1
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Neurath MF, Artis D, Becker C. The intestinal barrier: a pivotal role in health, inflammation, and cancer. Lancet Gastroenterol Hepatol 2025; 10:573-592. [PMID: 40086468 DOI: 10.1016/s2468-1253(24)00390-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 11/08/2024] [Accepted: 11/15/2024] [Indexed: 03/16/2025]
Abstract
The intestinal barrier serves as a boundary between the mucosal immune system in the lamina propria and the external environment of the intestinal lumen, which contains a diverse array of microorganisms and ingested environmental factors, including pathogens, food antigens, toxins, and other foreign substances. This barrier has a central role in regulating the controlled interaction between luminal factors and the intestinal immune system. Disruptions of intestinal epithelial cells, which serve as a physical barrier, or the antimicrobial peptides and mucins they produce, which act as a chemical barrier, can lead to a leaky gut. In this state, the intestinal wall is unable to efficiently separate the intestinal flora and luminal contents from the intestinal immune system. The subsequent activation of the immune system has an important role in the pathogenesis of inflammatory bowel disease, as well as in metabolic dysfunction-associated steatohepatitis, primary sclerosing cholangitis, and colorectal cancer. Dysregulated intestinal barrier integrity has also been described in patients with chronic inflammatory diseases outside the gastrointestinal tract, including rheumatoid arthritis and neurodegenerative disorders. Mechanistic studies of barrier dysfunction have revealed that the subsequent local activation and systemic circulation of activated immune cells and the cytokines they secrete, as well as extracellular vesicles, promote proinflammatory processes within and outside the gastrointestinal tract. In this Review, we summarise these findings and highlight several new therapeutic concepts currently being developed that attempt to control inflammatory processes via direct or indirect modulation of intestinal barrier function.
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Affiliation(s)
- Markus F Neurath
- Medical Clinic 1, Department of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
| | - David Artis
- Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY, USA; Joan and Sanford I Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA; Allen Discovery Center for Neuroimmune Interactions, Weill Cornell Medicine, Cornell University, New York, NY, USA
| | - Christoph Becker
- Medical Clinic 1, Department of Gastroenterology, Ludwig Demling Endoscopy Center of Excellence, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
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2
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Chi J, Patterson JS, Jin Y, Kim KJ, Lalime N, Hawley D, Lewis F, Li L, Wang X, Campen MJ, Cui JY, Gu H. Metabolic Reprogramming in Gut Microbiota Exposed to Polystyrene Microplastics. Biomedicines 2025; 13:446. [PMID: 40002859 PMCID: PMC11853289 DOI: 10.3390/biomedicines13020446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 01/26/2025] [Accepted: 02/08/2025] [Indexed: 02/27/2025] Open
Abstract
Background: Microplastics (MPs) are small plastic fragments with diameters less than 5 mm in size and are prevalent in everyday essentials and consumables. Large global plastic production has now led to a flooding of MPs in our natural environment. Due to their detrimental impacts on the planet's ecosystems and potentially our health, MPs have emerged as a significant public health concern. In this pilot study, we hypothesize that MPs exposure will negatively affect gut microbiota composition and function, in which metabolic reprogramming plays an important role. Methods: Using in vitro experiments, three bacterial strains (Escherichia coli MG1655, Nissle 1917, and Lactobacillus rhamnosus) were selected to investigate the impacts of MPs exposure. The bacterial strains were individually cultured in an anaerobic chamber and exposed to 1 µm polystyrene MPs at various concentrations (0, 10, 20, 50, 100, and 500 µg/mL) in the culture medium. Results: MPs exposure reduced the growth of all three bacterial strains in a dose-dependent manner. Liquid chromatography mass spectrometry (LC-MS)-based untargeted metabolomics revealed significant differences in multiple metabolic pathways, such as sulfur metabolism and amino sugar and nucleotide sugar metabolism. In addition, we extracted gut microbiota from C57BL/6 mice, and 16S rRNA sequencing results showed a significant upregulation of Lactobacillales and a significant reduction in Erysipelotrichales due to MPs exposure. Furthermore, targeted and untargeted metabolomics corroborated the in vitro results and revealed alterations in microbial tryptophan metabolism and energy producing pathways, such as glycolysis/gluconeogenesis and the pentose phosphate pathway. Conclusions: These findings provide evidence that MPs exposure causes comprehensive changes to healthy gut microbiota, which may also provide insights into the mechanistic effects of MPs exposure in humans.
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Affiliation(s)
- Jinhua Chi
- College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; (J.C.); (J.S.P.); (L.L.)
- Center for Translational Science, Florida International University, Port St. Lucie, FL 34987, USA;
| | - Jeffrey S. Patterson
- College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; (J.C.); (J.S.P.); (L.L.)
| | - Yan Jin
- Center for Translational Science, Florida International University, Port St. Lucie, FL 34987, USA;
| | - Kyle Joohyung Kim
- Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA; (K.J.K.); (J.Y.C.)
| | - Nicole Lalime
- School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287, USA;
| | - Daniella Hawley
- School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA; (D.H.); (X.W.)
| | - Freeman Lewis
- Environmental Health Sciences, Florida International University, Miami, FL 33199, USA;
| | - Lingjun Li
- College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; (J.C.); (J.S.P.); (L.L.)
| | - Xuan Wang
- School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA; (D.H.); (X.W.)
| | - Matthew J. Campen
- Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences, Albuquerque, NM 87106, USA;
| | - Julia Yue Cui
- Department of Environmental & Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA; (K.J.K.); (J.Y.C.)
| | - Haiwei Gu
- College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; (J.C.); (J.S.P.); (L.L.)
- Center for Translational Science, Florida International University, Port St. Lucie, FL 34987, USA;
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3
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Zhang Q, Yang Y, Chen Y, Ban S, Gu S, Li F, Xue M, Sun J, Li X, Tie S. Optimization of pH-responsive microgel for the co-delivery of Weizmannia coagulans and procyanidins to enhance survival rate and tolerance. Food Chem 2025; 464:141691. [PMID: 39442217 DOI: 10.1016/j.foodchem.2024.141691] [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: 05/23/2024] [Revised: 09/29/2024] [Accepted: 10/15/2024] [Indexed: 10/25/2024]
Abstract
The purpose of this study was to prepare a pH-responsive microgel for co-delivering Weizmannia coagulans 99 (BC99) and procyanidins (PCs) to enhance the survival rate and tolerance of probiotics in complex micro-environment. The effects of different concentrations of PCs on the properties of microgels were optimized, and found that the spherical microgels had higher encapsulation efficiency (90.27 ± 2.51%) and smaller size when the concentration of PCs was 20 μg/mL. The interaction among PCs, pectin and protein could effectively improve the survival rate of BC99 under different pH, bile salt, digestive enzyme and temperature conditions, maintain their stability in acidic gastric fluid, and realize the release of probiotics in neutral intestinal fluid. Moreover, the microgel was able to protect BC99 against H2O2 and antibiotics. This work provides a pH-responsive co-loaded microgels for BC99 and PCs, and has the potential in the loading and delivery of other probiotics and polyphenols.
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Affiliation(s)
- Qing Zhang
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Yujin Yang
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Yannan Chen
- College of Food Science and Engineering, Shandong Agricultural University, Tai'an 270018, China; College of Food Science and Engineering, Shandong Agricultural University, Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, Tai'an 271018, China
| | - Shuoshuo Ban
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Shaobin Gu
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China.
| | - Fang Li
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Mengmeng Xue
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Jianrui Sun
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China
| | - Xin Li
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China.
| | - Shanshan Tie
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China.
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4
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Chen A, Gong Y, Wu S, Du Y, Liu Z, Jiang Y, Li J, Miao YB. Navigating a challenging path: precision disease treatment with tailored oral nano-armor-probiotics. J Nanobiotechnology 2025; 23:72. [PMID: 39893419 PMCID: PMC11786591 DOI: 10.1186/s12951-025-03141-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/19/2025] [Indexed: 02/04/2025] Open
Abstract
Oral probiotics have significant potential for preventing and treating many diseases. Yet, their efficacy is often hindered by challenges related to survival and colonization within the gastrointestinal tract. Nanoparticles emerge as a transformative solution, offering robust protection and enhancing the stability and bioavailability of these probiotics. This review explores the innovative application of nanoparticle-armored engineered probiotics for precise disease treatment, specifically addressing the physiological barriers associated with oral administration. A comprehensive evaluation of various nano-armor probiotics and encapsulation methods is provided, carefully analyzing their respective merits and limitations, alongside strategies to enhance probiotic survival and achieve targeted delivery and colonization within the gastrointestinal tract. Furthermore, the review explores the potential clinical applications of nano-armored probiotics in precision therapeutics, critically addressing safety and regulatory considerations, and proposing the innovative concept of 'probiotic intestinal colonization with nano armor' for brain-targeted therapies. Ultimately, this review aspires to guide the advancement of nano-armored probiotic therapies, driving progress in precision medicine and paving the way for groundbreaking treatment modalities.
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Affiliation(s)
- Anmei Chen
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China
- Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu, 610000, China
| | - Ying Gong
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China
- Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu, 610000, China
| | - Shaoquan Wu
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China
- Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu, 610000, China
| | - Ye Du
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China
- Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu, 610000, China
| | - Zhijun Liu
- Urology Institute of Shenzhen University, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen, 518000, China
| | - Yuhong Jiang
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China.
| | - Jiahong Li
- School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610041, China.
| | - Yang-Bao Miao
- Department of Haematology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine of University of Electronic Science and Technology of China, No. 32, West Section 2, First Ring Road, Qingyang District, Chengdu, 610000, China.
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5
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Chen W, Chen R, Sun Y, Wang H, Chen Z, Chen L, Huang G, Lin G, Hong D. Facile Labeling of Gram-Negative Bacteria with NIR-II Fluorescent Nanoprobes for Intestinal Bacteria Imaging. ACS OMEGA 2025; 10:2044-2050. [PMID: 39866610 PMCID: PMC11755162 DOI: 10.1021/acsomega.4c08239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 12/19/2024] [Accepted: 12/30/2024] [Indexed: 01/28/2025]
Abstract
The gut bacteria not only play a crucial role in maintaining human health but also exhibit close associations with the occurrence of numerous diseases. Understanding the physiological and pathological functions of gut bacteria and enabling early diagnosis of gut diseases heavily relies on accurate knowledge about their in vivo distribution. Consequently, there is a significant demand for noninvasive imaging techniques capable of providing real-time localization information regarding gut bacteria. In this work, we developed a second near-infrared (NIR-II) fluorescent nanoprobe labeling-based visualization strategy for real-time tracking of the biodistribution of Gram-negative bacteria in the gastrointestinal tract of mice. By utilizing positively charged silver sulfide quantum dots (Ag2S QDs) as NIR-II nanoprobes and exploiting electrostatic interactions to efficiently label the Gram-negative probiotic Escherichia coli Nissle 1917 with negative surface charges, we have achieved rapid and effective labeling. Leveraging the exceptional NIR-II fluorescent performance of Ag2S QDs, our approach enables high spatiotemporal resolution visualization via NIR-II imaging in mouse gastrointestinal areas where Ag2S QD-labeled probiotics are present, facilitating real-time in vivo tracking capabilities for these labeled probiotics. This work not only establishes a powerful intestinal bacterial imaging strategy but also introduces novel concepts for constructing nanomaterial-bacteria hybrid systems.
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Affiliation(s)
- Wenwen Chen
- College
of Biological Science and Engineering, Fuzhou
University, Fuzhou 350108, P. R. China
| | - Rong Chen
- College
of Biological Science and Engineering, Fuzhou
University, Fuzhou 350108, P. R. China
| | - Yutong Sun
- College
of Biological Science and Engineering, Fuzhou
University, Fuzhou 350108, P. R. China
| | - Han Wang
- College
of Biological Science and Engineering, Fuzhou
University, Fuzhou 350108, P. R. China
| | - Zhenyu Chen
- College
of Biological Science and Engineering, Fuzhou
University, Fuzhou 350108, P. R. China
| | - Liqun Chen
- College
of Biological Science and Engineering, Fuzhou
University, Fuzhou 350108, P. R. China
| | - Guoming Huang
- College
of Biological Science and Engineering, Fuzhou
University, Fuzhou 350108, P. R. China
| | - Guifang Lin
- Department
of Radiology, Fujian Medical University
Union Hospital, Fuzhou 350001, P. R. China
| | - Dengke Hong
- Department
of Vascular Surgery, Fujian Medical University
Union Hospital, Fuzhou 350001, P. R. China
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6
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Qiao T, Wen XH. Exploring gut microbiota as a novel therapeutic target in Crohn's disease: Insights and emerging strategies. World J Gastroenterol 2025; 31:100827. [PMID: 39811502 PMCID: PMC11684203 DOI: 10.3748/wjg.v31.i2.100827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 09/30/2024] [Accepted: 11/15/2024] [Indexed: 12/18/2024] Open
Abstract
Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.
