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Kumar V, Bahuguna A, Kumar S, Kim M. Xylooligosaccharides mediated gut microbiome modulation: prebiotics to postbiotics. Crit Rev Biotechnol 2025:1-19. [PMID: 40098333 DOI: 10.1080/07388551.2025.2460852] [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: 08/27/2024] [Revised: 11/12/2024] [Accepted: 01/05/2025] [Indexed: 03/19/2025]
Abstract
An increasing trend toward harnessing nutraceuticals as food supplements rather than pharmaceuticals as curative and preventive agents against various ailments has been observed. Owing to their health benefits, prebiotics have received notable attention from the pharmaceutical and food industries. Among the different prebiotic oligosaccharides, xylooligosaccharides (XOS) exhibited a remarkable capacity to stimulate the growth of the gut microbiota and benefit individuals with metabolic abnormalities. Additionally, XOS can be produced from various renewable agricultural wastes, which supports their economic feasibility for use as prebiotics at the industrial level. This review explains gut microbiome modulation based on in vivo, in vitro, and clinical findings. Gut microbiome modulation leads to the production of postbiotics that stimulate various beneficial health effects. The current review entails the mechanisms of different health-promoting activities mediated by XOS, including immunomodulation and anticancer effects. Additionally, the concept of converting prebiotics to synbiotics using XOS has been established for nutraceutical applications. Synbiotics based on XOS and probiotics may be good alternatives to nutraceuticals for improving human health.
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Affiliation(s)
- Vishal Kumar
- Department of Food Science and Technology, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, Republic of Korea
| | - Ashutosh Bahuguna
- Department of Food Science and Technology, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, Republic of Korea
| | - Subhash Kumar
- Department of Food Science and Technology, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, Republic of Korea
- Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, Republic of Korea
| | - Myunghee Kim
- Department of Food Science and Technology, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, Republic of Korea
- Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Gyeongsangbuk-do, Republic of Korea
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Asqardokht-Aliabadi A, Sarabi-Aghdam V, Homayouni-Rad A, Hosseinzadeh N. Postbiotics in the Bakery Products: Applications and Nutritional Values. Probiotics Antimicrob Proteins 2025; 17:292-314. [PMID: 39066881 DOI: 10.1007/s12602-024-10327-y] [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] [Accepted: 07/13/2024] [Indexed: 07/30/2024]
Abstract
In recent years, the consumption of postbiotics has gained significant attention due to their potential health benefits. However, their application in the bakery industry remains underutilized. This review focuses on recent advances in the use of postbiotics, specifically the metabolites of lactic acid bacteria, in bakery products. We provide a concise overview of the multifaceted benefits of postbiotics, including their role as natural antioxidants, antimicrobials, and preservatives, and their potential to enhance product quality, extend shelf-life, and contribute to consumer welfare. This review combines information from various sources to provide a comprehensive update on recent advances in the role of postbiotics in bakery products, subsequently discussing the concept of sourdough as a leavening agent and its role in improving the nutritional profile of bakery products. We highlighted the positive effects of postbiotics on bakery items, such as improved texture, flavor, and shelf life, as well as their potential to contribute to overall health through their antioxidant properties and their impact on gut health. Overall, this review emphasizes the promising potential of postbiotics to revolutionize the bakery industry and promote healthier and more sustainable food options. The integration of postbiotics into bakery products represents a promising frontier and offers innovative possibilities to increase product quality, reduce food waste, and improve consumer health. Further research into refining techniques to incorporate postbiotics into bakery products is essential for advancing the health benefits and eco-friendly nature of these vital food items.
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Affiliation(s)
- Abolfazl Asqardokht-Aliabadi
- Department of Food Science and Technology, Faculty of Agricultural Engineering, Sari Agricultural Sciences and Natural Resources University, Sari, Iran
| | - Vahideh Sarabi-Aghdam
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aziz Homayouni-Rad
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Negin Hosseinzadeh
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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Bingöl FG, Ağagündüz D, Budán F. Probiotic Bacterium-Derived p40, p75, and HM0539 Proteins as Novel Postbiotics and Gut-Associated Immune System (GAIS) Modulation: Postbiotic-Gut-Health Axis. Microorganisms 2024; 13:23. [PMID: 39858791 PMCID: PMC11767761 DOI: 10.3390/microorganisms13010023] [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: 12/08/2024] [Revised: 12/22/2024] [Accepted: 12/23/2024] [Indexed: 01/27/2025] Open
Abstract
It is known that probiotics have direct and indirect effects on many systems in the body, especially the gastrointestinal system. Interest in using probiotic strain-derived cell components and metabolites has also increased as a result of the significant benefits of probiotics. Although many terminologies and definitions are used for these components and metabolites, the International Scientific Association of Probiotics and Prebiotics (ISAPP) recommended the use of the term postbiotic in 2021, which is defined as "a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". Postbiotics are bioactive metabolites such as organic acids, peptides/proteins, cell wall components, functional enzymes, short-chain fatty acids, vitamins, and phenols. These molecules mediate many positive effects such as immunomodulatory, antimicrobial, and antioxidant effects. These positive effects on maintaining health have enabled the identification of many new postbiotic proteins such as p40, p75, and HM0539. In this review, the postbiotic proteins p40, p75, and HM0539 derived from lactobacilli and their functional effects are systematically summarized. The p40 protein, in particular, has been shown to support gut barrier activity and reduce inflammation, potentially through mechanisms involving epidermal growth factor receptor-dependent signaling. Additionally, p40 and p75 proteins exhibit protective effects on intestinal epithelial tight junctions, suggesting their therapeutic potential in preventing intestinal damage and diseases such as colitis. HM0539 enhances intestinal barrier integrity, exhibits antiinflammatory properties, and protects against bacterial infection, suggesting its possible as a therapeutic for inflammatory bowel disease. This review may contribute to future studies on the therapeutic use of p40, p75, and HM0539 postbiotic proteins in inflammatory gastrointestinal system diseases.
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Affiliation(s)
- Feray Gençer Bingöl
- Department of Nutrition and Dietetics, Faculty of Health Science, Burdur Mehmet Akif Ersoy University, 15200 Burdur, Türkiye;
| | - Duygu Ağagündüz
- Department of Nutrition and Dietetics, Faculty of Health Science, Gazi University, 06490 Ankara, Türkiye;
| | - Ferenc Budán
- Institute of Physiology, Medical School, University of Pécs, H-7624 Pécs, Hungary
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Devi MB, Bhattacharya A, Kumar A, Singh CT, Das S, Sarma HK, Mukherjee AK, Khan MR. Potential probiotic Lactiplantibacillus plantarum strains alleviate TNF-α by regulating ADAM17 protein and ameliorate gut integrity through tight junction protein expression in in vitro model. Cell Commun Signal 2024; 22:520. [PMID: 39468700 PMCID: PMC11514838 DOI: 10.1186/s12964-024-01900-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 10/19/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Lactiplantibacillus species are extensively studied for their ability to regulate host immune responses and functional therapeutic potentials. Nevertheless, there is a lack of understanding on the mechanisms of interactions with the hosts during immunoregulatory activities. METHODS Two Lactiplantibacillus plantarum strains MKMB01 and MKMB02 were tested for probiotic potential following Indian Council of Medical Research (ICMR) guidelines. Human colorectal adenocarcinoma cells such as HT-29, caco-2, and human monocytic cell THP-1 were also used to study the potential of MKMB01 and MKMB02 in regulating the host immune response when challenged with enteric pathogen Salmonella enterica typhimurium. Cells were pre-treated with MKMB01 and MKMB02 for 4 h and then stimulated with Salmonella. qRT-PCR and ELISA were used to analyze the genes and protein expression. Confocal microscopy and field emission scanning electron microscopy (FESEM) were used to visualize the effects. An Agilent Seahorse XF analyzer was used to determine real-time mitochondrial functioning. RESULTS Both probiotic strains could defend against Salmonella by maintaining gut integrity via expressing tight junction proteins (TJPs), MUC-2, and toll-like receptors (TLRs) negative regulators such as single Ig IL-1-related receptor (SIGIRR), toll-interacting protein (Tollip), interleukin-1 receptor-associated kinase (IRAK)-M, A20, and anti-inflammatory transforming growth factor-β and interleukin-10. Both strains also downregulated the expression of pro-inflammatory cytokines/chemokines interleukin-1β, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor-alpha (TNF-α), interleukin 6, and nitric oxide (NO). Moreover, TNF-α sheddase protein, a disintegrin and metalloproteinase domain 17 (ADAM17), and its regulator iRhom2 were downregulated by both strains. Moreover, the bacteria also ameliorated Salmonella-induced mitochondrial dysfunction by restoring bioenergetic profiles, such as non-mitochondrial respiration, spare respiratory capacity (SRC), basal respiration, adenosine triphosphate (ATP) production, and maximal respiration. CONCLUSIONS MKMB01 and MKMB02 can reduce pathogen-induced gut-associated disorders and therefore should be further explored for their probiotic potential.
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Affiliation(s)
- M Bidyarani Devi
- Division of Life Sciences, Institute of Advanced Study in Science and Technology (IASST), Guwahati, 781035, Assam, India
- Department of Biotechnology, Gauhati University, Guwahati, 781014, Assam, India
| | - Anupam Bhattacharya
- Division of Life Sciences, Institute of Advanced Study in Science and Technology (IASST), Guwahati, 781035, Assam, India
| | - Arun Kumar
- Division of Life Sciences, Institute of Advanced Study in Science and Technology (IASST), Guwahati, 781035, Assam, India
| | - Chingtham Thanil Singh
- Division of Life Sciences, Institute of Advanced Study in Science and Technology (IASST), Guwahati, 781035, Assam, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Santanu Das
- Division of Life Sciences, Institute of Advanced Study in Science and Technology (IASST), Guwahati, 781035, Assam, India
| | - Hridip Kumar Sarma
- Department of Biotechnology, Gauhati University, Guwahati, 781014, Assam, India
| | - Ashis K Mukherjee
- Division of Life Sciences, Institute of Advanced Study in Science and Technology (IASST), Guwahati, 781035, Assam, India
- Microbial Biotechnology and Protein Research laboratory, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, 784028, Assam, India
| | - Mojibur R Khan
- Division of Life Sciences, Institute of Advanced Study in Science and Technology (IASST), Guwahati, 781035, Assam, India.
