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Antoine T, Béduneau A, Chrétien C, Cornu R, Bonnefoy F, Moulari B, Perruche S, Pellequer Y. Clinically relevant cell culture model of inflammatory bowel diseases for identification of new therapeutic approaches. Int J Pharm 2025; 669:125062. [PMID: 39653295 DOI: 10.1016/j.ijpharm.2024.125062] [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: 11/08/2024] [Revised: 12/04/2024] [Accepted: 12/06/2024] [Indexed: 12/16/2024]
Abstract
Inflammatory Bowel Diseases (IDB) are chronic disorders characterized by gut inflammation, mucosal damage, increased epithelial permeability and altered mucus layer. No accurate in vitro model exists to simulate these characteristics. In this context, drug development for IBD or intestinal inflammation requires in vivo evaluations to verify treatments efficacy. A new model with altered mucus layer composition; altered epithelial permeability and pro-inflammatory crosstalk between immune and epithelial cells will be developed to enhance in vitro models for studying IBD treatments. The effects of dextran sulfate sodium and/or lipopolysaccharides on intestinal permeability, cytokines synthesis (IL-6, IL-8, TNF-α and IL-1β), mucins (MUC2, MUC5AC) and tight junction proteins expression (Claudin-1, ZO-1 and Occludin) were investigated in a tri-coculture model combining differentiated Caco-2/HT29-MTX cells and THP-1 cells. Two anti-inflammatory agents were evaluated to assess the model's therapeutic strategy applicability (corticoids and pro-resolving factors). Two in vitro models have been developed. The first model, characterized by increased permeability of the epithelial layer and subsequent secretion of inflammatory cytokines, can reproduce the different phases of inflammation, and enables the evaluation of preventive treatments. The second model simulates the acute phase of inflammation and allows for the assessment of curative treatments. Both models demonstrated reversibility when treated with betamethasone and pro-resolving factors. These in vitro models are valuable for selecting therapeutic agents prior to their application in in vivo models. They enable the assessment of agents' anti-inflammatory effects and their ability to permeate the inflamed epithelial layer and interact with immune cells.
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Affiliation(s)
- Thomas Antoine
- Université de Franche-Comté, EFS, INSERM, UMR RIGHT, LabEx LipSTIC (ANR-11- LABX-0021), F-25000 Besançon, France
| | - Arnaud Béduneau
- Université de Franche-Comté, EFS, INSERM, UMR RIGHT, LabEx LipSTIC (ANR-11- LABX-0021), F-25000 Besançon, France
| | - Claire Chrétien
- Université de Franche-Comté, EFS, INSERM, UMR RIGHT, LabEx LipSTIC (ANR-11- LABX-0021), F-25000 Besançon, France
| | - Raphaël Cornu
- Université de Franche-Comté, EFS, INSERM, UMR RIGHT, LabEx LipSTIC (ANR-11- LABX-0021), F-25000 Besançon, France
| | - Francis Bonnefoy
- Université de Franche-Comté, EFS, INSERM, UMR RIGHT, LabEx LipSTIC (ANR-11- LABX-0021), F-25000 Besançon, France; MED'INN'Pharma, F-25000 Besançon, France
| | - Brice Moulari
- Université de Franche-Comté, EFS, INSERM, UMR RIGHT, LabEx LipSTIC (ANR-11- LABX-0021), F-25000 Besançon, France
| | - Sylvain Perruche
- Université de Franche-Comté, EFS, INSERM, UMR RIGHT, LabEx LipSTIC (ANR-11- LABX-0021), F-25000 Besançon, France; MED'INN'Pharma, F-25000 Besançon, France
| | - Yann Pellequer
- Université de Franche-Comté, EFS, INSERM, UMR RIGHT, LabEx LipSTIC (ANR-11- LABX-0021), F-25000 Besançon, France.