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Affiliation(s)
- Tong Qiao
- Department of Clinical Medicine, Jinan University, Guangzhou 510632, Guangdong Province, China
| | - Xian-Hui Wen
- College of Life Science and Technology, Jinan University, Guangzhou 510632, Guangdong Province, China
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7
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Wang Y, Liu Y, Su X, Niu L, Li N, Xu C, Sun Z, Guo H, Shen S, Yu M. Non-pathogenic Trojan horse Nissle1917 triggers mitophagy through PINK1/Parkin pathway to discourage colon cancer. Mater Today Bio 2024; 29:101273. [PMID: 39415764 PMCID: PMC11480251 DOI: 10.1016/j.mtbio.2024.101273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 09/21/2024] [Accepted: 09/25/2024] [Indexed: 10/19/2024] Open
Abstract
Bacteria-mediated antitumor therapy has gained widespread attention for its innate tumor-targeting capability and excellent immune activation properties. Nevertheless, the clinical approval of bacterial therapies remains elusive primarily due to the formidable challenge of balancing safety with enhancing in vivo efficacy. In this study, leveraging the probiotic Escherichia coli Nissle1917 (EcN) emerges as a promising approach for colon cancer therapy, offering a high level of safety attributed to its lack of virulence factors and its tumor-targeting potential owing to its obligate anaerobic nature. Specifically, we delineate the erythrocyte (RBC) membrane-camouflaged EcN, termed as Trojan horse EcN@RBC, which triggers apoptosis in tumor cells by mitigating mitochondrial membrane potential (MMP) and subsequently activating the PINK1/Parkin pathway associated with mitophagy. Concurrently, the decline in MMP induced by mitophagy disrupts the mitochondrial permeability transition pore (MPTP), leading to the release of Cytochrome C and subsequent apoptosis induction. Moreover, synergistic effects were observed through the combination of the autophagy activator rapamycin, bolstering the antitumor efficacy in vivo. These findings offer novel insights into probiotic-mediated antitumor mechanisms and underscore the therapeutic potential of EcN@RBC for colon cancer patients.
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Affiliation(s)
- Yang Wang
- Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
- Central Laboratory, First Affiliated Hospital, Institute (college) of Integrative Medicine, Dalian Medical University, Dalian, 116011, China
| | - Yao Liu
- Clinical Oncology Center, Shanghai Municipal Hospital of TCM, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China
| | - Xiaomin Su
- Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
- Central Laboratory, First Affiliated Hospital, Institute (college) of Integrative Medicine, Dalian Medical University, Dalian, 116011, China
| | - Lili Niu
- Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
- Central Laboratory, First Affiliated Hospital, Institute (college) of Integrative Medicine, Dalian Medical University, Dalian, 116011, China
| | - Nannan Li
- Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
- Central Laboratory, First Affiliated Hospital, Institute (college) of Integrative Medicine, Dalian Medical University, Dalian, 116011, China
| | - Ce Xu
- Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
- Central Laboratory, First Affiliated Hospital, Institute (college) of Integrative Medicine, Dalian Medical University, Dalian, 116011, China
| | - Zanya Sun
- Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
- Central Laboratory, First Affiliated Hospital, Institute (college) of Integrative Medicine, Dalian Medical University, Dalian, 116011, China
| | - Huishu Guo
- Central Laboratory, First Affiliated Hospital, Institute (college) of Integrative Medicine, Dalian Medical University, Dalian, 116011, China
| | - Shun Shen
- Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China
| | - Minghua Yu
- Fudan University Clinical Research Center for Cell-based Immunotherapy & Department of Oncology, Fudan University Pudong Medical Center, Shanghai, 201399, China
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8
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Huang Y, Peng S, Zeng R, Yao H, Feng G, Fang J. From probiotic chassis to modification strategies, control and improvement of genetically engineered probiotics for inflammatory bowel disease. Microbiol Res 2024; 289:127928. [PMID: 39405668 DOI: 10.1016/j.micres.2024.127928] [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: 03/28/2024] [Revised: 10/05/2024] [Accepted: 10/05/2024] [Indexed: 11/02/2024]
Abstract
With the rising morbidity of inflammatory bowel disease (IBD) year by year, conventional therapeutic drugs with systemic side effects are no longer able to meet the requirements of patients. Probiotics can improve gut microbiota, enhance intestinal barrier function, and regulate mucosal immunity, making them a potential complementary or alternative therapy for IBD. To compensate for the low potency of probiotics, genetic engineering technology has been widely used to improve their therapeutic function. In this review, we systematically summarize the genetically engineered probiotics used for IBD treatment, including probiotic chassis, genetic modification strategies, methods for controlling probiotics, and means of improving efficacy. Finally, we provide prospects on how genetically engineered probiotics can be extended to clinical applications.
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Affiliation(s)
- Yuewen Huang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China
| | - Shan Peng
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China
| | - Rong Zeng
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China
| | - Hao Yao
- Changsha IMADEK Intelligent Technology Co., LTD, Changsha 410081, China
| | - Guangfu Feng
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China.
| | - Jun Fang
- College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China.
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9
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Kaymak Ertekin F, Köprüalan Aydın Ö, Altay Ö. Enhancing Viability of Lactobacillus plantarumBG24 Through Optimized Spray Drying: Insights Into Process Parameters, Carrier Agents, Comparative Analysis With Freeze Drying, and Storage Condition Influences. Food Sci Nutr 2024; 12:10330-10346. [PMID: 39723077 PMCID: PMC11666833 DOI: 10.1002/fsn3.4572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 08/09/2024] [Accepted: 10/13/2024] [Indexed: 12/28/2024] Open
Abstract
This study investigated the survival dynamics of Lactobacillus plantarum BG24, a probiotic strain, within reconstituted skim milk (RSM) and yeast extract (YE) matrices during the spray-drying (SD) process, encompassing of inlet/outlet air temperatures. Notably, optimum SD parameters were found to be an inlet air temperature of 150°C and outlet air temperature of 83°C, that achieving high viability (92.23%), and reducing both moisture content (MC) (3.57%) and water activity (a w) (0.266). The use of soy protein isolate (SPI), gum Arabic (GA), RSM, maltodextrin (MD), sucrose (SUC), and lactose in binary mixtures or alone was investigated in terms of the best survival rate of probiotic bacteria, and RSM alone and RSM + GA and SPI alone were found to be the best drying carriers giving higher viability during SD. SD at optimum process temperatures and freeze drying (FD) were compared in the survival rate of probiotic bacteria in the carrier of RSM with YE, and FD samples showed a higher survival rate (97.69%) than SD samples. It was determined that the storage temperature (4°C and 20°C) had an impact on the glass transition temperature, MC, a w, and cell viability. Increased storage temperature led to a greater decrease in cell viability, especially for SD probiotic powders. These findings furnish critical insights into the intricate interplay among process parameters, carrier agents, drying techniques, and storage conditions, thereby elucidating avenues for refining probiotic preservation strategies within the ambit of SD, and by extension, in the domains of food and pharmaceutical sciences.
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Affiliation(s)
| | | | - Özgül Altay
- Department of Food Engineering, Faculty of EngineeringEge UniversityİzmirTurkey
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10
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de Assis Glória R, da Silva TF, Gomes TAM, Vital KD, Fernandes SOA, Cardoso VN, Ferreira Ê, Chatel JM, Langella P, Cherbuy C, Le Loir Y, Jan G, Guédon É, Azevedo VADC. Postbiotic Effect of Escherichia coli CEC15 and Escherichia coli Nissle 1917 on a Murine Model of 5-FU-induced Intestinal Mucositis. Probiotics Antimicrob Proteins 2024:10.1007/s12602-024-10414-0. [PMID: 39589689 DOI: 10.1007/s12602-024-10414-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2024] [Indexed: 11/27/2024]
Abstract
Probiotics are live microorganisms that, when administered in adequate amounts, can bring health benefits to the host. Most of these organisms are found naturally in the human gastrointestinal tract. Escherichia coli strains Nissle 1917 (EcN), and CEC15 have shown beneficial effects in murine models of intestinal inflammation, such as colitis and mucositis. The present study evaluated the effects as postbiotic of heat-inactivated and cell-free supernatant preparations of EcN and CEC15 in attenuating 5-fluorouracil (5-FU)-induced intestinal mucositis in mice and compared them with the probiotic effects of the live preparations. BALB/c mice were fed, by daily gavage, with 1010 CFU of live or inactivated bacteria or with 300 µL of cell-free supernatant for 12 days. On the 10th day, all animals, except for the control group, received an intraperitoneal injection of 5-FU (300 mg/kg). After 72 h of 5-FU administration, animals were euthanized, and the ileum and blood were collected for analysis. Treatments with live and heat-inactivated CEC15 mitigated weight loss, preserved intestinal length, reduced histological damage, maintained goblet cells, decreased neutrophil infiltration, and modulated expression of inflammatory and barrier genes when compared to 5-FU mucositis controls. EcN showed more limited effects. CEC15 upregulated mRNA expression of the mucin MUC2 and tight junction protein TJP1. CEC15 demonstrated protective effects against 5-FU-induced mucositis, whether administered with live, heat-inactivated, or cell-free supernatant. This suggests that CEC15 mediates a protective response via secreted metabolites and does not require viability. The postbiotic forms of CEC15 present advantages for use in immunocompromised patients. This study elucidates the anti-inflammatory and barrier-protective effects of CEC15 against intestinal mucositis.
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Affiliation(s)
- Rafael de Assis Glória
- Institute of Biological Sciences, Department of Genetics, Ecology, and Evolution, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Tales Fernando da Silva
- Institute of Biological Sciences, Department of Genetics, Ecology, and Evolution, Federal University of Minas Gerais, Belo Horizonte, Brazil
- INRAE, Institut Agro, STLO, 35042, Rennes, France
| | - Tomás Andrade Magalhães Gomes
- Institute of Biological Sciences, Department of Genetics, Ecology, and Evolution, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Kátia Duarte Vital
- Department of clinical and toxicological analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Simone Odília Antunes Fernandes
- Department of clinical and toxicological analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Valbert Nascimento Cardoso
- Department of clinical and toxicological analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Ênio Ferreira
- Department of General Pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Jean-Mark Chatel
- Université Paris Saclay, INRAE, AgroParisTech, UMR1319, MICALIS, Paris, France
| | - Philippe Langella
- Université Paris Saclay, INRAE, AgroParisTech, UMR1319, MICALIS, Paris, France
| | - Claire Cherbuy
- Université Paris Saclay, INRAE, AgroParisTech, UMR1319, MICALIS, Paris, France
| | - Yves Le Loir
- INRAE, Institut Agro, STLO, 35042, Rennes, France
| | - Gwénaël Jan
- INRAE, Institut Agro, STLO, 35042, Rennes, France
| | - Éric Guédon
- INRAE, Institut Agro, STLO, 35042, Rennes, France
| | - Vasco Ariston de Carvalho Azevedo
- Institute of Biological Sciences, Department of Genetics, Ecology, and Evolution, Federal University of Minas Gerais, Belo Horizonte, Brazil.
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11
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Jans M, Kolata M, Blancke G, D'Hondt A, Gräf C, Ciers M, Sze M, Thiran A, Petta I, Andries V, Verbandt S, Shokry E, Sumpton D, Vande Voorde J, Berx G, Tejpar S, van Loo G, Iliev ID, Remaut H, Vereecke L. Colibactin-driven colon cancer requires adhesin-mediated epithelial binding. Nature 2024; 635:472-480. [PMID: 39506107 DOI: 10.1038/s41586-024-08135-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 09/30/2024] [Indexed: 11/08/2024]
Abstract
Various bacteria are suggested to contribute to colorectal cancer (CRC) development1-5, including pks+ Escherichia coli, which produces the genotoxin colibactin that induces characteristic mutational signatures in host epithelial cells6. However, it remains unclear how the highly unstable colibactin molecule is able to access host epithelial cells to cause harm. Here, using the microbiota-dependent ZEB2-transgenic mouse model of invasive CRC7, we demonstrate that the oncogenic potential of pks+ E. coli critically depends on bacterial adhesion to host epithelial cells, mediated by the type 1 pilus adhesin FimH and the F9 pilus adhesin FmlH. Blocking bacterial adhesion using a pharmacological FimH inhibitor attenuates colibactin-mediated genotoxicity and CRC exacerbation. We also show that allelic switching of FimH strongly influences the genotoxic potential of pks+ E. coli and can induce a genotoxic gain-of-function in the probiotic strain Nissle 1917. Adhesin-mediated epithelial binding subsequently allows the production of the genotoxin colibactin in close proximity to host epithelial cells, which promotes DNA damage and drives CRC development. These findings present promising therapeutic routes for the development of anti-adhesive therapies aimed at mitigating colibactin-induced DNA damage and inhibiting the initiation and progression of CRC, particularly in individuals at risk for developing CRC.