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5
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Zhong Y, Liu Z, Wang Y, Cai S, Qiao Z, Hu X, Wang T, Yi J. Preventive Methods for Colorectal Cancer Through Dietary Interventions: A Focus on Gut Microbiota Modulation. FOOD REVIEWS INTERNATIONAL 2024:1-29. [DOI: 10.1080/87559129.2024.2414908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
- Yujie Zhong
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, China
- Yunnan Key Laboratory for Plateau Food Advanced Manufacturing, Kunming University of Science and Technology, Kunming, China
- International Green Food Processing Research and Development Center of Kunming City, Kunming University of Science and Technology, Kunming, China
| | - Zhijia Liu
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, China
- Yunnan Key Laboratory for Plateau Food Advanced Manufacturing, Kunming University of Science and Technology, Kunming, China
- International Green Food Processing Research and Development Center of Kunming City, Kunming University of Science and Technology, Kunming, China
| | - Yanfei Wang
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, China
- Yunnan Key Laboratory for Plateau Food Advanced Manufacturing, Kunming University of Science and Technology, Kunming, China
- International Green Food Processing Research and Development Center of Kunming City, Kunming University of Science and Technology, Kunming, China
| | - Shengbao Cai
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, China
- Yunnan Key Laboratory for Plateau Food Advanced Manufacturing, Kunming University of Science and Technology, Kunming, China
- International Green Food Processing Research and Development Center of Kunming City, Kunming University of Science and Technology, Kunming, China
| | - Zhu Qiao
- School of Biological and Food Processing Engineering, Huanghuai University, Zhumadian, Henan Province, China
| | - Xiaosong Hu
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, China
- Yunnan Key Laboratory for Plateau Food Advanced Manufacturing, Kunming University of Science and Technology, Kunming, China
- International Green Food Processing Research and Development Center of Kunming City, Kunming University of Science and Technology, Kunming, China
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Tao Wang
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, China
- Yunnan Key Laboratory for Plateau Food Advanced Manufacturing, Kunming University of Science and Technology, Kunming, China
- International Green Food Processing Research and Development Center of Kunming City, Kunming University of Science and Technology, Kunming, China
| | - Junjie Yi
- Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, China
- Yunnan Key Laboratory for Plateau Food Advanced Manufacturing, Kunming University of Science and Technology, Kunming, China
- International Green Food Processing Research and Development Center of Kunming City, Kunming University of Science and Technology, Kunming, China
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6
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Calvigioni M, Mazzantini D, Celandroni F, Vozzi G, Ghelardi E. Cultivating complexity: Advancements in establishing in vitro models for the mucus-adhering gut microbiota. Microb Biotechnol 2024; 17:e70036. [PMID: 39435730 PMCID: PMC11494453 DOI: 10.1111/1751-7915.70036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 10/02/2024] [Indexed: 10/23/2024] Open
Abstract
A healthy mucus is essential for maintaining intestinal homeostasis and overall well-being. In recent years, extensive research focused on understanding the intricate interactions between mucus and the gut microbiota. Mucus-adhering bacteria play crucial roles in preserving barrier integrity, epithelial permeability and mucus architecture, as well as in the colonization resistance against pathogens. Unravelling the significance of these microorganisms in human health and disease is challenging, primarily because most of the studies on the human gut microbiota rely on faecal samples, which do not fully represent the microecological complexity found in the intestinal mucosa. This review discusses novel strategies to specifically target and evaluate the mucosal microbiota, such as culturomics applied to mucosal biopsies or brushings, intestinal organoids and artificial in vitro models incorporating mucus.
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Affiliation(s)
- Marco Calvigioni
- Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
| | - Diletta Mazzantini
- Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
| | - Francesco Celandroni
- Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
| | - Giovanni Vozzi
- Department of Information BioengineeringUniversity of PisaPisaItaly
- Research Center Enrico PiaggioUniversity of PisaPisaItaly
| | - Emilia Ghelardi
- Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
- Research Center Nutraceuticals and Food for Health – NutrafoodUniversity of PisaPisaItaly
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7
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Brasino DSK, Speese SD, Schilling K, Schutt CE, Barton MC. A Linkable, Polycarbonate Gut Microbiome-Distal Tumor Chip Platform for Interrogating Cancer Promoting Mechanisms. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2309220. [PMID: 39023197 PMCID: PMC11425222 DOI: 10.1002/advs.202309220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 05/31/2024] [Indexed: 07/20/2024]
Abstract
Gut microbiome composition is tied to diseases ranging from arthritis to cancer to depression. However, mechanisms of action are poorly understood, limiting development of relevant therapeutics. Organ-on-chip platforms, which model minimal functional units of tissues and can tightly control communication between them, are ideal platforms to study these relationships. Many gut microbiome models are published to date but devices are typically fabricated using oxygen permeable polydimethylsiloxane, requiring interventions to support anaerobic bacteria. To address this challenge, a platform is developed where the chips are fabricated entirely from gas-impermeable polycarbonate without tapes or gaskets. These chips replicate polarized villus-like structures of the native tissue. Further, they enable co-cultures of commensal anaerobic bacteria Blautia coccoides on the surface of gut epithelia for two days within a standard incubator. Another complication of commonly used materials in organ-on-chip devices is high ad-/absorption, limiting applications in high-resolution microscopy and biomolecule interaction studies. For future communication studies between gut microbiota and distal tumors, an additional polycarbonate chip design is developed to support hydrogel-embedded tissue culture. These chips enable high-resolution microscopy with all relevant processing done on-chip. Designed for facile linking, this platform will make a variety of mechanistic studies possible.
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Affiliation(s)
- Danielle S K Brasino
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97201, USA
| | - Sean D Speese
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97201, USA
| | - Kevin Schilling
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97201, USA
| | - Carolyn E Schutt
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97201, USA
- Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, 97201, USA
| | - Michelle C Barton
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97201, USA
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Leser T, Baker A. Molecular Mechanisms of Lacticaseibacillus rhamnosus, LGG ® Probiotic Function. Microorganisms 2024; 12:794. [PMID: 38674738 PMCID: PMC11051730 DOI: 10.3390/microorganisms12040794] [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: 02/26/2024] [Revised: 04/10/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024] Open
Abstract
To advance probiotic research, a comprehensive understanding of bacterial interactions with human physiology at the molecular and cellular levels is fundamental. Lacticaseibacillus rhamnosus LGG® is a bacterial strain that has long been recognized for its beneficial effects on human health. Probiotic effector molecules derived from LGG®, including secreted proteins, surface-anchored proteins, polysaccharides, and lipoteichoic acids, which interact with host physiological processes have been identified. In vitro and animal studies have revealed that specific LGG® effector molecules stimulate epithelial cell survival, preserve intestinal barrier integrity, reduce oxidative stress, mitigate excessive mucosal inflammation, enhance IgA secretion, and provide long-term protection through epigenetic imprinting. Pili on the cell surface of LGG® promote adhesion to the intestinal mucosa and ensure close contact to host cells. Extracellular vesicles produced by LGG® recapitulate many of these effects through their cargo of effector molecules. Collectively, the effector molecules of LGG® exert a significant influence on both the gut mucosa and immune system, which promotes intestinal homeostasis and immune tolerance.
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Affiliation(s)
- Thomas Leser
- Future Labs, Human Health Biosolutions, Novonesis, Kogle Alle 6, 2970 Hoersholm, Denmark;
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9
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Domínguez-Díaz C, Avila-Arrezola KE, Rodríguez JA, del-Toro-Arreola S, Delgado-Rizo V, Fafutis-Morris M. Recombinant p40 Protein Promotes Expression of Occludin in HaCaT Keratinocytes: A Brief Communication. Microorganisms 2023; 11:2913. [PMID: 38138057 PMCID: PMC10745755 DOI: 10.3390/microorganisms11122913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 11/27/2023] [Accepted: 11/30/2023] [Indexed: 12/24/2023] Open
Abstract
The ability of epithelial barriers to perform as the first defense line against external damage derives from tight junctions, protein complexes that block microorganisms through the paracellular space. Indeed, disturbances of barrier permeability caused by bacterial metabolites and other inflammatory stimuli are the consequence of changes in protein expression in these complexes. Postbiotics, molecules derived from bacteria with beneficial effects on the host, improve barrier function through the activation of survival pathways in epithelial cells. Lacticaseibacillus rhamnosus GG secretes the muramidase p40, which protects intestinal barriers through an EGFR-dependent pathway. In this work, we cloned, expressed, and purified the recombinant p40 protein from L. rhamnosus GR-1 to evaluate its effect on cell viability, cell cytotoxicity, TEER, and protein levels of tight junctions, as well as EGFR activation via Western blot on HaCaT keratinocytes subjected to LPS. We found a novel mutation at residue 368 that does not change the structure of p40. Our protein also reduces the LPS-induced increase in cell cytotoxicity when it is added prior to this stimulus. Furthermore, although LPS did not cause changes in barrier function, p40 increased TEER and occludin expression in HaCaT, but unlike previous work with p40 from LGG, we found that recombinant p40 did not activate EGFR. This suggests that recombinant p40 enhances epithelial barrier function through distinct signaling pathways.
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Affiliation(s)
- Carolina Domínguez-Díaz
- Doctoral Program in Biomedical Sciences, Physiology Department, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico;
- Immunology and Dermatology Research Center (CIINDE), Zapopan 45190, Mexico;
| | | | - Jorge A. Rodríguez
- Department of Industrial Biotechnology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Zapopan 45019, Mexico;
| | - Susana del-Toro-Arreola
- Physiology Department, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico; (S.d.-T.-A.); (V.D.-R.)
| | - Vidal Delgado-Rizo
- Physiology Department, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico; (S.d.-T.-A.); (V.D.-R.)
| | - Mary Fafutis-Morris
- Immunology and Dermatology Research Center (CIINDE), Zapopan 45190, Mexico;
- Physiology Department, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico; (S.d.-T.-A.); (V.D.-R.)
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10
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Kaur H, Ali SA, Short SP, Williams CS, Goettel JA, Washington MK, Peek RM, Acra SA, Yan F. Identification of a functional peptide of a probiotic bacterium-derived protein for the sustained effect on preventing colitis. Gut Microbes 2023; 15:2264456. [PMID: 37815528 PMCID: PMC10566403 DOI: 10.1080/19490976.2023.2264456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 09/25/2023] [Indexed: 10/11/2023] Open
Abstract
Several probiotic-derived factors have been identified as effectors of probiotics for exerting beneficial effects on the host. However, there is a paucity of studies to elucidate mechanisms of their functions. p40, a secretory protein, is originally isolated from a probiotic bacterium, Lactobacillus rhamnosus GG. Thus, this study aimed to apply structure-functional analysis to define the functional peptide of p40 that modulates the epigenetic program in intestinal epithelial cells for sustained prevention of colitis. In silico analysis revealed that p40 is composed of a signal peptide (1-28 residues) followed by a coiled-coil domain with uncharacterized function on the N-terminus, a linker region, and a β-sheet domain with high homology to CHAP on the C-terminus. Based on the p40 three-dimensional structure model, two recombinant p40 peptides were generated, p40N120 (28-120 residues) and p40N180 (28-180 residues) that contain first two and first three coiled coils, respectively. Compared to full-length p40 (p40F) and p40N180, p40N120 showed similar or higher effects on up-regulating expression of Setd1b (encoding a methyltransferase), promoting mono- and trimethylation of histone 3 on lysine 4 (H3K4me1/3), and enhancing Tgfb gene expression and protein production that leads to SMAD2 phosphorylation in human colonoids and a mouse colonic epithelial cell line. Furthermore, supplementation with p40F and p40N120 in early life increased H3K4me1, Tgfb expression and differentiation of regulatory T cells (Tregs) in the colon, and mitigated disruption of epithelial barrier and inflammation induced by DSS in adult mice. This study reveals the structural feature of p40 and identifies a functional peptide of p40 that could maintain intestinal homeostasis.
