementary therapy. World J Gastroenterol 2022; 28:3370-3382. [PMID: 36158273 PMCID: PMC9346452 DOI: 10.3748/wjg.v28.i27.3370] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/22/2022] [Accepted: 06/16/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is a leading cause of human mortality worldwide. As conventional anticancer therapy not always being effective, there is growing interest in innovative “drug-free” cancer treatments or interventions that improve the efficacy of established therapy. CRC is associated with microbiome alterations, a process known as dysbiosis that involves depletion and/or enrichment of particular gut bacterial species and their metabolic functions. Supplementing patient treatment with traditional probiotics (with or without prebiotics), next-generation probiotics (NGP), or postbiotics represents a potentially effective and accessible complementary anticancer strategy by restoring gut microbiota composition and/or by signaling to the host. In this capacity, restoration of the gut microbiota in cancer patients can stabilize and enhance intestinal barrier function, as well as promote anticarcinogenic, anti-inflammatory, antimutagenic or other biologically important biochemical pathways that show high specificity towards tumor cells. Potential benefits of traditional probiotics, NGP, and postbiotics include modulating gut microbiota composition and function, as well as the host inflammatory response. Their application in CRC prevention is highlighted in this review, where we consider supportive in vitro, animal, and clinical studies. Based on emerging research, NGP and postbiotics hold promise in establishing innovative treatments for CRC by conferring physiological functions via the production of dominant natural products and metabolites that provide new host-microbiota signals to combat CRC. Although favorable results have been reported, further investigations focusing on strain and dose specificity are required to ensure the efficacy and safety of traditional probiotics, NGP, and postbiotics in CRC prevention and treatment.
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Affiliation(s)
- Monika Kvakova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Safarik University in Kosice, Kosice 04011, Slovakia
| | - Anna Kamlarova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Safarik University in Kosice, Kosice 04011, Slovakia
| | - Jana Stofilova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Safarik University in Kosice, Kosice 04011, Slovakia
| | - Veronika Benetinova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Safarik University in Kosice, Kosice 04011, Slovakia
| | - Izabela Bertkova
- Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, P.J. Safarik University in Kosice, Kosice 04011, Slovakia
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20
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Lactiplantibacillus plantarum inhibits colon cancer cell proliferation as function of its butyrogenic capability. Biomed Pharmacother 2022; 149:112755. [PMID: 35276466 DOI: 10.1016/j.biopha.2022.112755] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 02/21/2022] [Accepted: 02/23/2022] [Indexed: 11/21/2022] Open
Abstract
Lactobacilli have been shown to inhibit or suppress cancer cell growth through the release of strain-specific bioactive metabolites and their inclusion in functional foods could exert a health promoting activity on human health. Herein, we examined the antiproliferative activity of the Lactiplantibacillus plantarum strains S2T10D and O2T60C, which have been previously shown to exert different butyrogenic activities. Human HT-29 cells were employed as an in vitro colon cancer model and both bacterial strains were found to inhibit their growth. However, the strain S2T10D showed a greater antiproliferative activity which, interestingly, was correlated to its butyrogenic capability. Noteworthy, for the non-butyrogenic strain O2T60C, the growth inhibitory capability was rather limited. Furthermore, both the butyrate-containing supernatant of S2T10D and glucose-deprived cell culture medium supplemented with the same concentration of butyrate found in S2T10D supernatant, induced a pH-independent cancer cell growth inhibition accompanied by downregulation of cyclin D1 at mRNA level. The downregulation of cyclin D1 gene expression was accompanied by cell cycle arrest in G2/M phase and decrease of cyclin B1 and D1 protein levels. This in vitro study underlines the impact of Lpb. plantarum in the growth inhibition of cancer cells, and proposes butyrate-mediated cell cycle regulation as a potential involved mechanism. Since the production of butyric acid in Lpb. plantarum has been proven strain-dependent and differentially boosted by specific prebiotic compounds, our results open future research paths to determine whether this metabolic activity could be modulated in vivo by enhancing this antiproliferative effects on cancer cells.