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Affiliation(s)
- Maude Jans
- VIB Center for Inflammation Research, Ghent, Belgium
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
| | - Magdalena Kolata
- Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium
- Structural & Molecular Microbiology, VIB-VUB Centre for Structural Biology, Brussels, Belgium
| | - Gillian Blancke
- VIB Center for Inflammation Research, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Aline D'Hondt
- Structural & Molecular Microbiology, VIB-VUB Centre for Structural Biology, Brussels, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Claudia Gräf
- Structural & Molecular Microbiology, VIB-VUB Centre for Structural Biology, Brussels, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Maarten Ciers
- VIB Center for Inflammation Research, Ghent, Belgium
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Mozes Sze
- VIB Center for Inflammation Research, Ghent, Belgium
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Alexandra Thiran
- VIB Center for Inflammation Research, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Ioanna Petta
- VIB Center for Inflammation Research, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Vanessa Andries
- VIB Center for Inflammation Research, Ghent, Belgium
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Sara Verbandt
- Department of Oncology, Catholic University Leuven, Leuven, Belgium
| | - Engy Shokry
- Cancer Research UK Scotland Institute, Glasgow, UK
| | - David Sumpton
- Cancer Research UK Scotland Institute, Glasgow, UK
- School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, UK
| | - Johan Vande Voorde
- School of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, UK
| | - Geert Berx
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
| | - Sabine Tejpar
- Department of Oncology, Catholic University Leuven, Leuven, Belgium
| | - Geert van Loo
- VIB Center for Inflammation Research, Ghent, Belgium
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium
| | - Iliyan D Iliev
- Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA
| | - Han Remaut
- Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium
- Structural & Molecular Microbiology, VIB-VUB Centre for Structural Biology, Brussels, Belgium
| | - Lars Vereecke
- VIB Center for Inflammation Research, Ghent, Belgium.
- Cancer Research Institute Ghent (CRIG), Ghent, Belgium.
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
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12
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Gu S, Zhao X, Wan F, Gu D, Xie W, Gao C. Intracellularly Gelated Macrophages Loaded with Probiotics for Therapy of Colitis. NANO LETTERS 2024; 24:13504-13512. [PMID: 39418594 DOI: 10.1021/acs.nanolett.4c02699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2024]
Abstract
Probiotics therapy has garnered significant attention in the treatment of inflammatory bowel disease (IBD). However, a large number of oral administrated probiotics are inactivated after passing through the gastric acid environment, and their ability to colonize in the intestine is also weak. Herein, this study develops a novel probiotics formulation (GM-EcN) by incorporating Escherichia coli Nissle 1917 (EcN) into intracellularly gelated macrophages (GM). Intracellular hydrogel is designed to load and prevent EcN from digestion in gastric juice, and GM acts as a macrophage-like carrier to carry the attached probiotics to colonize in the inflammatory intestine. In addition, hydrogel serves as an ideal cytoskeletal structure to maintain the intact cell morphology and membrane structure of GM, comparable to source macrophages. Due to the receptor-ligand interaction, inflammation-related membrane proteins enable GM as a cell sponge to sequestrate and neutralize multiple inflammatory cytokines. In vivo treatment demonstrates that GM-EcN efficiently alleviates IBD symptoms and enhances gut microbiota recovery.
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Affiliation(s)
- Siyao Gu
- State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
- Open FIESTA Center, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
- Shenzhen Key Laboratory of Health Science and Technology, Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
| | - Xiaona Zhao
- Department of Laboratory Medicine, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China
- Guangxi University of Chinese Medicine, 530004 Nanning, China
| | - Fang Wan
- State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
- Shenzhen Key Laboratory of Health Science and Technology, Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
| | - Dayong Gu
- Department of Laboratory Medicine, Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China
| | - Weidong Xie
- State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
- Open FIESTA Center, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
- Shenzhen Key Laboratory of Health Science and Technology, Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China
| | - Cheng Gao
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, P. R. China
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13
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Jian C, Yinhang W, Jing Z, Zhanbo Q, Zefeng W, Shuwen H. Escherichia coli on colorectal cancer: A two-edged sword. Microb Biotechnol 2024; 17:e70029. [PMID: 39400440 PMCID: PMC11472651 DOI: 10.1111/1751-7915.70029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 09/26/2024] [Indexed: 10/15/2024] Open
Abstract
Escherichia coli (E. coli) is a ubiquitous symbiotic bacterium in the gut, and the diversity of E. coli genes determines the diversity of its functions. In this review, the two-edged sword theory was innovatively proposed. For the question 'how can we harness the ambivalent nature of E. coli to screen and treat CRC?', in terms of CRC screening, the variations in the abundance and subtypes of E. coli across different populations present an opportunity to utilise it as a biomarker, while in terms of CRC treatment, the natural beneficial effect of E. coli on CRC may be limited, and engineered E. coli, particularly certain subtypes with probiotic potential, can indeed play a significant role in CRC treatment. It seems that the favourable role of E. coli as a genetic tool lies not in its direct impact on CRC but its potential as a research platform that can be integrated with various technologies such as nanoparticles, imaging methods, and synthetic biology modification. The relationship between gut microflora and CRC remains unclear due to the complex diversity and interaction of gut microflora. Therefore, the application of E. coli should be based on the 'One Health' view and take the interactions between E. coli and other microorganisms, host, and environmental factors, as well as its own changes into account. In this paper, the two-edged sword role of E. coli in CRC is emphasised to realise the great potential of E. coli in CRC screening and treatment.
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Affiliation(s)
- Chu Jian
- Huzhou Central HospitalAffiliated Central Hospital Huzhou UniversityHuzhouZhejiangPeople's Republic of China
- Huzhou Central HospitalFifth Affiliated Clinical Medical College of Zhejiang Chinese Medical UniversityHuzhouZhejiangPeople's Republic of China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of HuzhouHuzhouZhejiangPeople's Republic of China
| | - Wu Yinhang
- Huzhou Central HospitalAffiliated Central Hospital Huzhou UniversityHuzhouZhejiangPeople's Republic of China
- Huzhou Central HospitalFifth Affiliated Clinical Medical College of Zhejiang Chinese Medical UniversityHuzhouZhejiangPeople's Republic of China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of HuzhouHuzhouZhejiangPeople's Republic of China
| | - Zhuang Jing
- Huzhou Central HospitalAffiliated Central Hospital Huzhou UniversityHuzhouZhejiangPeople's Republic of China
- Huzhou Central HospitalFifth Affiliated Clinical Medical College of Zhejiang Chinese Medical UniversityHuzhouZhejiangPeople's Republic of China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of HuzhouHuzhouZhejiangPeople's Republic of China
| | - Qu Zhanbo
- Huzhou Central HospitalAffiliated Central Hospital Huzhou UniversityHuzhouZhejiangPeople's Republic of China
- Huzhou Central HospitalFifth Affiliated Clinical Medical College of Zhejiang Chinese Medical UniversityHuzhouZhejiangPeople's Republic of China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of HuzhouHuzhouZhejiangPeople's Republic of China
| | - Wang Zefeng
- Huzhou UniversityHuzhouZhejiangPeople's Republic of China
| | - Han Shuwen
- Huzhou Central HospitalAffiliated Central Hospital Huzhou UniversityHuzhouZhejiangPeople's Republic of China
- Huzhou Central HospitalFifth Affiliated Clinical Medical College of Zhejiang Chinese Medical UniversityHuzhouZhejiangPeople's Republic of China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer of HuzhouHuzhouZhejiangPeople's Republic of China
- ASIR (Institute ‐ Association of intelligent systems and robotics)Rueil‐MalmaisonFrance
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14
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Lu J, Shen X, Li H, Du J. Recent advances in bacteria-based platforms for inflammatory bowel diseases treatment. EXPLORATION (BEIJING, CHINA) 2024; 4:20230142. [PMID: 39439496 PMCID: PMC11491310 DOI: 10.1002/exp.20230142] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 01/18/2024] [Indexed: 10/25/2024]
Abstract
Inflammatory bowel disease (IBD) is a recurring chronic inflammatory disease. Current treatment strategies are aimed at alleviating clinical symptoms and are associated with gastrointestinal or systemic adverse effects. New delivery strategies are needed for the treatment of IBD. Bacteria are promising biocarriers, which can produce drugs in situ and sense the gut in real time. Herein, we focus on recent studies of engineered bacteria used for IBD treatment and introduce the application of engineered bacteria in the diagnosis. On this basis, the current dilemmas and future developments of bacterial delivery systems are discussed.
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Affiliation(s)
- Jiaoying Lu
- Department of GastroenterologyThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina
| | - Xinyuan Shen
- National Key Laboratory of Advanced Drug Delivery and Release SystemsCollege of Pharmaceutical SciencesZhejiang UniversityHangzhouChina
- Department of BioengineeringUniversity of CaliforniaLos AngelesCaliforniaUSA
| | - Hongjun Li
- National Key Laboratory of Advanced Drug Delivery and Release SystemsCollege of Pharmaceutical SciencesZhejiang UniversityHangzhouChina
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangChina
- Liangzhu LaboratoryZhejiang UniversityHangzhouChina
| | - Juan Du
- Department of GastroenterologyThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina
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15
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Yang X, Nie W, Wang C, Fang Z, Shang L. Microfluidic-based multifunctional microspheres for enhanced oral co-delivery of probiotics and postbiotics. Biomaterials 2024; 308:122564. [PMID: 38581763 DOI: 10.1016/j.biomaterials.2024.122564] [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: 12/13/2023] [Revised: 03/16/2024] [Accepted: 04/01/2024] [Indexed: 04/08/2024]
Abstract
Probiotic-based therapies have shown great potential in the prevention and treatment of many diseases by positively regulating intestinal flora homeostasis. However, the efficacy of oral probiotics is severely limited due to the loss of bioactivity, short intestinal retention time, and insufficient therapeutic effect. Here, based on droplet microfluidics, we developed a hydrogel microsphere with colonic targeting and mucoadhesive capabilities as a multifunctional delivery platform, which can be used for co-delivery of probiotics (Escherichia coli Nissle 1917, EcN) and auxiliary molecules (indole-3-propionic acid, IPA), achieving synergistic therapeutic effects. In vivo studies shown that the integrated multifunctional microspheres can significantly reduce intestinal inflammation, repair intestinal barrier function, enhance probiotic colonization in the intestine, and modulate disordered intestinal flora, demonstrating enhanced therapeutic effects in a mouse model of colitis. This work reveals that microfluidic-based smart droplet microspheres can provide a versatile platform for advanced microbial therapies.
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Affiliation(s)
- Xinyuan Yang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Weimin Nie
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Chong Wang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Zhonglin Fang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
| | - Luoran Shang
- Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
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16
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Keener JE, Goh B, Yoo JS, Oh SF, Brodbelt JS. Top-Down Characterization of Bacterial Lipopolysaccharides and Lipooligosaccharides Using Activated-Electron Photodetachment Mass Spectrometry. Anal Chem 2024; 96:9151-9158. [PMID: 38758019 PMCID: PMC11384421 DOI: 10.1021/acs.analchem.4c00952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2024]
Abstract
Lipopolysaccharides (LPS) and lipooligosaccharides (LOS) are located in the outer membrane of Gram-negative bacteria and are comprised of three distinctive parts: lipid A, core oligosaccharide (OS), and O-antigen. The structure of each region influences bacterial stability, toxicity, and pathogenesis. Here, we highlight the use of targeted activated-electron photodetachment (a-EPD) tandem mass spectrometry to characterize LPS and LOS from two crucial players in the human gut microbiota, Escherichia coli Nissle and Bacteroides fragilis. a-EPD is a hybrid activation method that uses ultraviolet photoirradiation to generate charge-reduced radical ions followed by collisional activation to produce informative fragmentation patterns. We benchmark the a-EPD method for top-down characterization of triacyl LOS from E. coli R2, then focus on characterization of LPS from E. coli Nissle and B. fragilis. Notably, a-EPD affords extensive fragmentation throughout the backbone of the core OS and O-antigen regions of LPS from E. coli Nissle. This hybrid approach facilitated the elucidation of structural details for LPS from B. fragilis, revealing a putative hexuronic acid (HexA) conjugated to lipid A.
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Affiliation(s)
- James E Keener
- Department of Chemistry, University of Texas, Austin, Texas 78712, United States
| | - Byoungsook Goh
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, United States
| | - Ji-Sun Yoo
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, United States
| | - Sungwhan F Oh
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, United States
- Program in Immunology, Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts 02115, United States
| | - Jennifer S Brodbelt
- Department of Chemistry, University of Texas, Austin, Texas 78712, United States
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17
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Han M, Shen N, Tan W, Wang X, Liu Y, Liang J, Li H, Gao Z. Layer-by-layer coated probiotics with chitosan and liposomes exhibit enhanced therapeutic effects for DSS-induced colitis in mice. Int J Biol Macromol 2024; 269:132063. [PMID: 38705329 DOI: 10.1016/j.ijbiomac.2024.132063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 04/28/2024] [Accepted: 05/01/2024] [Indexed: 05/07/2024]
Abstract
Probiotic therapy has emerged as a promising approach for the treatment of gastrointestinal diseases, offering advantages in terms of safety and convenience. However, oral probiotics encounter significant challenges, including exposure to a hostile gastric environment with low pH, bile salts, elevated levels of reactive oxygen species (ROS), and damage to the protective mucus layer. These factors reduce probiotic survival rates and limit their physiological activity. To address these challenges, we developed a layer-by-layer coated probiotics with curcumin-loaded liposome and polymer. Through DSS-induced colitis mice experiments, we demonstrated that the coated probiotics exhibited an improved survival rate in the gastrointestinal tract and enhanced adhesion to the intestinal mucosa. Furthermore, multi-layered coated probiotics exhibited remarkable efficacy in alleviating colitis by efficiently repairing the gut barrier, modulating gut microbial homeostasis, and reducing bacterial motility at sites of colonic inflammation. Our innovative approach holds promise for effectively treating gastrointestinal diseases.