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Affiliation(s)
- Harpreet Kaur
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Syed Azmal Ali
- Division of Proteomics of Stem Cell and Cancer, German Cancer Research Center, Heidelberg, Germany
| | - Sarah P. Short
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | | | - Jeremy A. Goettel
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA
| | - M. Kay Washington
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Richard M. Peek
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sari A. Acra
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Fang Yan
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA
- Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA
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11
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He J, Li H, Jia J, Liu Y, Zhang N, Wang R, Qu W, Liu Y, Jia L. Mechanisms by which the intestinal microbiota affects gastrointestinal tumours and therapeutic effects. MOLECULAR BIOMEDICINE 2023; 4:45. [PMID: 38032415 PMCID: PMC10689341 DOI: 10.1186/s43556-023-00157-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 11/08/2023] [Indexed: 12/01/2023] Open
Abstract
The intestinal microbiota is considered to be a forgotten organ in human health and disease. It maintains intestinal homeostasis through various complex mechanisms. A significant body of research has demonstrated notable differences in the gut microbiota of patients with gastrointestinal tumours compared to healthy individuals. Furthermore, the dysregulation of gut microbiota, metabolites produced by gut bacteria, and related signal pathways can partially explain the mechanisms underlying the occurrence and development of gastrointestinal tumours. Therefore, this article summarizes the latest research progress on the gut microbiota and gastrointestinal tumours. Firstly, we provide an overview of the composition and function of the intestinal microbiota and discuss the mechanisms by which the intestinal flora directly or indirectly affects the occurrence and development of gastrointestinal tumours by regulating the immune system, producing bacterial toxins, secreting metabolites. Secondly, we present a detailed analysis of the differences of intestinal microbiota and its pathogenic mechanisms in colorectal cancer, gastric cancer, hepatocellular carcinoma, etc. Lastly, in terms of treatment strategies, we discuss the effects of the intestinal microbiota on the efficacy and toxic side effects of chemotherapy and immunotherapy and address the role of probiotics, prebiotics, FMT and antibiotic in the treatment of gastrointestinal tumours. In summary, this article provides a comprehensive review of the pathogenic mechanisms of and treatment strategies pertaining to the intestinal microbiota in patients with gastrointestinal tumours. And provide a more comprehensive and precise scientific basis for the development of microbiota-based treatments for gastrointestinal tumours and the prevention of such tumours.
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Affiliation(s)
- Jikai He
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Haijun Li
- Department of Gastrointestinal Surgery, Inner Mongolia Autonomous Region People's Hospital, Hohhot, 010017, Inner Mongolia, China
| | - Jiaqi Jia
- Graduate School of Youjiang Medical University for Nationalities, No. 98 Chengcheng Road, Youjiang District, Baise City, 533000, China
| | - Yang Liu
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Ning Zhang
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Rumeng Wang
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China
| | - Wenhao Qu
- Graduate School of Youjiang Medical University for Nationalities, No. 98 Chengcheng Road, Youjiang District, Baise City, 533000, China
| | - Yanqi Liu
- Department of Gastroenterology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot City, 010050, Inner Mongolia, China.
| | - Lizhou Jia
- Central Laboratory, Bayannur Hospital, Bayannur, 015000, Inner Mongolia, China.
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12
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Pal P, Shastry RP. Exploring the complex role of gut microbiome in the development of precision medicine strategies for targeting microbial imbalance-induced colon cancer. Folia Microbiol (Praha) 2023; 68:691-701. [PMID: 37624549 DOI: 10.1007/s12223-023-01085-5] [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: 03/29/2023] [Accepted: 08/17/2023] [Indexed: 08/26/2023]
Abstract
The gut microbiome has been increasingly recognized as a key player in the development and progression of colon cancer. Alterations in the gut microbiota, known as dysbiosis, can lead to a variety of medical issues. Microbial adaptation through signals and small molecules can enhance pathogen colonization and modulate host immunity, significantly impacting disease progression. Quorum sensing peptides and molecules have been linked to the progression of colon cancer. Various interventions, such as fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics, have been used to reverse dysbiosis with mixed results and potential side effects. Thus, a personalized approach to treatment selection based on patient characteristics, such as individual gut microbiota manipulation, is necessary to prevent and treat diseases like colon cancer. With advances in metagenomic sequencing and other omics technologies, there has been a growing interest in developing precision medicine strategies for microbial imbalance-induced colon cancer. This review serves as a comprehensive synthesis of current knowledge on the gut microbiome involvement in colon cancer. By exploring the potential of utilizing the gut microbiome as a target for precision medicine, this review underscores the exciting opportunities that lie ahead. Although challenges exist, the integration of microbiome data into precision medicine approaches has the potential to revolutionize the management of colon cancer, providing patients with more personalized and effective treatment options.
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Affiliation(s)
- Pamela Pal
- Division of Microbiology and Biotechnology, Yenepoya (Deemed to Be University), Yenepoya Research Centre, University Road, Mangaluru-575018, India
| | - Rajesh P Shastry
- Division of Microbiology and Biotechnology, Yenepoya (Deemed to Be University), Yenepoya Research Centre, University Road, Mangaluru-575018, India.
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Stolfi C, Pacifico T, Monteleone G, Laudisi F. Impact of Western Diet and Ultra-Processed Food on the Intestinal Mucus Barrier. Biomedicines 2023; 11:2015. [PMID: 37509654 PMCID: PMC10377275 DOI: 10.3390/biomedicines11072015] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 06/19/2023] [Accepted: 07/15/2023] [Indexed: 07/30/2023] Open
Abstract
The intestinal epithelial barrier plays a key role in the absorption of nutrients and water, in the regulation of the interactions between luminal contents and the underlying immune cells, and in the defense against enteric pathogens. Additionally, the intestinal mucus layer provides further protection due to mucin secretion and maturation by goblet cells, thus representing a crucial player in maintaining intestinal homeostasis. However, environmental factors, such as dietary products, can disrupt this equilibrium, leading to the development of inflammatory intestinal disorders. In particular, ultra-processed food, which is broadly present in the Western diet and includes dietary components containing food additives and/or undergoing multiple industrial processes (such as dry heating cooking), was shown to negatively impact intestinal health. In this review, we summarize and discuss current knowledge on the impact of a Western diet and, in particular, ultra-processed food on the mucus barrier and goblet cell function, as well as potential therapeutic approaches to maintain and restore the mucus layer under pathological conditions.
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Affiliation(s)
- Carmine Stolfi
- Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Teresa Pacifico
- Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
| | - Giovanni Monteleone
- Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
- Gastroenterology Unit, Policlinico Universitario Tor Vergata, 00133 Rome, Italy
| | - Federica Laudisi
- Department of Systems Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy
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14
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Nakandalage R, Guan LL, Malmuthuge N. Microbial Interventions to Improve Neonatal Gut Health. Microorganisms 2023; 11:1328. [PMID: 37317302 DOI: 10.3390/microorganisms11051328] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 05/04/2023] [Accepted: 05/16/2023] [Indexed: 06/16/2023] Open
Abstract
The diverse pioneer microbial community colonizing the mammalian gastrointestinal tract is critical for the developing immune system. Gut microbial communities of neonates can be affected by various internal and external factors, resulting in microbial dysbiosis. Microbial dysbiosis during early life affects gut homeostasis by changing metabolic, physiological, and immunological status, which increases susceptibility to neonatal infections and long-term pathologies. Early life is crucial for the establishment of microbiota and the development of the host immune system. Therefore, it provides a window of opportunity to reverse microbial dysbiosis with a positive impact on host health. Recent attempts to use microbial interventions during early life have successfully reversed dysbiotic gut microbial communities in neonates. However, interventions with persistent effects on microbiota and host health are still limited. This review will critically discuss microbial interventions, modulatory mechanisms, their limitations, and gaps in knowledge to understand their roles in improving neonatal gut health.
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Affiliation(s)
- Ranga Nakandalage
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, Canada
- Lethbridge Research and Development Center, Agriculture Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada
| | - Le Luo Guan
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2P5, Canada
| | - Nilusha Malmuthuge
- Lethbridge Research and Development Center, Agriculture Agri-Food Canada, Lethbridge, AB T1J 4B1, Canada
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Wang R, Kuerman M, Cui Q, Tian X, Zhou Y, Yi H, Gong P, Lin K, Zhang Z, Liu T, Zhang L. Protective effects of Bifidobacterium bifidum FL-228.1 on dextran sulfate sodium-induced intestinal damage in mice. Eur J Nutr 2023; 62:1267-1280. [PMID: 36520190 DOI: 10.1007/s00394-022-03064-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 11/23/2022] [Indexed: 12/23/2022]
Abstract
PURPOSE Numerous studies have found that probiotics benefit the intestinal barrier. However, the prophylactic effects of probiotics on the intestinal barrier, i.e., if probiotics exert protective effects in healthy individuals to defend them against harmful elements, have seldomly been reported. The present study aimed to investigate the possible mechanisms of potential strains with the function of preventing intestinal barrier damage. METHODS This study investigated nine potential probiotic strains using in vitro and in vivo models on their intestinal barrier-protecting properties. Transcriptomic was then employed to decipher the underlying mechanisms of action of the strains. RESULTS The results showed that the strains, to varying degrees, regulated the ratio of interleukin (IL)-10 and IL-12 in peripheral blood mononuclear cells (PBMCs), increased the transepithelial electrical resistance (TEER) values, and decreased Caco-2 cell monolayers permeability. Correspondingly, the strains showed different prophylactic efficacies in protecting mice from dextran sulfate sodium (DSS)-induced intestinal barrier damage. Remarkably, Bifidobacterium bifidum FL-228.1 (FL-228.1) showed the best prophylactic efficacies in protecting mice from DSS-induced intestinal barrier damage. Further research suggested that FL-228.1 exerted its prophylactic effects by enhancing mucin 2 (Muc2) production and Claudin (Cldn)-4 in the colon. Furthermore, the transcriptomic and protein-protein interactions (PPI) analyses indicated that the inhibition of NLRP3 and the activation of PPARγ and TLR2 could be involved in protecting the intestinal barrier by FL-228.1. CONCLUSION Bifidobacterium bifidum FL-228.1 may be developed as a promising probiotic for the prevention of intestinal barrier damage via PPARγ/NLRP3/ TLR2 pathways by enhancing Muc2 and Cldn-4.
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Affiliation(s)
- Rui Wang
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China
| | - Malina Kuerman
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China
| | - Qingyu Cui
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China
| | - Xiaoying Tian
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China
| | - Yu Zhou
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China
| | - Huaxi Yi
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China
| | - Pimin Gong
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China
| | - Kai Lin
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China
| | - Zhe Zhang
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China
| | - Tongjie Liu
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China.
| | - Lanwei Zhang
- College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao, 266003, China.
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Liu Y, Yu Z, Zhu L, Ma S, Luo Y, Liang H, Liu Q, Chen J, Guli S, Chen X. Orchestration of MUC2 - The key regulatory target of gut barrier and homeostasis: A review. Int J Biol Macromol 2023; 236:123862. [PMID: 36870625 DOI: 10.1016/j.ijbiomac.2023.123862] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 02/22/2023] [Accepted: 02/24/2023] [Indexed: 03/06/2023]
Abstract
The gut mucosa of human is covered by mucus, functioning as a crucial defense line for the intestine against external stimuli and pathogens. Mucin2 (MUC2) is a subtype of secretory mucins generated by goblet cells and is the major macromolecular component of mucus. Currently, there is an increasing interest on the investigations of MUC2, noting that its function is far beyond a maintainer of the mucus barrier. Moreover, numerous gut diseases are associated with dysregulated MUC2 production. Appropriate production level of MUC2 and mucus contributes to gut barrier function and homeostasis. The production of MUC2 is regulated by a series of physiological processes, which are orchestrated by various bioactive molecules, signaling pathways and gut microbiota, etc., forming a complex regulatory network. Incorporating the latest findings, this review provided a comprehensive summary of MUC2, including its structure, significance and secretory process. Furthermore, we also summarized the molecular mechanisms of the regulation of MUC2 production aiming to provide developmental directions for future researches on MUC2, which can act as a potential prognostic indicator and targeted therapeutic manipulation for diseases. Collectively, we elucidated the micro-level mechanisms underlying MUC2-related phenotypes, hoping to offer some constructive guidance for intestinal and overall health of mankind.