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Méndez López LF, González Llerena JL, Vázquez Rodríguez JA, Medellín Guerrero AB, González Martínez BE, Solís Pérez E, López-Cabanillas Lomelí M. Dietary Modulation of the Immune System. Nutrients 2024; 16:4363. [PMID: 39770983 PMCID: PMC11676904 DOI: 10.3390/nu16244363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/15/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
Recent insights into the influence of nutrition on immune system components have driven the development of dietary strategies targeting the prevention and management of major metabolic-inflammatory diseases. This review summarizes the bidirectional relationship between nutrition and immunocompetence, beginning with an overview of immune system components and their functions. It examines the effects of nutritional status, dietary patterns, and food bioactives on systemic inflammation, immune cell populations, and lymphoid tissues, as well as their associations with infectious and chronic disease pathogenesis. The mechanisms by which key nutrients influence immune constituents are delineated, focusing on vitamins A, D, E, C, and B, as well as minerals including zinc, iron, and selenium. Also highlighted are the immunomodulatory effects of polyunsaturated fatty acids as well as bioactive phenolic compounds and probiotics, given their expanding relevance. Each section addresses the implications of nutritional and nutraceutical interventions involving these nutrients within the broader context of major infectious, metabolic, and inflammatory diseases. This review further underscores that, while targeted nutrient supplementation can effectively restore immune function to optimal levels, caution is necessary in certain cases, as it may increase morbidity in specific diseases. In other instances, dietary counseling should be integrated to ensure that therapeutic goals are achieved safely and effectively.
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Affiliation(s)
| | | | | | | | | | | | - Manuel López-Cabanillas Lomelí
- Universidad Autónoma de Nuevo León, Facultad de Salud Pública y Nutrición, Centro de Investigación en Nutrición y Salud Pública, Monterrey 64460, México; (L.F.M.L.)
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Atta SA, Fahmy ZH, Selim EAH, Aboushousha T, Mostafa RR. Effect of linex treatment on IFN-γ and IL-4 in mice infected with Trichinella. BMC Infect Dis 2024; 24:1360. [PMID: 39609767 PMCID: PMC11603642 DOI: 10.1186/s12879-024-10202-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 11/11/2024] [Indexed: 11/30/2024] Open
Abstract
Trichinellosis is a zoonotic, foodborne parasitic infection causing muscle damage. This study investigated the potential therapeutic effects of the commercially available probiotic treatment Linex, both alone and in combination with Albendazole (ALB), on the intestinal and muscular stages of Trichinella spiralis infection in mice, assessing outcomes through parasitological, immunological, and histopathological measures. This study is the first to demonstrate the synergistic effect of combining the commercially available probiotic Linex with Albendazole for trichinellosis treatment. By enhancing both parasitological and immunological outcomes, this combined therapy not only significantly reduces parasite burden but also modulates the immune response, shifting it toward a protective Th1 profile. In parasitological terms, the highest adult and larval count reduction was observed in combined Linex and Albendazole treatment (100%, 97.7%) respectively. Lesser percentage of reduction were recorded in Linex alone therapy (43.2%, 88.4%) respectively. Histopathologically there was amelioration of the inflammatory cellular infiltration in all treated groups with best results in combined Linex and Albendazole treatment. Immunologically, serum IFN-γ levels increased significantly in all treated groups with highest levels in combined Linex and Albendazole treatment, while IL-4 and IL-13 level decreased significantly in all treated groups with best results observed in Linex alone treatment. To conclude; combined Linex and Albendazole treatment of mice infected with T. spirals could ameliorate the infection and improve the immune response.
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Affiliation(s)
- Shimaa Attia Atta
- Department of Immunology, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Zeinab H Fahmy
- Department of Parasitology, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Eman A H Selim
- Department of Parasitology, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Tarek Aboushousha
- Department of Pathology, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Reham Refaat Mostafa
- Departments of Medical Parasitology Faculty of Medicine, Cairo University, Cairo, Egypt.