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Affiliation(s)
- Mengzhen Han
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Ning Shen
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Weiteng Tan
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Xiaoyang Wang
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Yuanye Liu
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Jingjing Liang
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Hongcai Li
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Zhenpeng Gao
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China.
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18
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Hu Q, Li J, Wang T, Xu X, Duan Y, Jin Y. Polyphenolic Nanoparticle-Modified Probiotics for Microenvironment Remodeling and Targeted Therapy of Inflammatory Bowel Disease. ACS NANO 2024; 18:12917-12932. [PMID: 38720520 DOI: 10.1021/acsnano.4c00830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Inflammatory bowel diseases (IBDs) refer to multifaceted disorders in the intestinal microenvironment and microbiota homeostasis. In view of the broad bioactivity and high compatibility of polyphenols, there is considerable interest in developing a polyphenol-based collaborative platform to remodel the IBD microenvironment and regulate microbiota. Here, we demonstrated the coordination assembly of nanostructured polyphenols to modify probiotics and simultaneously deliver drugs for IBD treatment. Inspired by the distinctive structure of tannic acid (TA), we fabricated nanostructured pBDT-TA by using a self-polymerizable aromatic dithiol (BDT) and TA, which exhibited excellent antioxidant and anti-inflammatory capability in vitro. We thus coated pBDT-TA and sodium alginate (SA) to the surface of Escherichia coli Nissle 1917 layer by layer to construct the collaborative platform EcN@SA-pBDT-TA. The modified probiotics showed improved resistance to oxidative and inflammatory stress, which resulted in superior colon accumulation and retention in IBD model mice. Further, EcN@SA-pBDT-TA could alleviate dextran sulfate sodium (DSS)-induced colitis by controlling the inflammatory response, repairing intestinal barriers, and modulating gut microbiota. Importantly, EcN@SA-pBDT-TA-mediated IBD drug delivery could achieve an improved therapeutic effect in DSS model mice. Given the availability and functionality of polyphenol and prebiotics, we expected that nanostructured polyphenol-modified probiotics provided a solution to develop a collaborative platform for IBD treatment.
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Affiliation(s)
- Qinglian Hu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Jingyu Li
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Tong Wang
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Xiangchi Xu
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Yuxuan Duan
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
| | - Yuanxiang Jin
- College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China
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19
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Yang H, Fan X, Mao X, Yu B, He J, Yan H, Wang J. The protective role of prebiotics and probiotics on diarrhea and gut damage in the rotavirus-infected piglets. J Anim Sci Biotechnol 2024; 15:61. [PMID: 38698473 PMCID: PMC11067158 DOI: 10.1186/s40104-024-01018-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 02/29/2024] [Indexed: 05/05/2024] Open
Abstract
Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to treat the disease, and the related vaccines have no obvious efficiency in some countries. Via analyzing the pathogenesis of rotavirus, it inducing diarrhea is mainly due to disturb enteric nervous system, destroy gut mucosal integrity, induce intracellular electrolyte imbalance, and impair gut microbiota and immunity. Many studies have already proved that prebiotics and probiotics can mitigate the damage and diarrhea induced by rotavirus infection in hosts. Based on these, the current review summarizes and discusses the effects and mechanisms of prebiotics and probiotics on rotavirus-induced diarrhea in piglets. This information will highlight the basis for the swine production utilization of prebiotics and probiotics in the prevention or treatment of rotavirus infection in the future.
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Affiliation(s)
- Heng Yang
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, No. 211, Gongpinghuimin Road, Wenjiang District, Chengdu, Sichuan Province, 611130, People's Republic of China
| | - Xiangqi Fan
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, No. 211, Gongpinghuimin Road, Wenjiang District, Chengdu, Sichuan Province, 611130, People's Republic of China
| | - Xiangbing Mao
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, No. 211, Gongpinghuimin Road, Wenjiang District, Chengdu, Sichuan Province, 611130, People's Republic of China.
| | - Bing Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, No. 211, Gongpinghuimin Road, Wenjiang District, Chengdu, Sichuan Province, 611130, People's Republic of China
| | - Jun He
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, No. 211, Gongpinghuimin Road, Wenjiang District, Chengdu, Sichuan Province, 611130, People's Republic of China
| | - Hui Yan
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, No. 211, Gongpinghuimin Road, Wenjiang District, Chengdu, Sichuan Province, 611130, People's Republic of China
| | - Jianping Wang
- Institute of Animal Nutrition, Sichuan Agricultural University, Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Key Laboratory of Animal Disease-Resistant Nutrition and Feed of China Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Disease-Resistant Nutrition of Sichuan Province, No. 211, Gongpinghuimin Road, Wenjiang District, Chengdu, Sichuan Province, 611130, People's Republic of China
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20
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Liu H, Ma J, Yang P, Geng F, Li X, Lü J, Wang Y. Comparative analysis of biofilm characterization of probiotic Escherichia coli. Front Microbiol 2024; 15:1365562. [PMID: 38559351 PMCID: PMC10978722 DOI: 10.3389/fmicb.2024.1365562] [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: 01/04/2024] [Accepted: 03/04/2024] [Indexed: 04/04/2024] Open
Abstract
Biofilms are thought to play a vital role in the beneficial effects of probiotic bacteria. However, the structure and function of probiotic biofilms are poorly understood. In this work, biofilms of Escherichia coli (E. coli) Nissle 1917 were investigated and compared with those of pathogenic and opportunistic strains (E. coli MG1655, O157:H7) using crystal violet assay, confocal laser scanning microscopy, scanning electron microscopy and FTIR microspectroscopy. The study revealed significant differences in the morphological structure, chemical composition, and spatial heterogeneity of the biofilm formed by the probiotic E. coli strain. In particular, the probiotic biofilm can secrete unique phospholipid components into the extracellular matrix. These findings provide new information on the morphology, architecture and chemical heterogeneity of probiotic biofilms. This information may help us to understand the beneficial effects of probiotics for various applications.
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Affiliation(s)
- Huiping Liu
- College of Pharmacy, Binzhou Medical University, Yantai, China
| | - Jingfang Ma
- Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
| | - Pan Yang
- College of Pharmacy, Binzhou Medical University, Yantai, China
| | - Feng Geng
- College of Pharmacy, Binzhou Medical University, Yantai, China
| | - Xueling Li
- Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Junhong Lü
- College of Pharmacy, Binzhou Medical University, Yantai, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China
| | - Yadi Wang
- College of Pharmacy, Binzhou Medical University, Yantai, China
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, China
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21
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Ingrosso MR, Gasbarrini A, Cammarota G, Ianiro G. Letter: The multifaceted role of Escherichia coli in influencing disorders of industrial populations. Aliment Pharmacol Ther 2024; 59:717-718. [PMID: 38349706 DOI: 10.1111/apt.17865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 12/23/2023] [Indexed: 02/15/2024]
Abstract
LINKED CONTENTThis article is linked to Faqerah et al papers. To view these articles, visit https://doi.org/10.1111/apt.17720 and https://doi.org/10.1111/apt.17883
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Affiliation(s)
- Maria Rosa Ingrosso
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Giovanni Cammarota
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Gianluca Ianiro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
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22
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Han M, Yang S, Song J, Gao Z. Layer-by-layer coated probiotics with chitosan and liposomes demonstrate improved stability and antioxidant properties in vitro. Int J Biol Macromol 2024; 258:128826. [PMID: 38123040 DOI: 10.1016/j.ijbiomac.2023.128826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 12/09/2023] [Accepted: 12/13/2023] [Indexed: 12/23/2023]
Abstract
Probiotics are of increasing interest for their potential health benefits, but their survival and adhesion in the harsh gastrointestinal environment remain a concern. This study explored a single-cell encapsulation technique to enhance probiotic survival and adhesion in the gastrointestinal tract. We encapsulated probiotics in curcumin-loaded liposomes, further coated them with polymers using layer-by-layer techniques. The coated probiotics were evaluated for survival in simulated gastrointestinal conditions, adhesion to colonic mucus, and scavenging of reactive oxygen species (ROS). The results showed that multi-layer encapsulation increased probiotic size at the nanoscale, enhancing their survival in simulated gastrointestinal conditions. Upon reaching the colon, the shedding of the coating coincided with probiotic proliferation. Additionally, the coated probiotics exhibited increased adhesion to colonic mucus. Moreover, the coating acted as a protective barrier for effectively scavenging reactive oxygen radicals, ensuring probiotic survival in inflammatory environments. This study combines the synergistic effects of probiotics and curcumin, underscoring the promise of single-cell encapsulation techniques in improving the efficacy of probiotics for addressing colitis-related diseases.
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Affiliation(s)
- Mengzhen Han
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China
| | - Shuang Yang
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China
| | - Jiangling Song
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China
| | - Zhenpeng Gao
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, People's Republic of China.
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23
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Yin Y, Li Z, Gao H, Zhou D, Zhu Z, Tao L, Guan W, Gao Y, Song Y, Wang M. Microfluidics-Derived Microparticles with Prebiotics and Probiotics for Enhanced In Situ Colonization and Immunoregulation of Colitis. NANO LETTERS 2024; 24:1081-1089. [PMID: 38227962 DOI: 10.1021/acs.nanolett.3c03580] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
Oral administration of probiotics orchestrates the balance between intestinal microbes and the immune response. However, effective delivery and in situ colonization are limited by the harsh environment of the gastrointestinal tract. Herein, we provide a microfluidics-derived encapsulation strategy to address this problem. A novel synergistic delivery system composed of EcN Nissle 1917 and prebiotics, including alginate sodium and inulin gel, for treating inflammatory bowel disease and colitis-associated colorectal cancer is proposed. We demonstrated that EcN@AN microparticles yielded promising gastrointestinal resistance for on-demand probiotic delivery and colon-retentive capability. EcN@AN microparticles efficiently ameliorated intestinal inflammation and modulated the gut microbiome in experimental colitis. Moreover, the prebiotic composition of EcN@AN enhanced the fermentation of relative short-chain fatty acid metabolites, a kind of postbiotics, to exert anti-inflammatory and tumor-suppressive effects in murine models. This microfluidcis-based approach for the coordinated delivery of probiotics and prebiotics may have broad implications for gastrointestinal bacteriotherapy applications.
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Affiliation(s)
- Yi Yin
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Zhun Li
- Department of General Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China
| | - Hengfei Gao
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Dongtao Zhou
- College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210023, China
| | - Zhenxing Zhu
- Department of General Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China
| | - Liang Tao
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Wenxian Guan
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
| | - Yanfeng Gao
- College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210023, China
| | - Yujun Song
- College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210023, China
| | - Meng Wang
- Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China
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24
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Maftei NM, Raileanu CR, Balta AA, Ambrose L, Boev M, Marin DB, Lisa EL. The Potential Impact of Probiotics on Human Health: An Update on Their Health-Promoting Properties. Microorganisms 2024; 12:234. [PMID: 38399637 PMCID: PMC10891645 DOI: 10.3390/microorganisms12020234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 01/17/2024] [Accepted: 01/17/2024] [Indexed: 02/25/2024] Open
Abstract
Probiotics, known to be live microorganisms, have been shown to improve or restore the gut microbiota, which in turn has been linked to improved health. It is believed that probiotics are the modern equivalent of a panacea, with claims that they may treat or prevent different diseases both in children and adults (e.g., from colic in babies to cardiovascular disease, respiratory infection, and cancer in adults). Ever since the early 2000s, probiotic-based fermented foods have had a resurgence in popularity, mostly due to claims made regarding their health benefits. Fermented foods have been associated with the prevention of irritable bowel syndrome, lactose intolerance, gastroenteritis, and obesity, but also other conditions such as chronic diarrhea, allergies, dermatitis, and bacterial and viral infections, all of which are closely related to an unhealthy lifestyle. Recent and ongoing developments in microbiome/microbiota science have given us new research directions for probiotics. The new types, mechanisms, and applications studied so far, and those currently under study, have a great potential to change scientific understanding of probiotics' nutritional applications and human health care. The expansion of fields related to the study of the microbiome and the involvement of probiotics in its improvement foreshadow an era of significant changes. An expanding range of candidate probiotic species is emerging that can address newly elucidated data-driven microbial niches and host targets. In the probiotic field, new variants of microbiome-modulating interventions are being developed, including prebiotics, symbiotics, postbiotics, microbial consortia, live biotherapeutic products, and genetically modified organisms, with renewed interest in polyphenols, fibers, and fermented foods to ensure human health. This manuscript aims to analyze recent, emerging, and anticipated trends in probiotics (sources, doses, mechanism of action, diseases for which probiotics are administered, side effects, and risks) and create a vision for the development of related areas of influence in the field.
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Affiliation(s)
- Nicoleta-Maricica Maftei
- Department of Pharmaceutical Sciences, Faculty of Medicine, and Pharmacy, “Dunărea de Jos” University, 800010 Galati, Romania; (N.-M.M.); (E.L.L.)