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Affiliation(s)
- Yaxin Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Zihan Yu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Lanping Zhu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Shuang Ma
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Yang Luo
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Huixi Liang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Qinlingfei Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Jihua Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Sitan Guli
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China; Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China.
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Otte ML, Lama Tamang R, Papapanagiotou J, Ahmad R, Dhawan P, Singh AB. Mucosal healing and inflammatory bowel disease: Therapeutic implications and new targets. World J Gastroenterol 2023; 29:1157-1172. [PMID: 36926666 PMCID: PMC10011951 DOI: 10.3748/wjg.v29.i7.1157] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/16/2022] [Accepted: 02/14/2023] [Indexed: 02/21/2023] Open
Abstract
Mucosal healing (MH) is vital in maintaining homeostasis within the gut and protecting against injury and infections. Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair. However, when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results, particularly inflammatory bowel disease (IBD). Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions, with the mechanisms of regulation just beginning to be understood. Consequently, there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes, so tissue damage in the gastrointestinal tract of patients, even those in clinical remission, persists. With increased understanding of the molecular mechanisms of IBD and MH, tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response. In this review, we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.
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Affiliation(s)
- Megan Lynn Otte
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Raju Lama Tamang
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Julia Papapanagiotou
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Rizwan Ahmad
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Punita Dhawan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Amar B Singh
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, United States
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Pandey H, Tang DWT, Wong SH, Lal D. Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities. Cancers (Basel) 2023; 15:cancers15030866. [PMID: 36765824 PMCID: PMC9913759 DOI: 10.3390/cancers15030866] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 02/03/2023] Open
Abstract
Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide. While CRC is thought to be an interplay between genetic and environmental factors, several lines of evidence suggest the involvement of gut microbiota in promoting inflammation and tumor progression. Gut microbiota refer to the ~40 trillion microorganisms that inhabit the human gut. Advances in next-generation sequencing technologies and metagenomics have provided new insights into the gut microbial ecology and have helped in linking gut microbiota to CRC. Many studies carried out in humans and animal models have emphasized the role of certain gut bacteria, such as Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, in the onset and progression of CRC. Metagenomic studies have opened up new avenues for the application of gut microbiota in the diagnosis, prevention, and treatment of CRC. This review article summarizes the role of gut microbiota in CRC development and its use as a biomarker to predict the disease and its potential therapeutic applications.
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Affiliation(s)
- Himani Pandey
- Redcliffe Labs, Electronic City, Noida 201301, India
| | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore 308232, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- Correspondence: (S.H.W.); (D.L.)
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi 110007, India
- Correspondence: (S.H.W.); (D.L.)
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Schalich K, Rajagopala S, Das S, O’Connell R, Yan F. Intestinal epithelial cell-derived components regulate transcriptome of Lactobacillus rhamnosus GG. Front Microbiol 2023; 13:1051310. [PMID: 36687654 PMCID: PMC9846326 DOI: 10.3389/fmicb.2022.1051310] [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: 09/22/2022] [Accepted: 11/24/2022] [Indexed: 01/06/2023] Open
Abstract
Introduction Intestinal epithelial cells (IECs) provide the frontline responses to the gut microbiota for maintaining intestinal homeostasis. Our previous work revealed that IEC-derived components promote the beneficial effects of a commensal and probiotic bacterium, Lactobacillus rhamnosus GG (LGG). This study aimed to elucidate the regulatory effects of IEC-derived components on LGG at the molecular level. Methods Differential gene expression in LGG cultured with IEC-derived components at the timepoint between the exponential and stationary phase was studied by RNA sequencing and functional analysis. Results The transcriptomic profile of LGG cultured with IEC-derived components was significantly different from that of control LGG, with 231 genes were significantly upregulated and 235 genes significantly down regulated (FDR <0.05). The Clusters of Orthologous Groups (COGs) and Gene Ontology (GO) analysis demonstrated that the predominant genes enriched by IEC-derived components are involved in nutrient acquisition, including transporters for amino acids, metals, and sugars, biosynthesis of amino acids, and in the biosynthesis of cell membrane and cell wall, including biosynthesis of fatty acid and lipoteichoic acid. In addition, genes associated with cell division and translation are upregulated by IEC-derived components. The outcome of the increased transcription of these genes is supported by the result that IEC-derived components significantly promoted LGG growth. The main repressed genes are associated with the metabolism of amino acids, purines, carbohydrates, glycerophospholipid, and transcription, which may reflect regulation of metabolic mechanisms in response to the availability of nutrients in bacteria. Discussion These results provide mechanistic insight into the interactions between the gut microbiota and the host.
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Affiliation(s)
- Kasey Schalich
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Seesandra Rajagopala
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Suman Das
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States,Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Ryan O’Connell
- Department of Pathology, University of Utah, Salt Lake City, UT, United States
| | - Fang Yan
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States,Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United States,*Correspondence: Fang Yan,
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20
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Wang L, Yu KC, Hou YQ, Guo M, Yao F, Chen ZX. Gut microbiome in tumorigenesis and therapy of colorectal cancer. J Cell Physiol 2023; 238:94-108. [PMID: 36409765 DOI: 10.1002/jcp.30917] [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: 08/02/2022] [Revised: 11/09/2022] [Accepted: 11/09/2022] [Indexed: 11/22/2022]
Abstract
Colorectal cancer (CRC) is the malignant tumor with the highest incidence in the digestive system, and the gut microbiome plays a crucial role in CRC tumorigenesis and therapy. The gastrointestinal tract is the organ harboring most of the microbiota in humans. Changes in the gut microbiome in CRC patients suggest possible host-microbe interactions, thereby hinting the potential tumorigenesis, which provides new perspective for preventing, diagnosing, or treating CRC. In this review, we discuss the effects of gut microbiome dysbiosis on CRC, and reveal the mechanisms by which gut microbiome dysbiosis leads to CRC. Gut microbiome modulation with the aim to reverse the established gut microbial dysbiosis is a novel strategy for the prevention and treatment of CRC. In addition, this review summarizes that probiotic antagonize CRC tumorigenesis by protecting intestinal barrier function, inhibiting cancer cell proliferation, resisting oxidative stress, and enhancing host immunity. Finally, we highlight clinical applications of the gut microbiome, such as gut microbiome analysis-based biomarker screening and prediction, and microbe modulation-based CRC prevention, treatment enhancement, and treatment side effect reduction. This review provides the reference for the clinical application of gut microbiome in the prevention and treatment of CRC.
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Affiliation(s)
- Ling Wang
- Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, People's Republic of China
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
- Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen, People's Republic of China
| | - Ke-Chun Yu
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Yun-Qing Hou
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Min Guo
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Fan Yao
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
| | - Zhen-Xia Chen
- Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, People's Republic of China
- Hubei Hongshan Laboratory, College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, People's Republic of China
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Life Science and Technology, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, People's Republic of China
- Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Shenzhen, People's Republic of China
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Transcriptional responses of human intestinal epithelial HT-29 cells to spore-displayed p40 derived from Lacticaseibacillus rhamnosus GG. BMC Microbiol 2022; 22:316. [PMID: 36550414 PMCID: PMC9772600 DOI: 10.1186/s12866-022-02735-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 12/12/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUNDS The aims of this study were to construct spore-displayed p40, a Lacticaseibacillus rhamnosus GG-derived soluble protein, using spore surface display technology and to evaluate transcriptional responses in human intestinal epithelial cells. RESULTS p40 was displayed on the surface of Bacillus subtilis spores using spore coat protein CotG as an anchor protein. Effects of spore-displayed p40 (CotG-p40) on gene expression of intestinal epithelial cell line HT-29 were evaluated by transcriptome analysis using RNA-sequencing. As a result of differentially expressed gene (DEG) analysis, 81 genes were up-regulated and 82 genes were down-regulated in CotG-p40 stimulated cells than in unstimulated cells. Gene ontology enrichment analysis showed that CotG-p40 affected biological processes such as developmental process, metabolic process, cell surface receptor linked signaling pathway, and retinoic acid metabolic process. Gene-gene network analysis suggested that 10 DEGs (EREG, FOXF1, GLI2, PTGS2, SPP1, MMP19, TNFRSF1B, PTGER4, CLDN18, and ALDH1A3) activated by CotG-p40 were associated with probiotic action. CONCLUSIONS This study demonstrates the regulatory effects of CotG-p40 on proliferation and homeostasis of HT-29 cells. This study provided comprehensive insights into the transcriptional response of human intestinal epithelial cells stimulated by CotG-p40.
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Kang SJ, Jun JS, Hong KW. Transcriptome Analysis Reveals Immunomodulatory Effect of Spore-Displayed p75 on Human Intestinal Epithelial Caco-2 Cells. Int J Mol Sci 2022; 23:ijms232314519. [PMID: 36498846 PMCID: PMC9739243 DOI: 10.3390/ijms232314519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/19/2022] [Accepted: 11/20/2022] [Indexed: 11/23/2022] Open
Abstract
Lacticaseibacillus rhamnosus GG (LGG) can promote intestinal health by modulating the immune responses of the gastrointestinal tract. However, knowledge about the immunomodulatory action of LGG-derived soluble factors is limited. In our previous study, we have displayed LGG-derived p75 protein on the spore surface of Bacillus subtilis. The objective of this study was to determine the effect of spore-displayed p75 (CotG-p75) on immune system by investigating transcriptional response of Caco-2 cells stimulated by CotG-p75 through RNA-sequencing (RNA-seq). RNA-seq results showed that CotG-p75 mainly stimulated genes involved in biological processes, such as response to stimulus, immune regulation, and chemotaxis. KEGG pathway analysis suggested that many genes activated by CotG-p75 were involved in NF-ĸB signaling and chemokine signaling pathways. CotG-p75 increased cytokines and chemokines such as CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, CCL20, CCL22, and IL1B essential for the immune system. In particular, CotG-p75 increased the expression levels of NF-ĸB-related genes such as NFKBIA, TNFAIP3, BIRC3, NFKB2, and RELB involved in immune and inflammatory responses. This study provides genes and pathways involved in immune responses influenced by CotG-p75. These comprehensive transcriptome profiling could be used to elucidate the immunomodulatory action of CotG-p75.
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Efficacy of Selected Live Biotherapeutic Candidates to Inhibit the Interaction of an Adhesive-Invasive Escherichia coli Strain with Caco-2, HT29-MTX Cells and Their Co-Culture. Biomedicines 2022; 10:biomedicines10092245. [PMID: 36140346 PMCID: PMC9496071 DOI: 10.3390/biomedicines10092245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/06/2022] [Accepted: 09/07/2022] [Indexed: 11/17/2022] Open
Abstract
Adherent-invasive Escherichia coli (AIEC) has been implicated as a microbiological factor in the pathogenesis of inflammatory bowel disease (IBD). We evaluated the ability of six live biotherapeutic products (LBPs) to inhibit the interaction of an AIEC strain to three cell lines representing human gut epithelium. Co-inoculation of LBPs with AIEC showed a reduction in adhesion (up to 73%) and invasion of AIEC (up to 89%). Pre-inoculation of LBPs in HT-29-MTX and Caco-2 cells before challenging with AIEC further reduced the adhesion and invasion of the AIEC, with three LBPs showing significantly (p < 0.0001) higher efficiency in reducing the adhesion of AIEC. In co-inoculation experiments, the highest reduction in adhesion (73%) of AIEC was observed in HT-29-MTX cells, whereas the highest reduction in invasion (89%) was seen in HT-29-MTX and the co-culture of cells. Pre-inoculation of LBPs further reduced the invasion of AIEC with highest reduction (97%) observed in co-culture of cells. Our results indicated that whilst there were differences in the efficacy of LBPs, they all reduced interaction of AIEC with cell lines representing gut epithelium. Their efficiency was higher when they were pre-inoculated onto the cells, suggesting their potential as candidates for alleviating pathogenesis of AIEC in patients with IBD.