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21
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Szemitko M, Golubinska-Szemitko E, Warakomski M, Falkowski A. Evaluation of CRC-Metastatic Hepatic Lesion Chemoembolization with Irinotecan-Loaded Microspheres, According to the Site of Embolization. J Pers Med 2022; 12:414. [PMID: 35330414 PMCID: PMC8953829 DOI: 10.3390/jpm12030414] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 02/16/2022] [Accepted: 03/01/2022] [Indexed: 02/01/2023] Open
Abstract
With the chemembolization of colorectal-cancer (CRC)-metastatic hepatic lesions by irinotecan-loaded microspheres, most researchers recommend slow embolizate delivery at the lobar-artery level to the entire liver parenchyma without obtaining visible stasis. An association has been reported between postoperatively visible embolizate stasis and lesion response to treatment. Possibly, in some cases, more selective administration might give greater benefit, particularly with previous systemic chemotherapy failure. Objective: Treatment response evaluation after chemoembolization of CRC-metastatic liver lesions with irinotecan-loaded microspheres, according to a hepatic-artery branch level of administration. Patients and methods: The analysis included 54 patients (24 females, 30 males) with large (median diameter > 5 cm) CRC-metastatic liver lesions, who underwent 196 chemoembolization procedures (mean 3.63 per patient) with irinotecan (100 mg)-loaded microspheres. Patients were divided into two groups according to initial embolizate-administration branch level: Group A (n = 26): at the segmental or subsegmental-vessel level; Group B (n = 28): at the lobar-branch level. Treatment response was assessed by computed-tomography (mRECIST criteria); overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan−Meier method and adverse effects were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE; version 5.0). Results: There were statistically significant differences in the occurrence of partial response (PR): higher in Group A (42.3%) than Group B (17.9%) (p = 0.039) and occurrence of stable disease (SD): lower (p = 0.025) in Group A (11.5%) than Group B (39.4%). However, occurrence of disease progression (PD) was similar: Group A: 42.3%; Group B: 42.9% (p = 0.93). Patients in Group A presented with more favorable PFS (p = 0.029) and OS (p = 0.039) than Group B. Median survival times: Group A: 15.2 months; Group B: 13.1 months. There was no significant difference in complication incidence between groups (Group A: seven complications; Group B: six complications; p = 0.863). Conclusion: Superselective chemoembolizate administration to vessels supplying large CRC-metastatic liver lesions gave better response to treatment and extended patient survival time, without significantly increasing complication risk.
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Affiliation(s)
- Marcin Szemitko
- Department of Interventional Radiology, Pomeranian Medical University, 70-111 Szczecin, Poland;
| | | | - Marcin Warakomski
- Department of General and Transplant Surgery, Pomeranian Medical University, 70-111 Szczecin, Poland;
| | - Aleksander Falkowski
- Department of Interventional Radiology, Pomeranian Medical University, 70-111 Szczecin, Poland;
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22
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Jampílek J, Kráľová K, Bella V. Probiotics and prebiotics in the prevention and management of human cancers (colon cancer, stomach cancer, breast cancer, and cervix cancer ). PROBIOTICS IN THE PREVENTION AND MANAGEMENT OF HUMAN DISEASES 2022:187-212. [DOI: 10.1016/b978-0-12-823733-5.00009-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Pawar K, Aranha C. Lactobacilli metabolites restore E-cadherin and suppress MMP9 in cervical cancer cells. Curr Res Toxicol 2022; 3:100088. [PMID: 36176311 PMCID: PMC9513734 DOI: 10.1016/j.crtox.2022.100088] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 08/18/2022] [Accepted: 09/20/2022] [Indexed: 11/18/2022] Open
Affiliation(s)
| | - Clara Aranha
- Corresponding author at: Department of Molecular Immunology and Microbiology, ICMR-National Institute for Research in Reproductive and Child Health, Parel, Mumbai 400102, India
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Mani-López E, Arrioja-Bretón D, López-Malo A. The impacts of antimicrobial and antifungal activity of cell-free supernatants from lactic acid bacteria in vitro and foods. Compr Rev Food Sci Food Saf 2021; 21:604-641. [PMID: 34907656 DOI: 10.1111/1541-4337.12872] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 11/03/2021] [Accepted: 11/04/2021] [Indexed: 01/12/2023]
Abstract
Lactic acid bacteria (LAB) are distinguished by their ability to produce lactic acid, among other interesting metabolites with antimicrobial activity. A cell-free supernatant (CFS) is a liquid containing the metabolites resulting from microbial growth and the residual nutrients of the medium used. CFS from LAB can have antimicrobial activity due to organic acids, fatty acids, and proteinaceous compounds, among other compounds. This review aims to summarize the information about CFS production, CFS composition, and the antimicrobial (antibacterial and antifungal) activity of CFS from LAB in vitro, on foods, and in active packaging. In addition, the mechanisms of action of CFS on cells, the stability of CFS during storage, CFS cytotoxicity, and the safety of CFS are reviewed. The main findings are that CFS's antibacterial and antifungal activity in vitro has been widely studied, particularly in members of the genus Lactobacillus. CFS has produced strong inhibition of bacteria and molds on foods when applied directly or in active packaging. In most studies, the compounds responsible for antimicrobial activity are identified. A few studies indicate that CFSs are stable for 1 to 5 months at temperatures ranging from 4 to 35°C. The cytotoxicity of CFS on human cells has not been well studied. However, the studies that have been performed reported no toxicity of CFS. Therefore, it is necessary to investigate novel growth mediums for CFS preparation that are compatible with food sensory properties. More studies into CFS stability and cytotoxic effects are also needed.