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Bao HF, She CH, Hou CC, Ji DN, Hu D, Zou J, Shen Y, Jian LL, Cai JF, Ye JF, Luo D, Ma HF, Guan JL. PLK1-activating IFI16-STING-TBK1 pathway induces apoptosis of intestinal epithelial cells in patients with intestinal Behçet's syndrome. FEBS J 2024; 291:3432-3453. [PMID: 38676954 DOI: 10.1111/febs.17147] [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: 07/21/2023] [Revised: 12/28/2023] [Accepted: 04/15/2024] [Indexed: 04/29/2024]
Abstract
Inflammatory signals from immunological cells may cause damage to intestinal epithelial cells (IECs), resulting in intestinal inflammation and tissue impairment. Interferon-γ-inducible protein 16 (IFI16) was reported to be involved in the pathogenesis of Behçet's syndrome (BS). This study aimed to investigate how inflammatory cytokines released by immunological cells and IFI16 participate in the pathogenesis of intestinal BS. RNA sequencing and real-time quantitative PCR (qPCR) showed that the positive regulation of tumor necrosis factor-α (TNF-α) production in peripheral blood mononuclear cells (PBMCs) of intestinal BS patients may be related to the upregulation of polo like kinase 1 (PLK1) in PBMCs (P = 0.012). The plasma TNF-α protein level in intestinal BS was significantly higher than in healthy controls (HCs; P = 0.009). PBMCs of intestinal BS patients and HCs were co-cultured with human normal IECs (NCM460) to explore the interaction between immunological cells and IECs. Using IFI16 knockdown, PBMC-NCM460 co-culture, TNF-α neutralizing monoclonal antibody (mAb), stimulator of interferon genes (STING) agonist 2'3'-cGAMP, and the PLK1 inhibitor SBE 13 HCL, we found that PLK1 promotes the secretion of TNF-α from PBMCs of intestinal BS patients, which causes overexpression of IFI16 and induces apoptosis of IECs via the STING-TBK1 pathway. The expressions of IFI16, TNF-α, cleaved caspase 3, phosphorylated STING (pSTING) and phosphorylated tank binding kinase 1 (pTBK1) in the intestinal ulcer tissue of BS patients were significantly higher than that of HCs (all P < 0.05). PLK1 in PBMCs of intestinal BS patients increased TNF-α secretion, inducing IEC apoptosis via activation of the IFI16-STING-TBK1 pathway. PLK1 and the IFI16-STING-TBK1 pathway may be new therapeutic targets for intestinal BS.
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Affiliation(s)
- Hua-Fang Bao
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Chun-Hui She
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Cheng-Cheng Hou
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Da-Nian Ji
- Department of Gastrointestinal Endoscopy, Huadong Hospital, Fudan University, Shanghai, China
| | - Dan Hu
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Jun Zou
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Yan Shen
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Lei-Lei Jian
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Jian-Fei Cai
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Jing-Fen Ye
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Dan Luo
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Hai-Fen Ma
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
| | - Jian-Long Guan
- Department of Rheumatology and Immunology, Huadong Hospital, Fudan University, Shanghai, China
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Yang H, Lin Y, Ma Y, Li J, Li J, Huo Z, Yang P, Zhang C. Screening Probiotics for Anti- Helicobacter pylori and Investigating the Effect of Probiotics on Patients with Helicobacter pylori Infection. Foods 2024; 13:1851. [PMID: 38928794 PMCID: PMC11202727 DOI: 10.3390/foods13121851] [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: 04/25/2024] [Revised: 05/21/2024] [Accepted: 05/29/2024] [Indexed: 06/28/2024] Open
Abstract
Probiotics are natural microbial agents with beneficial properties such as bacteriostatic and anti-infective properties. Lactobacillus plantarum Q21, Q25 and QA85, were isolated from the Chinese specialty fermented food "Jiangshui" and proved to be highly resistant to Helicobacter pylori (p < 0.0001). In vitro results showed that Q21, Q25 and QA85 strongly inhibited H. pylori and could specifically co-aggregate H. pylori in vitro (more than 56%). Strains have the potential to adhere to cells and hinder H. pylori colonization (p < 0.0001). To assess the anti-H. pylori efficacy of strains in vivo, volunteers were recruited and a self-controlled study of probiotic intervention was conducted. Compared to pre-probiotics, volunteers who took Q21, Q25 and QA85 for 1 month showed significant improvement in discomfort, a significant reduction in GSRS scores (p < 0.05), and modulation of inflammatory response (p < 0.05). Q21, Q25 and QA85 resulted in a decreasing trend of H. pylori load in volunteers (454.30 ± 327.00 vs. 328.35 ± 237.19, p = 0.06). However, the strains were not significantly effective in modulating the imbalance of the gut microbiota caused by H. pylori infection. In addition, strains affect metabolic pathways by increasing the levels of O-Phosphoethanolamine and other related metabolites, which may ameliorate associated symptoms. Therefore, Lactobacillus plantarum Q21, Q25 and QA85 can be regarded as a candidate probiotic preparation that exerts direct or indirect anti-H. pylori effects by inhibiting H. pylori activity and colonization, reducing inflammation and discomfort, maintaining homeostasis in the internal environment, affecting the metabolic pathways and repairing the body barrier. They can play a role in relieving H. pylori infection.