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Kaur H, Ali SA, Yan F. Interactions between the gut microbiota-derived functional factors and intestinal epithelial cells - implication in the microbiota-host mutualism. Front Immunol 2022; 13:1006081. [PMID: 36159834 PMCID: PMC9492984 DOI: 10.3389/fimmu.2022.1006081] [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: 07/28/2022] [Accepted: 08/23/2022] [Indexed: 12/13/2022] Open
Abstract
Mutual interactions between the gut microbiota and the host play essential roles in maintaining human health and providing a nutrient-rich environment for the gut microbial community. Intestinal epithelial cells (IECs) provide the frontline responses to the gut microbiota for maintaining intestinal homeostasis. Emerging evidence points to commensal bacterium-derived components as functional factors for the action of commensal bacteria, including protecting intestinal integrity and mitigating susceptibility of intestinal inflammation. Furthermore, IECs have been found to communicate with the gut commensal bacteria to shape the composition and function of the microbial community. This review will discuss the current understanding of the beneficial effects of functional factors secreted by commensal bacteria on IECs, with focus on soluble proteins, metabolites, and surface layer components, and highlight the impact of IECs on the commensal microbial profile. This knowledge provides a proof-of-concept model for understanding of mechanisms underlying the microbiota-host mutualism.
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Affiliation(s)
- Harpreet Kaur
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Syed Azmal Ali
- German Cancer Research Center, Division of Proteomics of Stem Cell and Cancer, Heidelberg, Germany
| | - Fang Yan
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States,Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, United States,*Correspondence: Fang Yan,
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25
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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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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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27
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Effects of Spore-Displayed p75 Protein from Lacticaseibacillus rhamnosus GG on the Transcriptional Response of HT-29 Cells. Microorganisms 2022; 10:microorganisms10071276. [PMID: 35888995 PMCID: PMC9323162 DOI: 10.3390/microorganisms10071276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/20/2022] [Accepted: 06/22/2022] [Indexed: 12/10/2022] Open
Abstract
A Lacticaseibacillus rhamnosus GG-derived protein, p75, is one of the key molecules exhibiting probiotic activity. However, the molecular mechanism and transcriptional response of p75 in human intestinal epithelial cells are not completely understood. To gain a deeper understanding of its potential probiotic action, this study investigated genome-wide responses of HT-29 cells to stimulation by spore-displayed p75 (CotG-p75) through a transcriptome analysis based on RNA sequencing. Analysis of RNA-seq data showed significant changes of gene expression in HT-29 cells stimulated by CotG-p75 compared to the control. A total of 189 up-regulated and 314 down-regulated genes was found as differentially expressed genes. Gene ontology enrichment analysis revealed that a large number of activated genes was involved in biological processes, such as epithelial cell differentiation, development, and regulation of cell proliferation. A gene–gene interaction network analysis showed that several DEGs, including AREG, EREG, HBEGF, EPGN, FASLG, GLI2, CDKN1A, FOSL1, MYC, SERPINE1, TNFSF10, BCL6, FLG, IVL, SPRR1A, SPRR1B, SPRR3, and MUC5AC, might play a critical role in these biological processes. RNA-seq results for selected genes were verified by reverse transcription-quantitative polymerase chain reaction. Overall, these results provide extensive knowledge about the transcriptional responses of HT-29 cells to stimulation by CotG-p75. This study showed that CotG-p75 can contribute to cell survival and epithelial development in human intestinal epithelial cells.
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Wu J, Zhou B, Pang X, Song X, Gu Y, Xie R, Liu T, Xu X, Wang B, Cao H. Clostridium butyricum, a butyrate-producing potential probiotic, alleviates experimental colitis through epidermal growth factor receptor activation. Food Funct 2022; 13:7046-7061. [PMID: 35678197 DOI: 10.1039/d2fo00478j] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Inflammatory bowel disease (IBD) is an idiopathic inflammatory bowel disease. Modulation of gut microbiota with dietary and nutritional targets is a feasible strategy for the prevention and treatment of IBD. In this study, we focused on Clostridium butyricum Prazmowski (CB), a butyrate-producing potential probiotic. We found that CB feeding decreased the disease activity index, colon inflammation/injury score and cell apoptosis in an experimental colitis mouse model, as well as elevated the level of SCFAs in cecal feces. CB could also balance the inflammatory cytokines, protect tight junctions, and increase the number of goblet cells and MUC2 production in mice, accompanied by EGFR signaling activation triggered by heparin-binding epidermal growth factor (HB-EGF) and amphiregulin (AREG). From the perspective of mechanism, the CB supernatant (CBS) stimulated EGFR activation in colon epithelial cell lines in concentration-dependent and time-dependent manners. CBS reduced the damage of tight junctions induced by H2O2, and inhibition of EGFR could suppress the protective effect of CBS. In conclusion, CB could protect the gut barrier and alleviate experimental colitis through the transactivation of EGFR signaling in intestinal epithelial cells induced by ligands (HB-EGF and AREG). This study identified the potential efficacy of CB as a preventive strategy for IBD and showed the broad prospect of CB as a food supplement.
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Affiliation(s)
- Jingyi Wu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Bingqian Zhou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Xiaoqi Pang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Xueli Song
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Yu Gu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Runxiang Xie
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Tianyu Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Xin Xu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.
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Mei L, Zhang D, Shao H, Hao Y, Zhang T, Zheng W, Ji Y, Ling P, Lu Y, Zhou Q. Injectable and Self-Healing Probiotics-Loaded Hydrogel for Promoting Superbacteria-Infected Wound Healing. ACS APPLIED MATERIALS & INTERFACES 2022; 14:20538-20550. [PMID: 35471815 DOI: 10.1021/acsami.1c23713] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Superbacteria-induced skin wound infections are huge health challenges, resulting in significant financial and medical costs due to notable morbidity and mortality worldwide. Probiotics are found in the skin and are effective in treating bacterial infection, moderating the microbial dysbiosis and inflammation induced by pathogens, regulating the immune system, as well as even promoting tissue repair. However, improving their colonization efficiency and viability remains a large obstacle for proper applications. Inspired by probiotic therapy and the natural extracellular matrix structure, hyaluronate-adipic dihydrazide/aldehyde-terminated Pluronic F127/fucoidan hydrogels loaded with Lactobacillus rhamnosus (HPF@L.rha) with unique (bio)physicochemical characteristics were developed through the dynamic Schiff-base reaction for superbacteria-infected trauma management. The developed HPF@L.rha exhibit a shortened gelation time, enhanced mechanical strength, and excellent self-healing and liquid-absorption abilities. Importantly, their anti-superbacteria (Pseudomonas aeruginosa) effect was greatly increased in a dose-dependent fashion. Additionally, in vitro evaluation shows that the prepared HPF@L.rha containing appropriate probiotic concentrations (less than 1 × 107 CFU/mL) possess satisfactory cytocompatibility and blood compatibility. Further, compared to the HPF hydrogel, in vivo the hydrogel combined with probiotics significantly inhibits P. aeruginosa infection and inflammation, promotes the formation of re-epithelialization and collagen, and thus accelerates full-thickness superbacteria-infected wound repair, which is comparable to commercial Prontosan gel formulation. This work suggests that the combination of biomimicking hydrogels and probiotic therapy displays the great potential to manage superbug-infected trauma.
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Affiliation(s)
- Li Mei
- Institute for Translational Medicine, Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China
- Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid, Tianjin 300038, China
- School of Stomatology, Qingdao University, Qingdao 266003, China
| | - Dongjie Zhang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
| | - Huarong Shao
- Key Laboratory of Biopharmaceuticals, Shandong Academy of Pharmaceutical Sciences, Jinan 250101, China
| | - Yuanping Hao
- Institute for Translational Medicine, Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China
| | - Ting Zhang
- Institute for Translational Medicine, Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China
- School of Stomatology, Qingdao University, Qingdao 266003, China
| | - Weiping Zheng
- Institute for Translational Medicine, Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China
- School of Stomatology, Qingdao University, Qingdao 266003, China
| | - Yanjing Ji
- Institute for Translational Medicine, Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China
- School of Stomatology, Qingdao University, Qingdao 266003, China
| | - Peixue Ling
- Key Laboratory of Biopharmaceuticals, Shandong Academy of Pharmaceutical Sciences, Jinan 250101, China
| | - Yun Lu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
| | - Qihui Zhou
- Institute for Translational Medicine, Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China
- Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid, Tianjin 300038, China
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Breugelmans T, Oosterlinck B, Arras W, Ceuleers H, De Man J, Hold GL, De Winter BY, Smet A. The role of mucins in gastrointestinal barrier function during health and disease. Lancet Gastroenterol Hepatol 2022; 7:455-471. [PMID: 35397245 DOI: 10.1016/s2468-1253(21)00431-3] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 11/05/2021] [Accepted: 11/08/2021] [Indexed: 12/23/2022]
Abstract
Mucins are the gatekeepers of the mucosal barrier of the gastrointestinal tract and are aberrantly expressed in various gastrointestinal pathologies, including pathogen infection, inflammation, and uncontrolled growth and spread of abnormal cells. Although several studies have emphasised the role of mucins in dysfunction of the gastrointestinal mucosal barrier, they are often still considered to be passive mediators of this barrier instead of regulators or modulators. In this Review, we discuss the interactions between mucins and gastrointestinal barrier function during health and disease. We will focus on the bidirectional relationship between mucins and the gut microbiota and will also address the molecular mechanisms involved in key cell signalling pathways, such as inflammation, cell interactions, and cell differentiation, proliferation, and survival. Additionally, we highlight the potential use of mucins in the diagnosis, follow-up, and treatment of gastrointestinal diseases, such as chronic inflammatory diseases and cancer.
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Affiliation(s)
- Tom Breugelmans
- Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium
| | - Baptiste Oosterlinck
- Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium
| | - Wout Arras
- Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium
| | - Hannah Ceuleers
- Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium
| | - Joris De Man
- Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium
| | - Georgina L Hold
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Benedicte Y De Winter
- Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium; Department of Gastroenterology and Hepatology, University Hospital of Antwerp, Antwerp, Belgium
| | - Annemieke Smet
- Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium.
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Nickel L, Sünderhauf A, Rawish E, Stölting I, Derer S, Thorns C, Matschl U, Othman A, Sina C, Raasch W. The AT1 Receptor Blocker Telmisartan Reduces Intestinal Mucus Thickness in Obese Mice. Front Pharmacol 2022; 13:815353. [PMID: 35431918 PMCID: PMC9009210 DOI: 10.3389/fphar.2022.815353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 03/07/2022] [Indexed: 11/13/2022] Open
Abstract
The angiotensin II (type 1) (AT1) receptor blocker telmisartan (TEL) is beneficial for the treatment of individuals suffering from metabolic syndrome. As we have shown that TEL has an impact on gut microbiota, we investigated here whether TEL influences gut barrier function. C57BL/6N mice were fed with chow or high-fat diet (HFD) and treated with vehicle or TEL (8 mg/kg/day). Mucus thickness was determined by immunohistochemistry. Periodic Acid-Schiff staining allowed the number of goblet cells to be counted. Using western blots, qPCR, and immunohistochemistry, factors related to mucus biosynthesis (Muc2, St6galnac), proliferation (Ki-67), or necroptosis (Rip3) were measured. The influence on cell viability was determined in vitro by using losartan, as the water solubility of TEL was too low for in vitro experiments. Upon HFD, mice developed obesity as well as leptin and insulin resistance, which were prevented by TEL. Mucus thickness upon HFD-feeding was diminished. Independent of feeding, TEL additionally reduced mucus thickness. Numbers of goblet cells were not affected by HFD-feeding and TEL. St6galnac expression was increased by TEL. Rip3 was increased in TEL-treated and HFD-fed mice, while Ki-67 decreased. Cell viability was diminished by using >1 mM losartan. The anti-obese effect of TEL was associated with a decrease in mucus thickness, which was likely not related to a lower expression of Muc2 and goblet cells. A decrease in Ki-67 and increase in Rip3 indicates lower cell proliferation and increased necroptosis upon TEL. However, direct cell toxic effects are ruled out, as in vivo concentrations are lower than 1 mM.