- Clinic Laboratory Department, Clinical Hospital of Children Hospital “Sf. Ioan”, 800487 Galati, Romania
- Research Centre in the Medical-Pharmaceutical Field, “Dunarea de Jos” University of Galati, 800010 Galati, Romania
| | - Cosmin Raducu Raileanu
- Department of Morphological and Functional Sciences, Faculty of Medicine, and Pharmacy, “Dunărea de Jos” University, 800010 Galati, Romania; (C.R.R.); (L.A.)
| | - Alexia Anastasia Balta
- Medical Department Faculty of Medicine and Pharmacy, “Dunărea de Jos” University, 800010 Galati, Romania;
| | - Lenuta Ambrose
- Department of Morphological and Functional Sciences, Faculty of Medicine, and Pharmacy, “Dunărea de Jos” University, 800010 Galati, Romania; (C.R.R.); (L.A.)
| | - Monica Boev
- Department of Pharmaceutical Sciences, Faculty of Medicine, and Pharmacy, “Dunărea de Jos” University, 800010 Galati, Romania; (N.-M.M.); (E.L.L.)
- Research Centre in the Medical-Pharmaceutical Field, “Dunarea de Jos” University of Galati, 800010 Galati, Romania
| | - Denisa Batîr Marin
- Department of Pharmaceutical Sciences, Faculty of Medicine, and Pharmacy, “Dunărea de Jos” University, 800010 Galati, Romania; (N.-M.M.); (E.L.L.)
- Research Centre in the Medical-Pharmaceutical Field, “Dunarea de Jos” University of Galati, 800010 Galati, Romania
| | - Elena Lacramioara Lisa
- Department of Pharmaceutical Sciences, Faculty of Medicine, and Pharmacy, “Dunărea de Jos” University, 800010 Galati, Romania; (N.-M.M.); (E.L.L.)
- Research Centre in the Medical-Pharmaceutical Field, “Dunarea de Jos” University of Galati, 800010 Galati, Romania
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25
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Han M, Lei W, Liang J, Li H, Hou M, Gao Z. The single-cell modification strategies for probiotics delivery in inflammatory bowel disease: A review. Carbohydr Polym 2024; 324:121472. [PMID: 37985038 DOI: 10.1016/j.carbpol.2023.121472] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/06/2023] [Accepted: 10/07/2023] [Indexed: 11/22/2023]
Abstract
Oral probiotic therapy has become an increasingly attractive method for treating various diseases, including intestinal barrier dysfunction, inflammatory bowel disease (IBD), and colorectal cancer due to its safety and convenience. However, only a few probiotics after oral gavage can survive the acidic and bile salt conditions of the gastrointestinal tract and colonize the colon to have a nutritional effect on the host. To address these challenges, encapsulation technology has been applied to protect probiotics from harsh gastrointestinal conditions, improve gut adhesion, and reduce immunogenicity. In addition, some of the functional polysaccharides are used to endow probiotics with exogenous functions as prebiotics. In this review, we systematically introduced the advancements of emerging single-cell modification strategies for probiotics in IBD applications. Additionally, we discussed the limitations and perspectives of single-cell modification strategies for probiotics. This review contributed to the development of probiotic delivery systems with higher therapeutic efficacy against colitis.
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Affiliation(s)
- Mengzhen Han
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Wenzhi Lei
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Jingjing Liang
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Hongcai Li
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Mengxin Hou
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China
| | - Zhenpeng Gao
- College of Food Science and Engineering, Northwest A&F University, 712100 Yangling, Shaanxi, China.
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26
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Hu M, Zhang T, Miao M, Li K, Luan Q, Sun G. Expectations for employing Escherichia coli Nissle 1917 in food science and nutrition. Crit Rev Food Sci Nutr 2024; 65:1802-1810. [PMID: 38189668 DOI: 10.1080/10408398.2023.2301416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
As a promising probiotic strain, Escherichia coli Nissle 1917 (EcN) has been demonstrated to confer beneficial effects on intestinal health, immune function, and pathogen prevention. Additionally, EcN has also been widely studied due to its clear genomic information, tractable gene regulation, and simple growth conditions. This review summarizes the various applications potential of EcN in food science and nutrition, including inflammation prevention, tumor-targeting therapy, antibacterial agents for food, and nutrient production with a focus on specific case studies. Moreover, we highlight the major challenges of employing EcN in food science and nutrition, including regulatory approval, stability during food processing, and consumer acceptance. Finally, we conclude with a discussion on perspectives related to employing EcN in food science and nutrition.
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Affiliation(s)
- Miaomiao Hu
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
| | - Tao Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
- International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu, China
| | - Ming Miao
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu, China
- International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, Jiangsu, China
| | - Kewen Li
- Baolingbao Biology Co., Ltd, Yucheng, Shandong, China
| | - Qingmin Luan
- Baolingbao Biology Co., Ltd, Yucheng, Shandong, China
| | - Guilian Sun
- Baolingbao Biology Co., Ltd, Yucheng, Shandong, China
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27
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Wang ZH, Zhang GY, Sun C, Ning SX, Zhou DY, Song L. Targeting DSS-induced ulcerative colitis: evaluating the therapeutic potential of WPI-stachyose conjugates. Food Funct 2024; 15:96-109. [PMID: 38047401 DOI: 10.1039/d3fo03598k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
The pursuit of food-based alternatives to conventional therapies for ulcerative colitis (UC) demands immediate attention. In prior investigations, we synthesized WPI-stachyose conjugates through the Maillard reaction, identifying them as functional prebiotics. However, their impact on in vivo regulation of gut microbiota remains inadequately explored. To bridge this gap, we delved into the therapeutic effects and mechanisms of WPI-stachyose conjugates as prebiotic-functional components in C57BL/6J mice afflicted with dextran sodium sulfate (DSS)-induced UC. The treatment involving WPI-stachyose conjugates led to significant therapeutic advancements, evident in the reduction of pro-inflammatory cytokine levels and restoration of gut microbiota composition. Noticeable enhancements were observed in UC-associated symptoms, including weight loss, colon length reduction, and tissue damage, notably improving in the treated mice. Remarkably, both the conjugates and the physical combination effectively lowered pro-inflammatory cytokines and oxidative stress, with the conjugates demonstrating enhanced effectiveness. Furthermore, the simultaneous administration of WPI-stachyose conjugates further amplified the presence of beneficial bacteria and elevated short-chain fatty acids, acknowledged for their favorable impact across various conditions. These findings underscore the potential therapeutic application of WPI-stachyose conjugates in addressing DSS-induced UC, offering insights into innovative therapeutic strategies.
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Affiliation(s)
- Zi-Han Wang
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Liaoning Province Key Laboratory for Marine Food Science and Technology, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.
| | - Guang-Yao Zhang
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Liaoning Province Key Laboratory for Marine Food Science and Technology, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.
| | - Cong Sun
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Liaoning Province Key Laboratory for Marine Food Science and Technology, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.
| | - Shu-Xin Ning
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Liaoning Province Key Laboratory for Marine Food Science and Technology, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.
| | - Da-Yong Zhou
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Liaoning Province Key Laboratory for Marine Food Science and Technology, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.
| | - Liang Song
- SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, Liaoning Province Key Laboratory for Marine Food Science and Technology, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.
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28
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Falzone L, Lavoro A, Candido S, Salmeri M, Zanghì A, Libra M. Benefits and concerns of probiotics: an overview of the potential genotoxicity of the colibactin-producing Escherichia coli Nissle 1917 strain. Gut Microbes 2024; 16:2397874. [PMID: 39229962 PMCID: PMC11376418 DOI: 10.1080/19490976.2024.2397874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 07/24/2024] [Accepted: 08/23/2024] [Indexed: 09/05/2024] Open
Abstract
Recently, the mounting integration of probiotics into human health strategies has gathered considerable attention. Although the benefits of probiotics have been widely recognized in patients with gastrointestinal disorders, immune system modulation, and chronic-degenerative diseases, there is a growing need to evaluate their potential risks. In this context, new concerns have arisen regarding the safety of probiotics as some strains may have adverse effects in humans. Among these strains, Escherichia coli Nissle 1917 (EcN) exhibited traits of concern due to a pathogenic locus in its genome that produces potentially genotoxic metabolites. As the use of probiotics for therapeutic purposes is increasing, the effects of potentially harmful probiotics must be carefully evaluated. To this end, in this narrative review article, we reported the findings of the most relevant in vitro and in vivo studies investigating the expanding applications of probiotics and their impact on human well-being addressing concerns arising from the presence of antibiotic resistance and pathogenic elements, with a focus on the polyketide synthase (pks) pathogenic island of EcN. In this context, the literature data here discussed encourages a thorough profiling of probiotics to identify potential harmful elements as done for EcN where potential genotoxic effects of colibactin, a secondary metabolite, were observed. Specifically, while some studies suggest EcN is safe for gastrointestinal health, conflicting findings highlight the need for further research to clarify its safety and optimize its use in therapy. Overall, the data here presented suggest that a comprehensive assessment of the evolving landscape of probiotics is essential to make evidence-based decisions and ensure their correct use in humans.
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Affiliation(s)
- Luca Falzone
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Alessandro Lavoro
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Saverio Candido
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
- Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, Catania, Italy
| | - Mario Salmeri
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Antonino Zanghì
- Department of Medical and Surgical Sciences and Advanced Technology 'G.F. Ingrassia', University of Catania, Catania, Italy
| | - Massimo Libra
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
- Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, Catania, Italy
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29
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Qiu J, Xiang S, Sun M, Tan M. Preparation of Polysaccharide-Protein Hydrogels with an Ultrafast Self-Healing Property as a Superior Oral Delivery System of Probiotics. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:18842-18856. [PMID: 37978937 DOI: 10.1021/acs.jafc.3c05898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2023]
Abstract
Oral administration of probiotic supplements can effectively regulate intestinal disorders. However, harsh gastrointestinal conditions greatly limit the bioavailability of probiotics. In this work, biomass-derived polysaccharide-protein hydrogels (Dex-sBSA hydrogels) were constructed as an oral probiotic delivery system. The hydrogel encapsulation significantly promoted the growth and proliferation of probiotics and protected them from gastric acid, bile salts, reactive oxygen species, and antibiotics. In vivo experiments demonstrated that the hydrogel encapsulation significantly enhanced the bioavailability of probiotics, of which the cell number in the intestine, colon, and cecum was 35 times, 8 times, and 203 times higher than the free one, respectively. Attributed to the superior ultrafast self-healing property, the Dex-sBSA hydrogel successfully prevented the probiotics from quick elimination and prolonged the retention time in the gut, providing great possibilities for colonization and proliferation. These results clearly indicate the great potential of the Dex-sBSA hydrogel as a superior oral delivery system for probiotics.
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Affiliation(s)
- Jiaqi Qiu
- State Key Lab of Marine Food Processing & Safety Control, Dalian Polytechnic University, Dalian 116034, P. R. China
- Academy of Food Interdisciplinary Science, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
- National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, P. R. China
- Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Siyuan Xiang
- State Key Lab of Marine Food Processing & Safety Control, Dalian Polytechnic University, Dalian 116034, P. R. China
- Academy of Food Interdisciplinary Science, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
- National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, P. R. China
- Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Miyao Sun
- State Key Lab of Marine Food Processing & Safety Control, Dalian Polytechnic University, Dalian 116034, P. R. China
- Academy of Food Interdisciplinary Science, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
- National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, P. R. China
- Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, P. R. China
| | - Mingqian Tan
- State Key Lab of Marine Food Processing & Safety Control, Dalian Polytechnic University, Dalian 116034, P. R. China
- Academy of Food Interdisciplinary Science, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, P. R. China
- National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, P. R. China
- Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, P. R. China
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30
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da Silva TF, Glória RDA, de Sousa TJ, Americo MF, Freitas ADS, Viana MVC, de Jesus LCL, da Silva Prado LC, Daniel N, Ménard O, Cochet MF, Dupont D, Jardin J, Borges AD, Fernandes SOA, Cardoso VN, Brenig B, Ferreira E, Profeta R, Aburjaile FF, de Carvalho RDO, Langella P, Le Loir Y, Cherbuy C, Jan G, Azevedo V, Guédon É. Comprehensive probiogenomics analysis of the commensal Escherichia coli CEC15 as a potential probiotic strain. BMC Microbiol 2023; 23:364. [PMID: 38008714 PMCID: PMC10680302 DOI: 10.1186/s12866-023-03112-4] [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: 07/17/2023] [Accepted: 11/06/2023] [Indexed: 11/28/2023] Open
Abstract
BACKGROUND Probiotics have gained attention for their potential maintaining gut and immune homeostasis. They have been found to confer protection against pathogen colonization, possess immunomodulatory effects, enhance gut barrier functionality, and mitigate inflammation. However, a thorough understanding of the unique mechanisms of effects triggered by individual strains is necessary to optimize their therapeutic efficacy. Probiogenomics, involving high-throughput techniques, can help identify uncharacterized strains and aid in the rational selection of new probiotics. This study evaluates the potential of the Escherichia coli CEC15 strain as a probiotic through in silico, in vitro, and in vivo analyses, comparing it to the well-known probiotic reference E. coli Nissle 1917. Genomic analysis was conducted to identify traits with potential beneficial activity and to assess the safety of each strain (genomic islands, bacteriocin production, antibiotic resistance, production of proteins involved in host homeostasis, and proteins with adhesive properties). In vitro studies assessed survival in gastrointestinal simulated conditions and adhesion to cultured human intestinal cells. Safety was evaluated in BALB/c mice, monitoring the impact of E. coli consumption on clinical signs, intestinal architecture, intestinal permeability, and fecal microbiota. Additionally, the protective effects of both strains were assessed in a murine model of 5-FU-induced mucositis. RESULTS CEC15 mitigates inflammation, reinforces intestinal barrier, and modulates intestinal microbiota. In silico analysis revealed fewer pathogenicity-related traits in CEC15, when compared to Nissle 1917, with fewer toxin-associated genes and no gene suggesting the production of colibactin (a genotoxic agent). Most predicted antibiotic-resistance genes were neither associated with actual resistance, nor with transposable elements. The genome of CEC15 strain encodes proteins related to stress tolerance and to adhesion, in line with its better survival during digestion and higher adhesion to intestinal cells, when compared to Nissle 1917. Moreover, CEC15 exhibited beneficial effects on mice and their intestinal microbiota, both in healthy animals and against 5FU-induced intestinal mucositis. CONCLUSIONS These findings suggest that the CEC15 strain holds promise as a probiotic, as it could modulate the intestinal microbiota, providing immunomodulatory and anti-inflammatory effects, and reinforcing the intestinal barrier. These findings may have implications for the treatment of gastrointestinal disorders, particularly some forms of diarrhea.