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Affiliation(s)
- Hui Yang
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
| | - Yang Lin
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou 730000, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China
| | - Yuchan Ma
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
| | - Jiaru Li
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
| | - Junxiang Li
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou 730000, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China
| | - Zeqi Huo
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou 730000, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China
| | - Pingrong Yang
- School of Pharmacy, Lanzhou University, Lanzhou 730000, China
| | - Chunjiang Zhang
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou 730000, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China
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Emanuel E, Arifuzzaman M, Artis D. Epithelial-neuronal-immune cell interactions: Implications for immunity, inflammation, and tissue homeostasis at mucosal sites. J Allergy Clin Immunol 2024; 153:1169-1180. [PMID: 38369030 PMCID: PMC11070312 DOI: 10.1016/j.jaci.2024.02.004] [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: 01/23/2024] [Revised: 02/13/2024] [Accepted: 02/14/2024] [Indexed: 02/20/2024]
Abstract
The epithelial lining of the respiratory tract and intestine provides a critical physical barrier to protect host tissues against environmental insults, including dietary antigens, allergens, chemicals, and microorganisms. In addition, specialized epithelial cells communicate directly with hematopoietic and neuronal cells. These epithelial-immune and epithelial-neuronal interactions control host immune responses and have important implications for inflammatory conditions associated with defects in the epithelial barrier, including asthma, allergy, and inflammatory bowel diseases. In this review, we discuss emerging research that identifies the mechanisms and impact of epithelial-immune and epithelial-neuronal cross talk in regulating immunity, inflammation, and tissue homeostasis at mucosal barrier surfaces. Understanding the regulation and impact of these pathways could provide new therapeutic targets for inflammatory diseases at mucosal sites.
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Affiliation(s)
- Elizabeth Emanuel
- Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY; Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine, New York, NY
| | - Mohammad Arifuzzaman
- Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY
| | - David Artis
- Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY; Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine, New York, NY; Friedman Center for Nutrition and Inflammation, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY; Allen Discovery Center for Neuroimmune Interactions, New York, NY; Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY.