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Affiliation(s)
- Laura Nickel
- Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany
| | - Annika Sünderhauf
- Division of Nutritional Medicine, University Hospital Schleswig-Holstein, Lübeck, Germany
| | - Elias Rawish
- Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany
| | - Ines Stölting
- Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany
| | - Stefanie Derer
- Division of Nutritional Medicine, University Hospital Schleswig-Holstein, Lübeck, Germany
| | | | - Urte Matschl
- Department Virus Immunology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany
| | - Alaa Othman
- CBBM (Centre of Brain, Behaviour and Metabolism), University of Lübeck, Lübeck, Germany
- Institute for Clinical Chemistry, University Hospital Zürich, Zürich, Germany
| | - Christian Sina
- Division of Nutritional Medicine, University Hospital Schleswig-Holstein, Lübeck, Germany
| | - Walter Raasch
- Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany
- CBBM (Centre of Brain, Behaviour and Metabolism), University of Lübeck, Lübeck, Germany
- *Correspondence: Walter Raasch,
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The Role of Aeromonas-Goblet Cell Interactions in Melatonin-Mediated Improvements in Sleep Deprivation-Induced Colitis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:8133310. [PMID: 35355860 PMCID: PMC8958064 DOI: 10.1155/2022/8133310] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 01/26/2022] [Accepted: 02/17/2022] [Indexed: 11/18/2022]
Abstract
Background. Our previous studies demonstrated that melatonin could effectively ameliorate sleep deprivation- (SD-) caused oxidative stress-mediated gut microbiota disorder and colitis. The research further clarified the mechanism of melatonin in improving colitis from the perspective of the interaction between Aeromonas and goblet cells. Methods. A seventy-two hours SD mouse model with or without melatonin intervention and fecal microbiota transplantation (FMT) to explore the vital position of Aeromonas-goblet cell interactions in melatonin improving SD-induced colitis. Moreover, Aeromonas or LPS-supplied mice were assessed, and the influence of melatonin on Aeromonas-goblet cell interactions-mediated oxidative stress caused colitis. Furthermore, in vitro experiment investigated the regulation mechanism of melatonin.Results. Our study showed that SD induced colitis, with upregulation of Aeromonas and LPS levels and reductions in goblet cells number and MUC2 protein. Similarly, FMT from SD mice, Aeromonas veronii colonization, and LPS treatment restored the SD-like goblet cells number and MUC2 protein decrease and colitis. Moreover, LPS treatment downregulated the colonic antioxidant capacity. Yet, melatonin intervention reversed all consequence in SD, A.veronii colonization, and LPS-treated mice. In vitro, melatonin reversed A. veronii- or LPS-induced MUC2 depletion in mucus-secreting human HT-29 cells via increasing the expression level of Villin, Tff3, p-GSK-3β, β-catenin, and melatonin receptor 2 (MT2) and decreasing the level of p-IκB, p-P65, ROS, TLR4, and MyD88 proteins, while the improvement effect was blocked with pretreatment with a MT2 antagonist but were mimicked by TLR4 and GSK-3β antagonists and ROS scavengers. Conclusions. Our results demonstrated that melatonin-mediated MT2 inhibits Aeromonas-goblet cell interactions to restore the level of MUC2 production via LPS/TLR4/MyD88/GSK-3β/ROS/NF-κB loop, further improving colitis in SD mice.
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Chen YM, Li Y, Wang X, Wang ZL, Hou JJ, Su S, Zhong WL, Xu X, Zhang J, Wang BM, Wang YM. Effect of Bacillus subtilis, Enterococcus faecium, and Enterococcus faecalis supernatants on serotonin transporter expression in cells and tissues. World J Gastroenterol 2022; 28:532-546. [PMID: 35316963 PMCID: PMC8905020 DOI: 10.3748/wjg.v28.i5.532] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/16/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bacillus subtilis (B. subtilis), Enterococcus faecium (E. faecium), and Enterococcus faecalis (E. faecalis) are probiotics that are widely used in the clinical treatment of irritable bowel syndrome (IBS). Whether the supernatants of these three probiotics can improve gastrointestinal sensation and movement by regulating the serotonin transporter (SERT) expression needs to be clarified.
AIM To investigate whether B. subtilis, E. faecium, and E. faecalis supernatants can upregulate SERT expression in vitro and in vivo.
METHODS Caco-2 and HT-29 cells were stimulated with probiotic culture supernatants for 12 and 24 h, respectively. A male Sprague-Dawley rat model of post-infectious irritable bowel syndrome (PI-IBS) was established and the rats were treated with phosphate-buffered saline (group A) and three probiotics culture supernatants (groups B, C, and D) for 4 wk. The levels of SERT were detected by quantitative PCR and western blotting.
RESULTS The levels of SERT at post-treatment 12 and 24 h were significantly elevated in Caco-2 cells treated with B. subtilis supernatant compared with those in the control group (aP < 0.05). Those levels were markedly upregulated in Caco-2 cells stimulated with E. faecium and E. faecalis supernatants at 24 h (aP < 0.05). In addition, SERT expression in groups B, C, and D was significantly higher than that in group A in the 2nd wk (aP < 0.05). Increased SERT expression was only found in group D in the 3rd wk (aP < 0.05). However, there was no significant difference in SERT expression between the groups in the last week (P > 0.05).
CONCLUSION The supernatants of B. subtilis, E. faecium, and E. faecalis can upregulate SERT expression in intestinal epithelial cells and the intestinal tissues in the rat model of PI-IBS.
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Affiliation(s)
- Yi-Ming Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Ying Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xin Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Ze-Lan Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Jun-Jie Hou
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Shuai Su
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Wei-Long Zhong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xin Xu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Jie Zhang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Bang-Mao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Yu-Ming Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
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Pancreatic Cancer and Gut Microbiome-Related Aspects: A Comprehensive Review and Dietary Recommendations. Nutrients 2021; 13:nu13124425. [PMID: 34959977 PMCID: PMC8709322 DOI: 10.3390/nu13124425] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/04/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota plays a significant role in the human body providing many beneficial effects on the host. However, its dysbiotic alterations may affect the tumorigenic pathway and then trigger the development of pancreatic cancer. This dysbiosis can also modulate the aggressiveness of the tumor, influencing the microenvironment. Because pancreatic cancer is still one of the most lethal cancers worldwide with surgery as the only method that influences prognosis and has curative potential, there is a need to search for other strategies which will enhance the efficiency of standard therapy and improve patients' quality of life. The administration of prebiotics, probiotics, next-generation probiotics (Faecalibacterium prausnitzii, Akkermansia muciniphila), synbiotics, postbiotics, and fecal microbiota transplantation through multiple mechanisms affects the composition of the gut microbiota and may restore its balance. Despite limited data, some studies indicate that the aforementioned methods may allow to achieve better effect of pancreatic cancer treatment and improve therapeutic strategies for pancreatic cancer patients.
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Javanshir N, Hosseini GNG, Sadeghi M, Esmaeili R, Satarikia F, Ahmadian G, Allahyari N. Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System. Biol Proced Online 2021; 23:23. [PMID: 34847891 PMCID: PMC8903605 DOI: 10.1186/s12575-021-00160-w] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 11/04/2021] [Indexed: 12/11/2022] Open
Abstract
Due to the importance of using cost-effective methods for therapeutic purposes, the function of probiotics as safe microorganisms and the study of their relevant functional mechanisms have recently been in the spotlight. Finding the mechanisms of attachment and stability and their beneficial effects on the immune system can be useful in identifying and increasing the therapeutic effects of probiotics. In this review, the functional mechanisms of probiotics were comprehensively investigated. Relevant articles were searched in scientific sources, documents, and databases, including PubMed, NCBI, Bactibace, OptiBac, and Bagel4. The most important functional mechanisms of probiotics and their effects on strengthening the epithelial barrier, competitive inhibition of pathogenic microorganisms, production of antimicrobials, binding and interaction with the host, and regulatory effects on the immune system were discussed. In this regard, the attachment of probiotics to the epithelium is very important because the prerequisite for their proper functioning is to establish a proper connection to the epithelium. Therefore, more attention should be paid to the binding effect of probiotics, including sortase A, a significant factor involved in the expression of sortase-dependent proteins (SDP), on their surface as mediators of intestinal epithelial cell binding. In general, by investigating the functional mechanisms of probiotics, it was concluded that the mechanism by which probiotics regulate the immune system and adhesion capacity can directly and indirectly have preventive and therapeutic effects on a wide range of diseases. However, further study of these mechanisms requires extensive research on various aspects.
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Affiliation(s)
- Nahid Javanshir
- Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology. (NIGEB), P.O. Box: 14155-6343, Tehran, Iran
| | | | - Mahdieh Sadeghi
- Department of Science, Islamic Azad University - Parand Branch, Parand, Iran
| | | | - Fateme Satarikia
- Department of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Gholamreza Ahmadian
- Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology. (NIGEB), P.O. Box: 14155-6343, Tehran, Iran.
| | - Najaf Allahyari
- Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology. (NIGEB), P.O. Box: 14155-6343, Tehran, Iran.
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Probiotics in Intestinal Mucosal Healing: A New Therapy or an Old Friend? Pharmaceuticals (Basel) 2021; 14:ph14111181. [PMID: 34832962 PMCID: PMC8622522 DOI: 10.3390/ph14111181] [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: 10/18/2021] [Revised: 11/08/2021] [Accepted: 11/18/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD), Crohn’s disease, and ulcerative colitis are characterized by chronic and relapsing inflammation, while their pathogenesis remains mostly unelucidated. Gut commensal microbiota seem to be one of the various implicated factors, as several studies have shown a significant decrease in the microbiome diversity of patients with IBD. Although the question of whether microbiota dysbiosis is a causal factor or the result of chronic inflammation remains unanswered, one fact is clear; active inflammation in IBD results in the disruption of the mucus layer structure, barrier function, and also, colonization sites. Recently, many studies on IBD have been focusing on the interplay between mucosal and luminal microbiota, underlining their possible beneficial effect on mucosal healing. Regarding this notion, it has now been shown that specific probiotic strains, when administrated, lead to significantly decreased inflammation, amelioration of colitis, and improved mucosal healing. Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate quantity. The aim of this review was to present and discuss the current findings on the role of gut microbiota and their metabolites in intestinal wound healing and the effects of probiotics on intestinal mucosal wound closure.