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Affiliation(s)
- Tales Fernando da Silva
- 1INRAE, Institut Agro, STLO, UMR1253, 65 rue de Saint Brieuc, 35042, Rennes, Cedex, France
- Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Rafael de Assis Glória
- Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Thiago Jesus de Sousa
- Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Monique Ferrary Americo
- Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Andria Dos Santos Freitas
- 1INRAE, Institut Agro, STLO, UMR1253, 65 rue de Saint Brieuc, 35042, Rennes, Cedex, France
- Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Marcus Vinicius Canário Viana
- Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Luís Cláudio Lima de Jesus
- Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | | | - Nathalie Daniel
- 1INRAE, Institut Agro, STLO, UMR1253, 65 rue de Saint Brieuc, 35042, Rennes, Cedex, France
| | - Olivia Ménard
- 1INRAE, Institut Agro, STLO, UMR1253, 65 rue de Saint Brieuc, 35042, Rennes, Cedex, France
| | - Marie-Françoise Cochet
- 1INRAE, Institut Agro, STLO, UMR1253, 65 rue de Saint Brieuc, 35042, Rennes, Cedex, France
| | - Didier Dupont
- 1INRAE, Institut Agro, STLO, UMR1253, 65 rue de Saint Brieuc, 35042, Rennes, Cedex, France
| | - Julien Jardin
- 1INRAE, Institut Agro, STLO, UMR1253, 65 rue de Saint Brieuc, 35042, Rennes, Cedex, France
| | - Amanda Dias Borges
- Department of clinical and toxicological analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Simone Odília Antunes Fernandes
- Department of clinical and toxicological analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Valbert Nascimento Cardoso
- Department of clinical and toxicological analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Bertram Brenig
- Department of Molecular Biology of Livestock, Institute of Veterinary Medicine, Georg-August Universität Göttingen, Göttingen, Germany
| | - Enio Ferreira
- Department of general pathology, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Rodrigo Profeta
- Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Flavia Figueira Aburjaile
- Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
- Veterinary school, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | | | - Philippe Langella
- Université Paris Saclay, INRAE, AgroParisTech, UMR1319, MICALIS, Jouy-en-Josas, France
| | - Yves Le Loir
- 1INRAE, Institut Agro, STLO, UMR1253, 65 rue de Saint Brieuc, 35042, Rennes, Cedex, France
| | - Claire Cherbuy
- Université Paris Saclay, INRAE, AgroParisTech, UMR1319, MICALIS, Jouy-en-Josas, France
| | - Gwénaël Jan
- 1INRAE, Institut Agro, STLO, UMR1253, 65 rue de Saint Brieuc, 35042, Rennes, Cedex, France
| | - Vasco Azevedo
- Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Éric Guédon
- 1INRAE, Institut Agro, STLO, UMR1253, 65 rue de Saint Brieuc, 35042, Rennes, Cedex, France.
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Yang X, Wang C, Wang Q, Zhang Z, Nie W, Shang L. Armored probiotics for oral delivery. SMART MEDICINE 2023; 2:e20230019. [PMID: 39188298 PMCID: PMC11235677 DOI: 10.1002/smmd.20230019] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 06/26/2023] [Indexed: 08/28/2024]
Abstract
As a kind of intestinal flora regulator, probiotics show great potential in the treatment of many diseases. However, orally delivered probiotics are often vulnerable to unfriendly gastrointestinal environments, resulting in a low survival rate and decreased therapeutic efficacy. Decorating or encapsulating probiotics with functional biomaterials has become a facile yet useful strategy, and probiotics can be given different functions by wearing different armors. This review systematically discusses the challenges faced by oral probiotics and the research progress of armored probiotics delivery systems. We focus on how various functional armors help probiotics overcome different obstacles and achieve efficient delivery. We also introduce the applications of armor probiotics in disease treatment and analyze the future trends of developing advanced probiotics-based therapies.
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Affiliation(s)
- Xinyuan Yang
- Zhongshan‐Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co‐laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan UniversityShanghaiChina
| | - Chong Wang
- Zhongshan‐Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co‐laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan UniversityShanghaiChina
| | - Qiao Wang
- Zhongshan‐Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co‐laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan UniversityShanghaiChina
| | - Zhuohao Zhang
- Zhongshan‐Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co‐laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan UniversityShanghaiChina
| | - Weimin Nie
- Key Laboratory of Smart Drug DeliverySchool of PharmacyFudan UniversityShanghaiChina
| | - Luoran Shang
- Zhongshan‐Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics, the International Co‐laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan UniversityShanghaiChina
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Chathuranga K, Shin Y, Uddin MB, Paek J, Chathuranga WAG, Seong Y, Bai L, Kim H, Shin JH, Chang YH, Lee JS. The novel immunobiotic Clostridium butyricum S-45-5 displays broad-spectrum antiviral activity in vitro and in vivo by inducing immune modulation. Front Immunol 2023; 14:1242183. [PMID: 37881429 PMCID: PMC10595006 DOI: 10.3389/fimmu.2023.1242183] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Accepted: 09/20/2023] [Indexed: 10/27/2023] Open
Abstract
Clostridium butyricum is known as a probiotic butyric acid bacterium that can improve the intestinal environment. In this study, we isolated a new strain of C. butyricum from infant feces and evaluated its physiological characteristics and antiviral efficacy by modulating the innate immune responses in vitro and in vivo. The isolated C. butyricum S-45-5 showed typical characteristics of C. butyricum including bile acid resistance, antibacterial ability, and growth promotion of various lactic acid bacteria. As an antiviral effect, C. butyricum S-45-5 markedly reduced the replication of influenza A virus (PR8), Newcastle Disease Virus (NDV), and Herpes Simplex Virus (HSV) in RAW264.7 cells in vitro. This suppression can be explained by the induction of antiviral state in cells by the induction of antiviral, IFN-related genes and secretion of IFNs and pro-inflammatory cytokines. In vivo, oral administration of C. butyricum S-45-5 exhibited prophylactic effects on BALB/c mice against fatal doses of highly pathogenic mouse-adapted influenza A subtypes (H1N1, H3N2, and H9N2). Before challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed increased levels of IFN-β, IFN-γ, IL-6, and IL-12 in serum, the small intestine, and bronchoalveolar lavage fluid (BALF), which correlated with observed prophylactic effects. Interestingly, after challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed reduced levels of pro-inflammatory cytokines and relatively higher levels of anti-inflammatory cytokines at day 7 post-infection. Taken together, these findings suggest that C. butyricum S-45-5 plays an antiviral role in vitro and in vivo by inducing an antiviral state and affects immune modulation to alleviate local and systemic inflammatory responses caused by influenza virus infection. Our study provides the beneficial effects of the new C. butyricum S-45-5 with antiviral effects as a probiotic.
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Affiliation(s)
- Kiramage Chathuranga
- College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea
| | - Yeseul Shin
- Access to Genetic Resources and Benefit-Sharing (ABS) Research Support Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Md Bashir Uddin
- College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea
- Department of Medicine, Sylhet Agricultural University, Sylhet, Bangladesh
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United States
| | - Jayoung Paek
- Access to Genetic Resources and Benefit-Sharing (ABS) Research Support Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | | | - Yebin Seong
- College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea
| | - Lu Bai
- Access to Genetic Resources and Benefit-Sharing (ABS) Research Support Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Hongik Kim
- Research and Development Division, Vitabio, Inc., Daejeon, Republic of Korea
| | - Jeong Hwan Shin
- Department of Laboratory Medicine, Inje University College of Medicine, Busan, Republic of Korea
| | - Young-Hyo Chang
- Access to Genetic Resources and Benefit-Sharing (ABS) Research Support Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
| | - Jong-Soo Lee
- College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea
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Lei P, Yu H, Ma J, Du J, Fang Y, Yang Q, Zhang K, Luo L, Jin L, Wu W, Sun D. Cell membrane nanomaterials composed of phospholipids and glycoproteins for drug delivery in inflammatory bowel disease: A review. Int J Biol Macromol 2023; 249:126000. [PMID: 37532186 DOI: 10.1016/j.ijbiomac.2023.126000] [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: 05/30/2023] [Revised: 07/21/2023] [Accepted: 07/24/2023] [Indexed: 08/04/2023]
Abstract
Inflammatory bowel disease (IBD) is a serious chronic intestinal disorder with an increasing global incidence. However, current treatment strategies, such as anti-inflammatory drugs and probiotics, have limitations in terms of safety, stability, and effectiveness. The emergence of targeted nanoparticles has revolutionized IBD treatment by enhancing the biological properties of drugs and promoting efficiency and safety. Unlike synthetic nanoparticles, cell membrane nanomaterials (CMNs) consist primarily of biological macromolecules, including phospholipids, proteins, and sugars. CMNs include red blood cell membranes, macrophage membranes, and leukocyte membranes, which possess abundant glycoprotein receptors and ligands on their surfaces, allowing for the formation of cell-to-cell connections with other biological macromolecules. Consequently, they exhibit superior cell affinity, evade immune responses, and target inflammation effectively, making them ideal material for targeted delivery of IBD therapies. This review explores various CMNs delivery systems for IBD treatment. However, due to the complexity and harsh nature of the intestinal microenvironment, the lack of flexibility or loss of selectivity poses challenges in designing single CMNs delivery strategies. Therefore, we propose a hierarchically programmed delivery modality that combines CMNs with pH, charge, ROS and ligand-modified responsive nanoparticles. This approach significantly improves delivery efficiency and points the way for future research in this area.
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Affiliation(s)
- Pengyu Lei
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Haiyang Yu
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Jiahui Ma
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Jiao Du
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Yimeng Fang
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Qinsi Yang
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China
| | - Kun Zhang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400044, China
| | - Li Luo
- Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong 523059, China
| | - Libo Jin
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China.
| | - Wei Wu
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400044, China.
| | - Da Sun
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China.
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Chen H, Lei P, Ji H, Ma J, Fang Y, Yu H, Du J, Qu L, Yang Q, Luo L, Zhang K, Wu W, Jin L, Sun D. Escherichia coli Nissle 1917 ghosts alleviate inflammatory bowel disease in zebrafish. Life Sci 2023; 329:121956. [PMID: 37473802 DOI: 10.1016/j.lfs.2023.121956] [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: 05/15/2023] [Revised: 07/14/2023] [Accepted: 07/17/2023] [Indexed: 07/22/2023]
Abstract
Escherichia coli Nissle 1917 (EcN) has become a research hotspot in inflammatory bowel disease (IBD). It has a strong targeting effect on the colon, and has some therapeutic effect on inflammatory bowel disease. EcN is prepared into EcN ghosts, which also retain EcN's biological characteristics. Consequently, EcN ghosts are used for drug delivery. This study evaluated the safety and efficacy of EcN ghosts as carriers of drugs for treating IBD in zebrafish. Caco-2 cell adhesion experiments and zebrafish intestinal adhesion experiments demonstrated that EcN ghosts was highly adherent to the intestine. Additionally, oral administration of EcN ghosts attenuated dextran sulfate sodium-induced IBD symptoms by inhibiting neutrophil chemotaxis and reactive oxygen species production in larval zebrafish. Because of the unique biological functions of EcN ghosts, it may serve as a strategy for future targeted drug delivery in IBD treatment.
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Affiliation(s)
- Haojie Chen
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Pengyu Lei
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Hao Ji
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Jiahui Ma
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Yimeng Fang
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Haiyang Yu
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Jiao Du
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China
| | - Linkai Qu
- College of Veterinary Medicine, Jilin University, Changchun 130062, China
| | - Qinsi Yang
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China
| | - Li Luo
- Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523059, China
| | - Kun Zhang
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400044, China
| | - Wei Wu
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400044, China.
| | - Libo Jin
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China.
| | - Da Sun
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China.