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Liu T, Gu J, Fu C, Su L. Three-Dimensional Scaffolds for Intestinal Cell Culture: Fabrication, Utilization, and Prospects. TISSUE ENGINEERING. PART B, REVIEWS 2024; 30:158-175. [PMID: 37646409 DOI: 10.1089/ten.teb.2023.0124] [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: 09/01/2023]
Abstract
The intestine is a visceral organ that integrates absorption, metabolism, and immunity, which is vulnerable to external stimulus. Researchers in the fields such as food science, immunology, and pharmacology have committed to developing appropriate in vitro intestinal cell models to study the intestinal absorption and metabolism mechanisms of various nutrients and drugs, or pathogenesis of intestinal diseases. In the past three decades, the intestinal cell models have undergone a significant transformation from conventional two-dimensional cultures to three-dimensional (3D) systems, and the achievements of 3D cell culture have been greatly contributed by the fabrication of different scaffolds. In this review, we first introduce the developing trend of existing intestinal models. Then, four types of scaffolds, including Transwell, hydrogel, tubular scaffolds, and intestine-on-a-chip, are discussed for their 3D structure, composition, advantages, and limitations in the establishment of intestinal cell models. Excitingly, some of the in vitro intestinal cell models based on these scaffolds could successfully mimic the 3D structure, microenvironment, mechanical peristalsis, fluid system, signaling gradients, or other important aspects of the original human intestine. Furthermore, we discuss the potential applications of the intestinal cell models in drug screening, disease modeling, and even regenerative repair of intestinal tissues. This review presents an overview of state-of-the-art scaffold-based cell models within the context of intestines, and highlights their major advances and applications contributing to a better knowledge of intestinal diseases. Impact statement The intestine tract is crucial in the absorption and metabolism of nutrients and drugs, as well as immune responses against external pathogens or antigens in a complex microenvironment. The appropriate experimental cell model in vitro is needed for in-depth studies of intestines, due to the limitation of animal models in dynamic control and real-time assessment of key intestinal physiological and pathological processes, as well as the "R" principles in laboratory animal experiments. Three-dimensional (3D) scaffold-based cell cultivation has become a developing tendency because of the superior cell proliferation and differentiation and more physiologically relevant environment supported by the customized 3D scaffolds. In this review, we summarize four types of up-to-date 3D cell culture scaffolds fabricated by various materials and techniques for a better recapitulation of some essential physiological and functional characteristics of original intestines compared to conventional cell models. These emerging 3D intestinal models have shown promising results in not only evaluating the pharmacokinetic characteristics, security, and effectiveness of drugs, but also studying the pathological mechanisms of intestinal diseases at cellular and molecular levels. Importantly, the weakness of the representative 3D models for intestines is also discussed.
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Affiliation(s)
- Tiange Liu
- Department of Food Science and Technology, National University of Singapore (Suzhou) Research Institute, Suzhou, China
| | - Jia Gu
- Department of Food Science and Technology, National University of Singapore (Suzhou) Research Institute, Suzhou, China
| | - Caili Fu
- Department of Food Science and Technology, National University of Singapore (Suzhou) Research Institute, Suzhou, China
| | - Lingshan Su
- Department of Food Science and Technology, National University of Singapore (Suzhou) Research Institute, Suzhou, China
- Department of Food Science and Technology, National University of Singapore, Singapore, Singapore
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Xu Y, Zhang F, Mu G, Zhu X. Effect of lactic acid bacteria fermentation on cow milk allergenicity and antigenicity: A review. Compr Rev Food Sci Food Saf 2024; 23:e13257. [PMID: 38284611 DOI: 10.1111/1541-4337.13257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 09/22/2023] [Accepted: 10/02/2023] [Indexed: 01/30/2024]
Abstract
Cow milk is a major allergenic food. The potential prevention and treatment effects of lactic acid bacteria (LAB)-fermented dairy products on allergic symptoms have garnered considerable attention. Cow milk allergy (CMA) is mainly attributed to extracellular and/or cell envelope proteolytic enzymes with hydrolysis specificity. Numerous studies have demonstrated that LAB prevents the risk of allergies by modulating the development and regulation of the host immune system. Specifically, LAB and its effectors can enhance intestinal barrier function and affect immune cells by interfering with humoral and cellular immunity. Fermentation hydrolysis of allergenic epitopes is considered the main mechanism of reducing CMA. This article reviews the linear epitopes of allergens in cow milk and the effect of LAB on these allergens and provides insight into the means of predicting allergenic epitopes by conventional laboratory analysis methods combined with molecular simulation. Although LAB can reduce CMA in several ways, the mechanism of action remains partially clarified. Therefore, this review additionally attempts to summarize the main mechanism of LAB fermentation to provide guidance for establishing an effective preventive and treatment method for CMA and serve as a reference for the screening, research, and application of LAB-based intervention.