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Roberto M, Carconi C, Cerreti M, Schipilliti FM, Botticelli A, Mazzuca F, Marchetti P. The Challenge of ICIs Resistance in Solid Tumours: Could Microbiota and Its Diversity Be Our Secret Weapon? Front Immunol 2021; 12:704942. [PMID: 34489956 PMCID: PMC8417795 DOI: 10.3389/fimmu.2021.704942] [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: 05/04/2021] [Accepted: 08/03/2021] [Indexed: 12/14/2022] Open
Abstract
The human microbiota and its functional interaction with the human body were recently returned to the spotlight of the scientific community. In light of the extensive implementation of newer and increasingly precise genome sequencing technologies, bioinformatics, and culturomic, we now have an extraordinary ability to study the microorganisms that live within the human body. Most of the recent studies only focused on the interaction between the intestinal microbiota and one other factor. Considering the complexity of gut microbiota and its role in the pathogenesis of numerous cancers, our aim was to investigate how microbiota is affected by intestinal microenvironment and how microenvironment alterations may influence the response to immune checkpoint inhibitors (ICIs). In this context, we show how diet is emerging as a fundamental determinant of microbiota’s community structure and function. Particularly, we describe the role of certain dietary factors, as well as the use of probiotics, prebiotics, postbiotics, and antibiotics in modifying the human microbiota. The modulation of gut microbiota may be a secret weapon to potentiate the efficacy of immunotherapies. In addition, this review sheds new light on the possibility of administering fecal microbiota transplantation to modulate the gut microbiota in cancer treatment. These concepts and how these findings can be translated into the therapeutic response to cancer immunotherapies will be presented.
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Affiliation(s)
- Michela Roberto
- Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, Rome, Italy.,Medical Oncology Unit, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Catia Carconi
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant' Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Micaela Cerreti
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant' Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Francesca Matilde Schipilliti
- Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Andrea Botticelli
- Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, Rome, Italy.,Medical Oncology Unit, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Federica Mazzuca
- Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, Rome, Italy
| | - Paolo Marchetti
- Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, Rome, Italy.,Medical Oncology Unit, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
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Milner E, Stevens B, An M, Lam V, Ainsworth M, Dihle P, Stearns J, Dombrowski A, Rego D, Segars K. Utilizing Probiotics for the Prevention and Treatment of Gastrointestinal Diseases. Front Microbiol 2021; 12:689958. [PMID: 34434175 PMCID: PMC8381467 DOI: 10.3389/fmicb.2021.689958] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 07/05/2021] [Indexed: 12/12/2022] Open
Abstract
Probiotics are heavily advertised to promote a healthy gastrointestinal tract and boost the immune system. This review article summarizes the history and diversity of probiotics, outlines conventional in vitro assays and in vivo models, assesses the pharmacologic effects of probiotic and pharmaceutical co-administration, and the broad impact of clinical probiotic utilization for gastrointestinal disease indications.
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Affiliation(s)
- Erin Milner
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
- Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States
| | - Benjamin Stevens
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Martino An
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Victoria Lam
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Michael Ainsworth
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Preston Dihle
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Jocelyn Stearns
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Andrew Dombrowski
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Daniel Rego
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
| | - Katharine Segars
- Department of Chemistry and Life Science, United States Military Academy, West Point, NY, United States
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Lili Q, Xiaohui L, Haiguang M, Jinbo W. Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells. Front Cell Infect Microbiol 2021; 11:668766. [PMID: 34222040 PMCID: PMC8248542 DOI: 10.3389/fcimb.2021.668766] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 06/01/2021] [Indexed: 11/24/2022] Open
Abstract
C. butyricum is a common gut commensal bacterium, which has many positive functions in human intestine. In this study, we investigated the effects of monosaccharide and its derivatives on the adhesion of C. butyricum to the mucus of HT-29 cells. RNA interference was performed to assess the roles of MUC2 and glycan in the adhesion of C. butyricum to HT-29 cells. The effects of C. butyricum on the glycosylation of mucins were assayed with fluorescence microscope. The expression levels of mucins and glycotransferases were also determined. The results showed that C. butyricum could adhere to the mucins secreted by HT-29 cells. Several kinds of monosaccharides inhibited the adhesion of C. butyricum to HT-29 cells, which suggested that the mucus glycan was the attaching sites of this bacterium. Knockdown of MUC2, FUT2 or GALNT7 significantly decreased the numbers of the bacteria adhering to HT-29 cells. When colonizing on the surface of HT-29 cells, C. butyricum could increase the production of mucins, promote the expression of glycotransferase, and induce the glycosylation of mucins. These results demonstrated that the glycan of mucus played important roles in the adhesion of C. butyricum to HT-29 cells. This study indicates for the first time that C. butyricum possesses the ability to modulate the glycosylation profile of mucus secreted by HT-29 cells. These findings contribute to understanding the mechanism of interaction between colonic epithelial cells and commensal bacteria.
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Affiliation(s)
- Qi Lili
- School of Biological and Chemical Engineering, Ningbo Tech University, Ningbo, China
| | - Lu Xiaohui
- Research Department, Ningbo Biomart Lifetech Co.Ltd, Ningbo, China
| | - Mao Haiguang
- School of Biological and Chemical Engineering, Ningbo Tech University, Ningbo, China
| | - Wang Jinbo
- School of Biological and Chemical Engineering, Ningbo Tech University, Ningbo, China
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Su S, Zhang ZF, Wang X, Wang YM, Wang BM. Mechanism of Lactobacillus rhamnosus in treatment of irritable bowel syndrome. Shijie Huaren Xiaohua Zazhi 2021; 29:366-371. [DOI: 10.11569/wcjd.v29.i7.366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a clinically common functional gastrointestinal disease, which affects the quality of life of patients. Therefore, it is of great significance to explore effective treatment methods for IBS. Probiotics can improve the symptoms of IBS patients and their quality of life. Lactobacillus rhamnosus is one of the most studied probiotics and has attracted much attention. . Lactobacillus rhamnosus has been used to treat IBS, and much progress has been made in recent years. Lactobacillus rhamnosus can improve the symptoms of IBS by regulating the imbalance of the intestinal flora, protecting the intestinal barrier function, exerting anti-inflammatory activity, regulating the intestinal immunity, improving visceral hypersensitivity, and inhibiting bacteria. This review aims to elucidate the possible mechanism of Lactobacillus rhamnosus in the treatment of IBS.
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Affiliation(s)
- Shuai Su
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Zhi-Fang Zhang
- Department of Neurology, Tianjin Xiqing Hospital, Tianjin 300380, China
| | - Xin Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Yu-Ming Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Bang-Mao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
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Antilisterial Potential of Lactic Acid Bacteria in Eliminating Listeria monocytogenes in Host and Ready-to-Eat Food Application. MICROBIOLOGY RESEARCH 2021. [DOI: 10.3390/microbiolres12010017] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Listeriosis is a severe food borne disease with a mortality rate of up to 30% caused by pathogenic Listeria monocytogenes via the production of several virulence factors including listeriolysin O (LLO), transcriptional activator (PrfA), actin (Act), internalin (Int), etc. It is a foodborne disease predominantly causing infections through consumption of contaminated food and is often associated with ready-to-eat food (RTE) and dairy products. Common medication for listeriosis such as antibiotics might cause an eagle effect and antibiotic resistance if it is overused. Therefore, exploration of the use of lactic acid bacteria (LAB) with probiotic characteristics and multiple antimicrobial properties is increasingly getting attention for their capability to treat listeriosis, vaccine development, and hurdle technologies. The antilisterial gene, a gene coding to produce antimicrobial peptide (AMP), one of the inhibitory substances found in LAB, is one of the potential key factors in listeriosis treatment, coupled with the vast array of functions and strategies; this review summarizes the various strategies by LAB against L. monocytogenes and the prospect in development of a ‘generally regarded as safe’ LAB for treatment of listeriosis.
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Coleman OI, Haller D. Microbe-Mucus Interface in the Pathogenesis of Colorectal Cancer. Cancers (Basel) 2021; 13:cancers13040616. [PMID: 33557139 PMCID: PMC7913824 DOI: 10.3390/cancers13040616] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/18/2021] [Accepted: 01/27/2021] [Indexed: 12/24/2022] Open
Abstract
Overlying gastrointestinal epithelial cells is the transparent mucus layer that separates the lumen from the host. The dynamic mucus layer serves to lubricate the mucosal surface, to protect underlying epithelial cells, and as a transport medium between luminal contents and epithelial cells. Furthermore, it provides a habitat for commensal bacteria and signals to the underlying immune system. Mucins are highly glycosylated proteins, and their glycocode is tissue-specific and closely linked to the resident microbiota. Aberrant mucin expression and glycosylation are linked to chronic inflammation and gastrointestinal cancers, including colorectal cancer (CRC). Aberrant mucus production compromises the mucus layer and allows bacteria to come into close contact with the intestinal epithelium, potentially triggering unfavorable host responses and the subsequent development of tumors. Here, we review our current understanding of the interaction between the intestinal microbiota and mucus in healthy and CRC subjects. Deep knowledge of the intricate mechanisms of microbe-mucus interactions may contribute to the development of novel treatment strategies for CRC, in which a dysfunctional mucus layer is observed.
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Affiliation(s)
- Olivia I. Coleman
- Department of Nutrition and Immunology, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany;
- Correspondence: ; Tel.: +49-08161-71-2375
| | - Dirk Haller
- Department of Nutrition and Immunology, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany;
- ZIEL—Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany
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Salimi F, Mohammadipanah F. Nanomaterials Versus The Microbial Compounds With Wound Healing Property. FRONTIERS IN NANOTECHNOLOGY 2021. [DOI: 10.3389/fnano.2020.584489] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Age and diabetes related slow-healing or chronic wounds may result in morbidity and mortality through persistent biofilms infections and prolonged inflammatory phase. Nano-materials [metal/metal oxide NPs (39%), lipid vehicles (21%), polymer NPs (19%), ceramic nanoparticles (NPs) (14%), and carbon nanomaterials (NMs) (7%)] can be introduced as a possible next-generation therapy because of either their intrinsic wound healing activity or via carrying bioactive compounds including, antibiotics, antioxidants, growth factor or stem cell. The nanomaterials have been shown to implicate in all four stages of wound healing including hemostasis (polymer NPs, ceramic NPs, nanoceria-6.1%), inflammation (liposome/vesicles/solid lipid NPs/polymer NPs/ceramic NPs/silver NPs/gold NPs/nanoceria/fullerenes/carbon-based NPs-32.7%), proliferation (vesicles/liposome/solid lipid NPs/gold NPs/silver NPs/iron oxide NPs/ceramic NPs/copper NPs/self-assembling elastin-like NPs/nanoceria/micelle/dendrimers/polymer NPs-57.1%), remodeling (iron oxide NPs/nanoceria-4.1%). Natural compounds from alkaloids, flavonoids, retinoids, volatile oil, terpenes, carotenoids, or polyphenolic compounds with proven antioxidant, anti-inflammatory, immunomodulatory, or antimicrobial characteristics are also well known for their potential to accelerate the wound healing process. In the current paper, we survey the potential and properties of nanomaterials and microbial compounds in improving the process of wound and scar healing. Finally, we review the potential biocompounds for incorporation to nano-material in perspective to designate more effective or multivalent wound healing natural or nano-based drugs.