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Campagnoli LIM, Varesi A, Barbieri A, Marchesi N, Pascale A. Targeting the Gut-Eye Axis: An Emerging Strategy to Face Ocular Diseases. Int J Mol Sci 2023; 24:13338. [PMID: 37686143 PMCID: PMC10488056 DOI: 10.3390/ijms241713338] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/20/2023] [Accepted: 08/26/2023] [Indexed: 09/10/2023] Open
Abstract
The human microbiota refers to a large variety of microorganisms (bacteria, viruses, and fungi) that live in different human body sites, including the gut, oral cavity, skin, and eyes. In particular, the presence of an ocular surface microbiota with a crucial role in maintaining ocular surface homeostasis by preventing colonization from pathogen species has been recently demonstrated. Moreover, recent studies underline a potential association between gut microbiota (GM) and ocular health. In this respect, some evidence supports the existence of a gut-eye axis involved in the pathogenesis of several ocular diseases, including age-related macular degeneration, uveitis, diabetic retinopathy, dry eye, and glaucoma. Therefore, understanding the link between the GM and these ocular disorders might be useful for the development of new therapeutic approaches, such as probiotics, prebiotics, symbiotics, or faecal microbiota transplantation through which the GM could be modulated, thus allowing better management of these diseases.
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Affiliation(s)
| | - Angelica Varesi
- Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy;
| | - Annalisa Barbieri
- Department of Drug Sciences, Unit of Pharmacology, University of Pavia, 27100 Pavia, Italy; (A.B.); (N.M.)
| | - Nicoletta Marchesi
- Department of Drug Sciences, Unit of Pharmacology, University of Pavia, 27100 Pavia, Italy; (A.B.); (N.M.)
| | - Alessia Pascale
- Department of Drug Sciences, Unit of Pharmacology, University of Pavia, 27100 Pavia, Italy; (A.B.); (N.M.)
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Jans M, Kolata M, Blancke G, Ciers M, Dohlman AB, Kusakabe T, Sze M, Thiran A, Berx G, Tejpar S, van Loo G, Iliev ID, Remaut H, Vereecke L. Colibactin-induced genotoxicity and colorectal cancer exacerbation critically depends on adhesin-mediated epithelial binding. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.08.16.553526. [PMID: 37645947 PMCID: PMC10462063 DOI: 10.1101/2023.08.16.553526] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/31/2023]
Abstract
Various bacteria are suggested to contribute to colorectal cancer (CRC) development, including pks+ E. coli which produce the genotoxin colibactin that induces characteristic mutational signatures in host epithelial cells. It remains unclear how the highly unstable colibactin molecule is able to access host epithelial cells and its DNA to cause harm. Using the microbiota-dependent ZEB2-transgenic mouse model of invasive CRC, we found that pks+ E. coli drives CRC exacerbation and tissue invasion in a colibactin-dependent manner. Using isogenic mutant strains, we further demonstrate that CRC exacerbation critically depends on expression of the E. coli type-1 pilus adhesin FimH and the F9-pilus adhesin FmlH. Blocking bacterial adhesion using a pharmacological FimH inhibitor attenuates colibactin-mediated genotoxicity and CRC exacerbation. Together, we show that the oncogenic potential of pks+ E. coli critically depends on bacterial adhesion to host epithelial cells and is critically mediated by specific bacterial adhesins. Adhesin-mediated epithelial binding subsequently allows production of the genotoxin colibactin in close proximity to host epithelial cells, which promotes DNA damage and drives CRC development. These findings present promising therapeutic avenues for the development of anti-adhesive therapies aiming at mitigating colibactin-induced DNA damage and inhibiting the initiation and progression of CRC, particularly in individuals at risk for developing CRC.
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Fu J, Zong X, Jin M, Min J, Wang F, Wang Y. Mechanisms and regulation of defensins in host defense. Signal Transduct Target Ther 2023; 8:300. [PMID: 37574471 PMCID: PMC10423725 DOI: 10.1038/s41392-023-01553-x] [Citation(s) in RCA: 55] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 04/11/2023] [Accepted: 06/26/2023] [Indexed: 08/15/2023] Open
Abstract
As a family of cationic host defense peptides, defensins are mainly synthesized by Paneth cells, neutrophils, and epithelial cells, contributing to host defense. Their biological functions in innate immunity, as well as their structure and activity relationships, along with their mechanisms of action and therapeutic potential, have been of great interest in recent years. To highlight the key research into the role of defensins in human and animal health, we first describe their research history, structural features, evolution, and antimicrobial mechanisms. Next, we cover the role of defensins in immune homeostasis, chemotaxis, mucosal barrier function, gut microbiota regulation, intestinal development and regulation of cell death. Further, we discuss their clinical relevance and therapeutic potential in various diseases, including infectious disease, inflammatory bowel disease, diabetes and obesity, chronic inflammatory lung disease, periodontitis and cancer. Finally, we summarize the current knowledge regarding the nutrient-dependent regulation of defensins, including fatty acids, amino acids, microelements, plant extracts, and probiotics, while considering the clinical application of such regulation. Together, the review summarizes the various biological functions, mechanism of actions and potential clinical significance of defensins, along with the challenges in developing defensins-based therapy, thus providing crucial insights into their biology and potential clinical utility.
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Affiliation(s)
- Jie Fu
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, China
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, Hangzhou, Zhejiang Province, China
| | - Xin Zong
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, China
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, Hangzhou, Zhejiang Province, China
| | - Mingliang Jin
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, China
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, Hangzhou, Zhejiang Province, China
| | - Junxia Min
- The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China
| | - Fudi Wang
- The Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China.
- The First Affiliated Hospital, Basic Medical Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.
| | - Yizhen Wang
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, China.
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, Hangzhou, Zhejiang Province, China.
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Mishra G, Singh P, Molla M, Yimer YS, Dinda SC, Chandra P, Singh BK, Dagnew SB, Assefa AN, Ewunetie A. Harnessing the potential of probiotics in the treatment of alcoholic liver disorders. Front Pharmacol 2023; 14:1212742. [PMID: 37361234 PMCID: PMC10287977 DOI: 10.3389/fphar.2023.1212742] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 05/22/2023] [Indexed: 06/28/2023] Open
Abstract
In the current scenario, prolonged consumption of alcohol across the globe is upsurging an appreciable number of patients with the risk of alcohol-associated liver diseases. According to the recent report, the gut-liver axis is crucial in the progression of alcohol-induced liver diseases, including steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Despite several factors associated with alcoholic liver diseases, the complexity of the gut microflora and its great interaction with the liver have become a fascinating area for researchers due to the high exposure of the liver to free radicals, bacterial endotoxins, lipopolysaccharides, inflammatory markers, etc. Undoubtedly, alcohol-induced gut microbiota imbalance stimulates dysbiosis, disrupts the intestinal barrier function, and trigger immune as well as inflammatory responses which further aggravate hepatic injury. Since currently available drugs to mitigate liver disorders have significant side effects, hence, probiotics have been widely researched to alleviate alcohol-associated liver diseases and to improve liver health. A broad range of probiotic bacteria like Lactobacillus, Bifidobacteria, Escherichia coli, Sacchromyces, and Lactococcus are used to reduce or halt the progression of alcohol-associated liver diseases. Several underlying mechanisms, including alteration of the gut microbiome, modulation of intestinal barrier function and immune response, reduction in the level of endotoxins, and bacterial translocation, have been implicated through which probiotics can effectively suppress the occurrence of alcohol-induced liver disorders. This review addresses the therapeutic applications of probiotics in the treatment of alcohol-associated liver diseases. Novel insights into the mechanisms by which probiotics prevent alcohol-associated liver diseases have also been elaborated.
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Affiliation(s)
- Garima Mishra
- Pharmaceutical Chemistry Unit, Department of Pharmacy, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Pradeep Singh
- Pharmaceutical Chemistry Unit, Department of Pharmacy, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Mulugeta Molla
- Pharmacology and Toxicology Unit, Department of Pharmacy, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Yohannes Shumet Yimer
- Social Pharmacy Unit, Department of Pharmacy, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | | | - Phool Chandra
- Department of Pharmacology, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, India
| | | | - Samuel Berihun Dagnew
- Clinical Pharmacy Unit, Department of Pharmacy, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Abraham Nigussie Assefa
- Social Pharmacy Unit, Department of Pharmacy, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Amien Ewunetie
- Pharmacology and Toxicology Unit, Department of Pharmacy, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
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Wang T, Yin Q, Huang HY, Wang Z, Song H, Luo X. Probiotic Escherichia coli Nissle 1917 propelled micro-robot with pH sensitivity for hypoxia targeted intestinal tumor therapy. Colloids Surf B Biointerfaces 2023; 225:113277. [PMID: 36996630 DOI: 10.1016/j.colsurfb.2023.113277] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 03/17/2023] [Accepted: 03/21/2023] [Indexed: 03/30/2023]
Abstract
Poor drug penetration in hypoxia area of solid tumor is a big challenge for intestinal tumor therapy and thus it is crucial to develop an effective strategy to overcome this challenge. Compared with other bacteria used for construction of hypoxia targeted bacteria micro-robot, the Escherichia coli Nissle 1917 (EcN) bacteria are nonpathogenic Gram-negative probiotic and can especially target and identify the signal molecules in the hypoxic region of tumor, and thus, in this study, we choose EcN to construct a bacteria propelled micro-robot for targeting intestinal tumor therapy. Firstly, the MSNs@DOX with average diameter of 200 nm were synthesized and conjugated with EcN bacteria using EDC/NHS chemical crosslinking method to construct a EcN propelled micro-robot. The motility of micro-robot was then evaluated and the motion velocity of EcN-pMSNs@DOX was 3.78 µm/s. Compared with pMSNs@DOX without EcN driven, EcN bacteria propelled micro-robot transported much more pMSNs@DOX into the inner of HCT-116 3D multicellular tumor spheroids. However, the EcN bacteria are non-intracelluar bacteria which lead to the micro-robot can not directly enter into tumor cells. Therefore, we utilized acid-labile linkers of cis-aconitic amido bone to link EcN with MSNs@DOX nanoparticles to achieve the pH sensitive separation of EcN with MSNs@DOX from the micro-robot. At 4 h of incubation, the isolated MSNs@DOX began to enter into the tumor cells through CLSM observation. In vitro live/dead staining results show that EcN-pMSNs@DOX induced much more cell death than pMSNs@DOX at 24 and 48 h of incubation with HCT-116 tumor cells in acid culture media (pH 5.3). For the validation of the therapeutic efficacy of the micro-robot for intestinal tumor, we established the HCT-116 subcutaneous transplantation tumor model. After 28 days of treatment, EcN-pMSNs@DOX dramatically inhibit tumor growth with tumor volume was around 689 mm3, induce much more tumor tissues necrosis and apoptosis. Finally, the toxicity of this micro-robot was investigated by pathological analysis the liver and heart tissues. We expect that the pH sensitive EcN propelled micro-robot here we constructed may be a safe and feasible strategy for intestinal tumor therapy.
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Hu Q, Yu L, Zhai Q, Zhao J, Tian F. Anti-Inflammatory, Barrier Maintenance, and Gut Microbiome Modulation Effects of Saccharomyces cerevisiae QHNLD8L1 on DSS-Induced Ulcerative Colitis in Mice. Int J Mol Sci 2023; 24:ijms24076721. [PMID: 37047694 PMCID: PMC10094816 DOI: 10.3390/ijms24076721] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 03/24/2023] [Accepted: 03/29/2023] [Indexed: 04/07/2023] Open
Abstract
The use of probiotics has been considered as a new therapy option for ulcerative colitis (UC), and yeast has recently received widespread recommendation for human health. In this study, the probiotic characteristics of four yeast strains, Saccharomyces boulardii CNCMI-745, Kluyveromyces marxianus QHBYC4L2, Saccharomyces cerevisiae QHNLD8L1, and Debaryomyces hansenii QSCLS6L3, were evaluated in vitro; their ability to ameliorate dextran sulfate sodium (DSS)-induced colitis was investigated. Among these, S. cerevisiae QHNLD8L1 protected against colitis, which was reflected by increased body weight, colon length, histological injury relief, decreased gut inflammation markers, and intestinal barrier restoration. The abundance of the pathogenic bacteria Escherichia–Shigella and Enterococcaceae in mice with colitis decreased after S. cerevisiae QHNLD8L1 treatment. Moreover, S. cerevisiae QHNLD8L1 enriched beneficial bacteria Lactobacillus, Faecalibaculum, and Butyricimonas, enhanced carbon metabolism and fatty acid biosynthesis function, and increased short chain fatty acid (SCFAs) production. Taken together, our results indicate the great potential of S. cerevisiae QHNLD8L1 supplementation for the prevention and alleviation of UC.