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Affiliation(s)
- Emma Mani-López
- Departamento de Ingeniería Química, Alimentos y Ambiental, Universidad de las Américas Puebla, Cholula, Puebla, Mexico
| | - Daniela Arrioja-Bretón
- Departamento de Ingeniería Química, Alimentos y Ambiental, Universidad de las Américas Puebla, Cholula, Puebla, Mexico
| | - Aurelio López-Malo
- Departamento de Ingeniería Química, Alimentos y Ambiental, Universidad de las Américas Puebla, Cholula, Puebla, Mexico
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25
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Wilson RM, Walker JM, Yin K. Different Concentrations of Lactobacillus acidophilus Cell Free Filtrate Have Differing Anti-Biofilm and Immunomodulatory Effects. Front Cell Infect Microbiol 2021; 11:737392. [PMID: 34589444 PMCID: PMC8473619 DOI: 10.3389/fcimb.2021.737392] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 08/24/2021] [Indexed: 01/14/2023] Open
Abstract
Probiotics such as various strains of Lactobacillaceae have been shown to have antimicrobial and immunomodulatory activity. In vitro studies have shown that Lactobacilli can decrease bacterial biofilm formation. Effects on immune cells have been unclear with most studies showing anti-inflammatory activity. The mechanism of effects has not been clearly elucidated. In these studies, we used different concentrations of live Lactobacillus acidophilus as well as cell free filtrate (CFF) derived from different concentrations of bacteria. Use of CFF is advantageous as a therapeutic because in vivo it can directly contact immune cells and its concentration is fixed. Both live cells and CFF inhibited Pseudomonas aeruginosa biofilm formation. Importantly, we show that high concentration CFF destroyed mature biofilm. This activity was not due to a lowered pH per se, as pH matched HCl did not remove mature biofilm. High concentration CFF totally inhibited P. aeruginosa growth and was bactericidal (>99.99%), but low concentration CFF was not bactericidal. To examine the immunomodulatory effects of L. acidophilus, we incubated THP-1 monocytes and derived macrophages with CFF and measured TNFα production. CFF did not significantly increase TNFα production in THP-1 monocytes. When cells were prestimulated with LPS, high concentration CFF increased TNFα production even further. In macrophages, high concentration CFF alone increased TNFα production but did not affect LPS prestimulated cells. In contrast, low concentration CFF decreased TNFα production in LPS prestimulated cells. To elucidate the possible mechanisms for these effects, we repeated the experiments using a NF-κB reporter THP-1 cell line. High concentration CFF increased NF-κB activity in monocytes and macrophages. In LPS prestimulated macrophages, only low concentration CFF reduced NF-κB activity. These results suggest that high concentration CFF alone induced NF-κB expression which could account partially for an increase in TNFα production. On the other hand, in macrophages, the lower non-bactericidal concentration of CFF reduced NF-κB expression and decreased TNFα production after LPS prestimulation. Taken together, the results provide evidence that different concentrations of L. acidophilus CFF possess varying bactericidal, anti-biofilm and immunomodulatory effects. This is important in vivo to evaluate the possible use of L. acidophilus CFF in different conditions.
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Affiliation(s)
- Rachael M Wilson
- Department of Cell Biology and Neuroscience, Rowan University - School of Osteopathic Medicine, Stratford, NJ, United States
| | - Jean M Walker
- Department of Cell Biology and Neuroscience, Rowan University - School of Osteopathic Medicine, Stratford, NJ, United States
| | - Kingsley Yin
- Department of Cell Biology and Neuroscience, Rowan University - School of Osteopathic Medicine, Stratford, NJ, United States
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26
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Johari B, Maghsood F, Madanchi H, Moradi M, Kadivar M. Investigating the anti-inflammatory effects of high molecular weight secretions from Limosilactobacillus reuteri PTCC 1655 on LPS-stimulated PMA-differentiated THP-1 cells. J Appl Microbiol 2021; 131:938-948. [PMID: 33377567 DOI: 10.1111/jam.14984] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 12/03/2020] [Accepted: 12/23/2020] [Indexed: 12/14/2022]
Abstract
AIMS This study was done to investigate the anti-inflammatory effects of high molecular weight secretions from Limosilactobacillus reuteri PTCC 1655 probiotic bacteria on lipopolysaccharide (LPS)-stimulated phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells. METHODS AND RESULTS After culturing the bacterium, the crude cell-free supernatant was fractionated on the basis of molecular weights using ultrafiltration. Also, a heat-killed and sonicated fraction was obtained from the biomass of the bacterial culture. All fractions were used to measure their anti-inflammatory effects on PMA-differentiated THP-1 cells following LPS stimulation by quantifying various cellular markers of inflammation. The results demonstrated that various L. reuteri PTCC 1655-derived fractions, especially the >100 kDa supernatant fraction decreased some of the inflammatory cytokines and mediators, including tumour necrosis factor-α, interleukin-1, nitric oxide, cyclooxygenase-2, matrix metalloproteinase-9 and interleukin-6, which are critical for the pathogenesis of some inflammatory diseases. CONCLUSION It is concluded that the L. reuteri PTCC 1655-derived high molecular weight fractions significantly reduce inflammation and therefore could be appropriate candidates for future medical studies. SIGNIFICANCE AND IMPACT OF THE STUDY Providing new insights about the significance of L. reuteri PTCC 1655-derived extracts and their potential to modulate inflammation.