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Deng Y, McDonald OG, Means AL, Peek RM, Washington MK, Acra SA, Polk DB, Yan F. Exposure to p40 in Early Life Prevents Intestinal Inflammation in Adulthood Through Inducing a Long-Lasting Epigenetic Imprint on TGFβ. Cell Mol Gastroenterol Hepatol 2021; 11:1327-1345. [PMID: 33482393 PMCID: PMC8020481 DOI: 10.1016/j.jcmgh.2021.01.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 01/08/2021] [Accepted: 01/11/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Colonization by gut microbiota in early life confers beneficial effects on immunity throughout the host's lifespan. We sought to elucidate the mechanisms whereby neonatal supplementation with p40, a probiotic functional factor, reprograms intestinal epithelial cells for protection against adult-onset intestinal inflammation. METHODS p40 was used to treat young adult mouse colonic (YAMC) epithelial cells with and without deletion of a methyltransferase, su(var)3-9, enhancer-of-zeste and trithorax domain-containing 1β (Setd1β), and mice in early life or in adulthood. Anti-transforming growth factor β (TGFβ)-neutralizing antibodies were administered to adult mice with and without colitis induced by 2,4,6-trinitrobenzenesulfonic acid or dextran sulfate sodium. We examined Setd1b and Tgfb gene expression, TGFβ production, monomethylation and trimethylation of histone H3 on the lysine 4 residue (H3K4me1/3), H3K4me3 enrichment in Tgfb promoter, differentiation of regulatory T cells (Tregs), and the inflammatory status. RESULTS p40 up-regulated expression of Setd1b in YAMC cells. Accordingly, p40 enhanced H3K4me1/3 in YAMC cells in a Setd1β-dependent manner. p40-regulated Setd1β mediated programming the TGFβ locus into a transcriptionally permissive chromatin state and promoting TGFβ production in YAMC. Furthermore, transient exposure to p40 during the neonatal period and in adulthood resulted in the immediate increase in Tgfb gene expression. However, only neonatal p40 supplementation induced the sustained H3K4me1/3 and Tgfb gene expression that persisted into adulthood. Interfering with TGFβ function by neutralizing antibodies diminished the long-lasting effects of neonatal p40 supplementation on differentiation of Tregs and protection against colitis in adult mice. CONCLUSIONS Exposure to p40 in early life enables an epigenetic imprint on TGFβ, leading to long-lasting production of TGFβ by intestinal epithelial cells to expand Tregs and protect the gut against inflammation.
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Affiliation(s)
- Yilin Deng
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Oliver G McDonald
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Anna L Means
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Richard M Peek
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - M Kay Washington
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Sari A Acra
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - D Brent Polk
- Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, California; Department of Biochemistry and Molecular Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California; Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Los Angeles, California
| | - Fang Yan
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
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Li Y, Zhang T, Guo C, Geng M, Gai S, Qi W, Li Z, Song Y, Luo X, Zhang T, Wang N. Bacillus subtilis RZ001 improves intestinal integrity and alleviates colitis by inhibiting the Notch signalling pathway and activating ATOH-1. Pathog Dis 2020; 78:5804729. [PMID: 32166323 DOI: 10.1093/femspd/ftaa016] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 03/11/2020] [Indexed: 02/07/2023] Open
Abstract
Intestinal mucosal barriers help the body resist many intestinal inflammatory diseases, such as inflammatory bowel disease (IBD). In this study, we identified a novel bacterium promoting the repair of intestinal mucosa and investigated the potential mechanisms underlying its activity. Culture supernatant of Bacillus subtilis RZ001 upregulated the expression of mucin 2 (MUC2) and tight junction (TJ) proteins in HT-29 cells in vitro. Oral administration of B. subtilis RZ001 may have significantly reduced symptoms such as the dextran sulfate sodium (DSS)-induced decrease in body weight, shortening of colon length and overproduction of proinflammatory factors. The number of goblet cells and levels of MUC2 and TJ proteins were significantly increased in adult mice fed with B. subtilis RZ001. B. subtilis RZ001 cells upregulated the levels of MUC2 in the intestinal organoids. Furthermore, culture supernatant of B. subtilis RZ001 could suppress the Notch signalling pathway and activate the expression of atonal homolog 1 (Atoh1). The transcription factor Atoh1 is required for intestinal secretory cell differentiation and activates transcription of MUC2 via binding to E-boxes on the MUC2 promoter. Taken together, B. subtilis strain RZ001 has the potential for treating IBD. The present study is helpful to elucidate the mechanisms of B. subtilis action.
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Affiliation(s)
- Yanru Li
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
| | - Tengxun Zhang
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
| | - Congcong Guo
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
| | - Meng Geng
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
| | - Sailun Gai
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
| | - Wei Qi
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
| | - Zhongyuan Li
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
| | - Yajian Song
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
| | - Xuegang Luo
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
| | - Tongcun Zhang
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
| | - Nan Wang
- Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China
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Yan F, Polk DB. Probiotics and Probiotic-Derived Functional Factors-Mechanistic Insights Into Applications for Intestinal Homeostasis. Front Immunol 2020; 11:1428. [PMID: 32719681 PMCID: PMC7348054 DOI: 10.3389/fimmu.2020.01428] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 06/03/2020] [Indexed: 12/20/2022] Open
Abstract
Advances in our understanding of the contribution of the gut microbiota to human health and the correlation of dysbiosis with diseases, including chronic intestinal conditions such as inflammatory bowel disease (IBD), have driven mechanistic investigations of probiotics in intestinal homeostasis and potential clinical applications. Probiotics have been shown to promote intestinal health by maintaining and restoring epithelial function, ensuring mucosal immune homeostasis, and inhibiting pathogenic bacteria. Recent findings reveal an approach for defining previously unrecognized probiotic-derived soluble factors as potential mechanisms of probiotic action. This review focuses on the impact of probiotics and probiotic-derived functional factors, including probiotic products and metabolites by probiotics, on the cellular responses and signaling pathways involved in maintaining intestinal homeostasis. Although there is limited information regarding the translation of probiotic treatment outcomes from in vitro and animal studies to clinical applications, potential approaches for increasing the clinical efficacy of probiotics for IBD, such as those based on probiotic-derived factors, are highlighted in this review. In this era of precision medicine and targeted therapies, more basic, preclinical, and clinical evidence is needed to clarify the efficacy of probiotics in maintaining intestinal health and preventing and treating disease.
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Affiliation(s)
- Fang Yan
- Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - D Brent Polk
- Department of Pediatrics, Keck School of Medicine of University of Southern California, Los Angeles, CA, United States.,Department of Biochemistry and Molecular Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA, United States.,Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital Los Angeles, Los Angeles, CA, United States
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Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer. Oncogene 2020; 39:4925-4943. [PMID: 32514151 PMCID: PMC7314664 DOI: 10.1038/s41388-020-1341-1] [Citation(s) in RCA: 364] [Impact Index Per Article: 72.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 05/17/2020] [Accepted: 05/27/2020] [Indexed: 02/08/2023]
Abstract
Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.
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Rad AH, Aghebati-Maleki L, Kafil HS, Abbasi A. Molecular mechanisms of postbiotics in colorectal cancer prevention and treatment. Crit Rev Food Sci Nutr 2020; 61:1787-1803. [PMID: 32410512 DOI: 10.1080/10408398.2020.1765310] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The occurrence of colorectal cancer (CRC) has been rising expeditiously and anticipated that 2.4 million new occasions of CRC will be detected yearly around the world until the year 2035. Due to some side-effects and complications of conventional CRC therapies, bioactive components such as microbial-derived biomolecules (postbiotics) have been attaining great significance by researchers for adjuvant therapy in CRC patients. The term 'postbiotics' encompasses an extensive range of complex micro- and macro-molecules (<50, 50-100, and 100< kDa) such as inactivated microbial cells, cell fractions or metabolites, which confer various physiological health benefits to the host when administered in adequate amounts. Postbiotics modulate the composition of the gut microbiota and the functionality of the immune system, as well as promote the CRC treatment effectiveness and reduces its side-effects in CRC patients due to possessing anti-oxidant, anti-proliferative, anti-inflammatory, and anti-cancer activities. Presently scientific literature confirms that postbiotics with their unique characteristics in terms of clinical (safe origin), technological (stability), and economic (low production costs) aspects can be used as promising tools for both prevent and adjuvant treat strategies in CRC patients without any serious undesirable side-effects. This review provides an overview of the concept and safety issues regarding postbiotics, with emphasis on their biological role in the prevention and treatment of CRC.
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Affiliation(s)
- Aziz Homayouni Rad
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Hossein Samadi Kafil
- Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amin Abbasi
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Student's research committee, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Dudík B, Kiňová Sepová H, Bilka F, Pašková Ľ, Bilková A. Mucin pre-cultivated Lactobacillus reuteri E shows enhanced adhesion and increases mucin expression in HT-29 cells. Antonie van Leeuwenhoek 2020; 113:1191-1200. [DOI: 10.1007/s10482-020-01426-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 05/06/2020] [Indexed: 12/23/2022]
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Parisa A, Roya G, Mahdi R, Shabnam R, Maryam E, Malihe T. Anti-cancer effects of Bifidobacterium species in colon cancer cells and a mouse model of carcinogenesis. PLoS One 2020; 15:e0232930. [PMID: 32401801 PMCID: PMC7219778 DOI: 10.1371/journal.pone.0232930] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 04/25/2020] [Indexed: 01/20/2023] Open
Abstract
INTRODUCTION Probiotics are suggested to prevent colorectal cancer (CRC). This study aimed to investigate the anticancer properties of some potential probiotics in vitro and in vivo. MATERIALS AND METHODS Anticancer effects of the following potential probiotic groups were investigated in LS174T cancer cells compared to IEC-18 normal cells. 1. a single strain of Bifidobacterium. breve, 2. a single strain of Lactobacillus. reuteri, 3. a cocktail of 5 strains of Lactobacilli (LC), 4. a cocktail of 5 strains of Bifidobacteria (BC), 5. a cocktail of 10 strains from Lactobacillus and Bifidobacterium (L+B). Apoptosis rate, EGFR, HER-2 and PTGS-2 (COX-2 protein) expression levels were assessed as metrics of evaluating anticancer properties. Effect of BC, as the most effective group in vitro, was further assessed in mice models. RESULTS BC induced ~21% and only ~3% apoptosis among LS174T and IEC-18 cells respectively. BC decreased the expression of EGFR by 4.4 folds, HER-2 by 6.7 folds, and PTGS-2 by 20 folds among the LS174T cells. In all these cases, BC did not interfere significantly with the expression of the genes in IEC-18 cells. This cocktail has caused only 1.1 folds decrease, 1.8 folds increase and 1.7 folds decrease in EGFR, HER-2 and PTGS-2 expression, respectively. Western blot analysis confirmed these results in the protein level. BC significantly ameliorated the disease activity index, restored colon length, inhibited the increase in incidence and progress of tumors to higher stages and grades. CONCLUSIONS BC was the most efficient treatment in this study. It had considerable "protective" anti-cancer properties and concomitantly down regulated EGFR, HER-2 and PTGS-2 (COX-2), while having significant anti-CRC effects on CRC mice models. In general, this potential probiotic could be considered as a suitable nutritional supplement to treat and prevent CRC.
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Affiliation(s)
- Asadollahi Parisa
- Microbial Biotechnology Research Centre, Iran University of Medical Sciences, Tehran, Iran
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ghanavati Roya
- Microbial Biotechnology Research Centre, Iran University of Medical Sciences, Tehran, Iran
- Behbahan Faculty of Medical Science, Behbahan, Iran
| | - Rohani Mahdi
- Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran
| | - Razavi Shabnam
- Microbial Biotechnology Research Centre, Iran University of Medical Sciences, Tehran, Iran
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Esghaei Maryam
- Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Talebi Malihe
- Microbial Biotechnology Research Centre, Iran University of Medical Sciences, Tehran, Iran
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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