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Affiliation(s)
- Qianjue Hu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Leilei Yu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Fengwei Tian
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
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Chen H, Lei P, Ji H, Yang Q, Peng B, Ma J, Fang Y, Qu L, Li H, Wu W, Jin L, Sun D. Advances in Escherichia coli Nissle 1917 as a customizable drug delivery system for disease treatment and diagnosis strategies. Mater Today Bio 2023; 18:100543. [PMID: 36647536 PMCID: PMC9840185 DOI: 10.1016/j.mtbio.2023.100543] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 01/02/2023] [Accepted: 01/05/2023] [Indexed: 01/07/2023] Open
Abstract
With the in-depth and comprehensive study of bacteria and their related ecosystems in the human body, bacterial-based drug delivery system has become an emerging biomimetic platform that can retain the innate biological functions. Benefiting from its good biocompatibility and ideal targeting ability as a biological carrier, Escherichia coli Nissle 1917 (ECN) has been focused on the treatment strategies of inflammatory bowel disease and tumor. The advantage of a bacterial carrier is that it can express exogenous protein while also acting as a natural capsule by releasing drug slowly as a result of its own colonization impact. In order to survive in harsh environments such as the digestive tract and tumor microenvironment, ECN can be modified or genetically engineered to enhance its function and host adaptability. The adoption of ECN carries or expresses drugs which are essential for accurate diagnosis and treatment. This review briefly describes the properties of ECN, the relationship between ECN and inflammation and tumor, and the strategy of using surface modification and genetic engineering to modify ECN as a delivery carrier for disease treatment.
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Affiliation(s)
- Haojie Chen
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, 325035, China
| | - Pengyu Lei
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, 325035, China
| | - Hao Ji
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, 325035, China
| | - Qinsi Yang
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325000, China
| | - Bo Peng
- Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325000, China
| | - Jiahui Ma
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, 325035, China
| | - Yimeng Fang
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, 325035, China
| | - Linkai Qu
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, 325035, China
- College of Life Sciences, Jilin Agricultural University, Changchun, 130118, China
| | - Hua Li
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China
| | - Wei Wu
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China
| | - Libo Jin
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, 325035, China
- Wenzhou City and WenZhouOuTai Medical Laboratory Co.,Ltd Joint Doctoral Innovation Station, Wenzhou Association for Science and Technology, Wenzhou, 325000, China
| | - Da Sun
- Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, 325035, China
- Wenzhou City and Kunlong Technology Co., Ltd., Joint Doctoral Innovation Station, Wenzhou Association for Science and Technology, Wenzhou, 325000, China
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Bondegaard PW, Torp AM, Guerra P, Kristensen KA, Christfort JF, Krogfelt KA, Nielsen LH, Zor K, Boisen A, Mortensen MS, Bahl MI, Licht TR. Delivery of E. coli Nissle to the mouse gut by mucoadhesive microcontainers does not improve its competitive ability against strains linked to ulcerative colitis. FEMS Microbiol Lett 2023; 370:fnad110. [PMID: 37863838 PMCID: PMC10612143 DOI: 10.1093/femsle/fnad110] [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: 07/18/2023] [Revised: 10/02/2023] [Accepted: 10/19/2023] [Indexed: 10/22/2023] Open
Abstract
For patients with ulcerative colitis (UC), administration of the probiotic E. coli Nissle (EcN) holds promise for alleviation of disease symptoms. The mechanisms are unclear, but it has been hypothesised that a capacity of the probiotic to outcompete potentially detrimental UC-associated E. coli strains plays an important role. However, this could previously not be confirmed in a mouse model of competition between EcN and two UC-associated strains, as reported by Petersen et al. 2011. In the present study, we re-evaluated the idea, hypothesising that delivery of EcN by a micro device dosing system (microcontainers), designed for delivery into the intestinal mucus, could support colonisation and confer a competition advantage compared to classical oral dosing. Six groups of mice were pre-colonised with one of two UC-associated E. coli strains followed by oral delivery of EcN, either in capsules containing microcontainers with freeze-dried EcN powder, capsules containing freeze-dried EcN powder, or as a fresh sucrose suspension. Co-colonisation between the probiotic and the disease-associated strains was observed regardless of dosing method, and no competition advantages linked to microcontainer delivery were identified within this setup. Other approaches are thus needed if the competitive capacity of EcN in the gut should be improved.
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Affiliation(s)
- Pi Westi Bondegaard
- National Food Institute, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark
| | - Anders Meyer Torp
- National Food Institute, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark
| | - Priscila Guerra
- National Food Institute, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark
| | - Katja Ann Kristensen
- National Food Institute, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark
| | | | - Karen Angeliki Krogfelt
- Department of Science and Environment, Molecular and Medical Biology, Roskilde University, Roskilde, 4000, Denmark
| | - Line Hagner Nielsen
- Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark
| | - Kinga Zor
- Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark
| | - Anja Boisen
- Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark
| | | | - Martin Iain Bahl
- National Food Institute, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark
| | - Tine Rask Licht
- National Food Institute, Technical University of Denmark, Kgs. Lyngby, 2800, Denmark
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43
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Zheng L, Duan SL, Dai YC, Wu SC. Role of adherent invasive Escherichia coli in pathogenesis of inflammatory bowel disease. World J Clin Cases 2022; 10:11671-11689. [PMID: 36405271 PMCID: PMC9669839 DOI: 10.12998/wjcc.v10.i32.11671] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 09/04/2022] [Accepted: 10/11/2022] [Indexed: 02/05/2023] Open
Abstract
Gut microbiota imbalances play an important role in inflammatory bowel disease (IBD), but no single pathogenic microorganism critical to IBD that is specific to the IBD terminal ileum mucosa or can invade intestinal epithelial cells has been found. Invasive Escherichia coli (E. coli) adhesion to macrophages is considered to be closely related to the pathogenesis of inflammatory bowel disease. Further study of the specific biological characteristics of adherent invasive E. coli (AIEC) may contribute to a further understanding of IBD pathogenesis. This review explores the relationship between AIEC and the intestinal immune system, discusses the prevalence and relevance of AIEC in Crohn's disease and ulcerative colitis patients, and describes the relationship between AIEC and the disease site, activity, and postoperative recurrence. Finally, we highlight potential therapeutic strategies to attenuate AIEC colonization in the intestinal mucosa, including the use of phage therapy, antibiotics, and anti-adhesion molecules. These strategies may open up new avenues for the prevention and treatment of IBD in the future.
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Affiliation(s)
- Lie Zheng
- Department of Gastroenterology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an 322000, Shaanxi Province, China
| | - Sheng-Lei Duan
- Department of Gastroenterology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an 322000, Shaanxi Province, China
| | - Yan-Cheng Dai
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Shi-Cheng Wu
- Department of Proctology, Gansu Academy of Traditional Chinese Medicine, Gansu Hospital of Traditional Chinese Medicine, Lanzhou 730050, Gansu Province, China
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44
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Zhang T, Zhang W, Feng C, Kwok LY, He Q, Sun Z. Stronger gut microbiome modulatory effects by postbiotics than probiotics in a mouse colitis model. NPJ Sci Food 2022; 6:53. [PMID: 36379940 PMCID: PMC9666507 DOI: 10.1038/s41538-022-00169-9] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 10/21/2022] [Indexed: 11/17/2022] Open
Abstract
Probiotics are increasingly used as adjunctive therapy to manage gastrointestinal diseases, such as ulcerative colitis. However, probiotic use has posed some safety concerns. Thus, postbiotics are proposed as alternatives to probiotics in clinical applications. However, no study has directly compared the clinical benefits of probiotics and postbiotics. This study compared the beneficial effect of postbiotics and probiotics derived from the strain, Bifidobacterium adolescentis B8598, in a dextran sulfate sodium (DSS)-induced experimental colitis mouse model. Four groups of mice (n = 7 per group) were included in this work: Control (received water plus saline), DSS (received DSS without postbiotic/probiotic), Postbiotic (received DSS plus postbiotic), and Probiotic (received DSS plus probiotic). Our results showed that intragastric administration of both probiotic and postbiotic ameliorated colitis, reflected by decreased histology scores in Postbiotic and Probiotic groups compared with DSS group (P < 0.05). The fecal microbiota alpha diversity was not significantly affected by DSS-, postbiotic, or probiotic treatment. However, the postbiotic treatment showed stronger effects on modulating the fecal microbiota beta diversity, composition, and metagenomic potential than the probiotic treatment. Overall, our findings suggested that probiotics and postbiotics had similar ability to improve disease phenotype but had distinct ability to regulate the gut microbiota and metabolic pathways in the context of ulcerative colitis. In view of the smaller safety concern of postbiotics compared with probiotics and its stronger modulatory effect on the host gut microbiota, we propose that postbiotics are to be considered for use as next-generation biotherapeutics in managing ulcerative colitis or even other diseases.
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Affiliation(s)
- Tao Zhang
- grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China
| | - Weiqin Zhang
- grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China
| | - Cuijiao Feng
- grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China
| | - Lai-Yu Kwok
- grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China
| | - Qiuwen He
- grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China
| | - Zhihong Sun
- grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China ,grid.411638.90000 0004 1756 9607Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, 010018 Hohhot, P. R. China
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Orlova EG, Maslennikova IL, Pospelova JS, Starčič Erjavec M, Loginova NP, Troinich YN, Kuznetsova MV. The effect of Escherichia coli ŽP strain with a conjugation-based colicin E7 delivery on growth performance, hematological, biochemical, and histological parameters, gut microbiota, and nonspecific immunity of broilers. Can J Microbiol 2022; 68:687-702. [PMID: 36121064 DOI: 10.1139/cjm-2022-0044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The Escherichia coli ŽP strain (ŽP) was constructed based on the known probiotic E. coli strain Nissle 1917. It was genetically modified to carry the colicin E7 synthesis gene encoding DNase on a conjugative plasmid and the colicin E7 immunity gene in the chromosome. The aim of this study was to evaluate the effects of the daily ŽP per oral administration (5 × 108 or 5 × 1010 CFU per bird) on the growth performance, hematological, biochemical, histological parameters, gut microbiota, and nonspecific immunity of the 4-24 days old broilers. The ŽP administration increased the abundance of genera Bacillus, Butyrivibrio, and Clostridium and did not influence the weight gain of 4-16 days old broilers. The biochemical parameters were within normal ranges for poultry in experimental and control groups. The ŽP administration had no effect on the erythrocyte numbers, hemoglobin and immunoglobulin Y concentrations, but significantly increased the serum lysozyme concentration, leukocyte numbers, and reactive oxygen species production by phagocytes compared with the control group. It did not cause inflammatory changes in intestinal mucosa, Peyer's patches, and spleen. Thus, the ŽP had no detrimental effects on broiler health and could be an efficient probiotic for the broiler colibacillosis prophylaxis.
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Affiliation(s)
- E G Orlova
- Institute of Ecology and Genetics of Microorganisms, Ural Branch, Russian Academy of Science, Perm, Russia
| | - I L Maslennikova
- Institute of Ecology and Genetics of Microorganisms, Ural Branch, Russian Academy of Science, Perm, Russia
| | - J S Pospelova
- Institute of Ecology and Genetics of Microorganisms, Ural Branch, Russian Academy of Science, Perm, Russia
| | | | | | | | - M V Kuznetsova
- Institute of Ecology and Genetics of Microorganisms, Ural Branch, Russian Academy of Science, Perm, Russia.,Perm State Medical University, Perm, Russia
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46
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Dong Y, Xu T, Xiao G, Hu Z, Chen J. Opportunities and challenges for synthetic biology in the therapy of inflammatory bowel disease. Front Bioeng Biotechnol 2022; 10:909591. [PMID: 36032720 PMCID: PMC9399643 DOI: 10.3389/fbioe.2022.909591] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 07/15/2022] [Indexed: 11/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a complex, chronic intestinal inflammatory disorder that primarily includes Crohn’s disease (CD) and ulcerative colitis (UC). Although traditional antibiotics and immunosuppressants are known as the most effective and commonly used treatments, some limitations may be expected, such as limited efficacy in a small number of patients and gut flora disruption. A great many research studies have been done with respect to the etiology of IBD, while the composition of the gut microbiota is suggested as one of the most influential factors. Along with the development of synthetic biology and the continuing clarification of IBD etiology, broader prospects for novel approaches to IBD therapy could be obtained. This study presents an overview of the currently existing treatment options and possible therapeutic targets at the preclinical stage with respect to microbial synthesis technology in biological therapy. This study is highly correlated to the following topics: microbiota-derived metabolites, microRNAs, cell therapy, calreticulin, live biotherapeutic products (LBP), fecal microbiota transplantation (FMT), bacteriophages, engineered bacteria, and their functional secreted synthetic products for IBD medical implementation. Considering microorganisms as the main therapeutic component, as a result, the related clinical trial stability, effectiveness, and safety analysis may be the major challenges for upcoming research. This article strives to provide pharmaceutical researchers and developers with the most up-to-date information for adjuvant medicinal therapies based on synthetic biology.
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Affiliation(s)
- Yumeng Dong
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
- Suzhou U-Synbio Co., Ltd., Suzhou, China
| | - Tiangang Xu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Guozheng Xiao
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Ziyan Hu
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Jingyu Chen
- College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
- *Correspondence: Jingyu Chen,
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