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Affiliation(s)
- B Johari
- Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.,Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - F Maghsood
- Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran.,Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - H Madanchi
- Department of Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.,Drug Design and Bioinformatics Unit, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - M Moradi
- Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.,Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
| | - M Kadivar
- Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran
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27
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Moradi M, Kousheh SA, Almasi H, Alizadeh A, Guimarães JT, Yılmaz N, Lotfi A. Postbiotics produced by lactic acid bacteria: The next frontier in food safety. Compr Rev Food Sci Food Saf 2020; 19:3390-3415. [PMID: 33337065 DOI: 10.1111/1541-4337.12613] [Citation(s) in RCA: 134] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 07/04/2020] [Accepted: 07/16/2020] [Indexed: 12/18/2022]
Abstract
There are many critical challenges in the use of primary and secondary cultures and their biological compounds in food commodities. An alternative is the application of postbiotics from the starter and protective lactic acid bacteria (LAB). The concept of postbiotics is relatively new and there is still not a recognized definition for this term. The word "postbiotics" is currently used to refer to bioactive compounds, which did not fit to the traditional definitions of probiotics, prebiotics, and paraprobiotics. Therefore, the postbiotics may be presently defined as bioactive soluble factors (products or metabolic byproducts), produced by some food-grade microorganisms during the growth and fermentation in complex microbiological culture (in this case named cell-free supernatant), food, or gut, which exert some benefits to the food or the consumer. Many LAB are considered probiotic and their postbiotic compounds present similar or additional health benefits to the consumer; however, this review aimed to address the most recent applications of the postbiotics with food safety purposes. The potential applications of postbiotics in food biopreservation, food packaging, and biofilm control were reviewed. The current uses of postbiotics in the reduction and biodegradation of some food safety-related chemical contaminants (e.g., biogenic amines) were considered. We also discussed the safety aspects, the obstacles, and future perspectives of using postbiotics in the food industry. This work will open up new insights for food applications of postbiotics prepared from LAB.
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Affiliation(s)
- Mehran Moradi
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Seyedeh Alaleh Kousheh
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Hadi Almasi
- Department of Food Science and Technology, Faculty of Agriculture, Urmia University, Urmia, Iran
| | - Arash Alizadeh
- Division of Pharmacology and Toxicology, Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Jonas T Guimarães
- Department of Food Technology, Faculty of Veterinary Medicine, Federal Fluminense University (UFF), Niterói, Brazil
| | - Nurten Yılmaz
- Department of Animal Science, Faculty of Agriculture, Cukurova University, Adana, Turkey
| | - Anita Lotfi
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
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28
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Postbiotics and paraprobiotics: From concepts to applications. Food Res Int 2020; 136:109502. [PMID: 32846581 DOI: 10.1016/j.foodres.2020.109502] [Citation(s) in RCA: 165] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 06/22/2020] [Accepted: 06/24/2020] [Indexed: 02/07/2023]
Abstract
In recent years, new probiotic-related concepts such as postbiotics and paraprobiotics have been used to describe non-viable microorganisms or bacterial-free extracts that may provide benefits to the host by offering bioactivities additional to probiotics. However, several aspects related to these postbiotics and paraprobiotics bioactivities remain unexplored or are poorly understood. Therefore, the aim of this work is to provide an overview of the general aspects and emerging trends of postbiotics and paraprobiotics, such as conceptualization of terms, production, characterization, bioactivities, health-promoting effects, bioengineering approaches, and applications. In vitro and in vivo studies have demonstrated that some postbiotics and paraprobiotics exhibit bioactivities such as anti-inflammatory, immunomodulatory, anti-proliferative, antioxidant, and antimicrobial. These bioactivities could be involved in health-promoting effects observed in human and clinical trials, but despite the scientific evidence available, the mechanisms of action and the signaling pathways involved have not been fully elucidated. Nevertheless, paraprobiotics and postbiotics possess valuable potential for the development of biotechnological products with functional ingredients for the nutraceutical industry.
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