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Affiliation(s)
- Yunpeng Xu
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning, P. R. China
| | - Feifei Zhang
- Liaoning Ocean and Fisheries Science Research Institute, Dalian, Liaoning, P. R. China
| | - Guangqing Mu
- Dalian Key Laboratory of Functional Probiotics, Dalian, Liaoning, P. R. China
| | - Xuemei Zhu
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning, P. R. China
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Coelho-Rocha ND, de Jesus LCL, Barroso FAL, da Silva TF, Ferreira E, Gonçalves JE, Dos Santos Martins F, de Oliveira Carvalho RD, Barh D, Azevedo VADC. Evaluation of Probiotic Properties of Novel Brazilian Lactiplantibacillus plantarum Strains. Probiotics Antimicrob Proteins 2023; 15:160-174. [PMID: 36028786 DOI: 10.1007/s12602-022-09978-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/15/2022] [Indexed: 01/20/2023]
Abstract
Beneficial effects of Lactiplantibacillus plantarum strains have been widely reported. Knowing that the effects of probiotic bacteria are strain-dependent, this study aimed to characterize the probiotic properties and investigate the gastrointestinal protective effects of nine novel L. plantarum strains isolated from Bahia, Brazil. The probiotic functionality was first evaluated in vitro by characterizing bile salt and acidic tolerance, antibacterial activity, and adhesion to Caco-2 cells. Antibiotic resistance profile, mucin degradation, and hemolytic activity assays were also performed to evaluate safety features. In vivo analyses were conducted to investigate the anti-inflammatory effects of the strains on a mouse model of 5-Fluorouracil-induced mucositis. Our results suggest that the used L. plantarum strains have good tolerance to bile salts and low pH and can inhibit commonly gastrointestinal pathogens. Lp2 and Lpl1 strains also exhibited high adhesion rates to Caco-2 cells (13.64 and 9.05%, respectively). Phenotypical resistance to aminoglycosides, vancomycin, and tetracycline was observed for most strains. No strain showed hemolytic or mucolytic activity. Seven strains had a protective effect against histopathological and inflammatory damage induced by 5-FU. Gene expression analysis of inflammatory markers showed that five strains upregulated interleukin 10 (Il10), while four downregulated both interleukin 6 (Il6) and interleukin 1b (Il1b). Additionally, all strains reduced eosinophilic and neutrophilic infiltration; however, they could not prevent weight loss or reduced liquid/ food intake. Altogether, our study suggests these Brazilian L. plantarum strains present good probiotic characteristics and safety levels for future applications and can be therapeutically adjuvant alternatives to prevent/treat intestinal mucositis.
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Affiliation(s)
- Nina Dias Coelho-Rocha
- Department of Genetics, Ecology, and Evolution, Biological Sciences Institute, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, 31270-901, Brazil
| | - Luís Cláudio Lima de Jesus
- Department of Genetics, Ecology, and Evolution, Biological Sciences Institute, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, 31270-901, Brazil
| | - Fernanda Alvarenga Lima Barroso
- Department of Genetics, Ecology, and Evolution, Biological Sciences Institute, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, 31270-901, Brazil
| | - Tales Fernando da Silva
- Department of Genetics, Ecology, and Evolution, Biological Sciences Institute, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, 31270-901, Brazil
| | - Enio Ferreira
- Department of General Pathology, Biological Sciences Institute, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, 31270-901, Brazil
| | - José Eduardo Gonçalves
- Department of Pharmaceutic Products, Pharmacy Faculty, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, 31270-901, Brazil
| | - Flaviano Dos Santos Martins
- Department of Microbiology, Biological Sciences Institute, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, 31270-901, Brazil
| | - Rodrigo Dias de Oliveira Carvalho
- Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-909, Brazil
| | - Debmalya Barh
- Institute of Integrative Omics and Applied Biotechnology (IIOAB), West Bengal, Nonakuri, Purba Medinipur, 721172, India
| | - Vasco Ariston de Carvalho Azevedo
- Department of Genetics, Ecology, and Evolution, Biological Sciences Institute, Federal University of Minas Gerais, Minas Gerais, Belo Horizonte, 31270-901, Brazil.
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Liu S, Zhang S, Wang Y, Lu S, Han S, Liu Y, Jiang H, Wang C, Liu H. Dietary Sodium Butyrate Improves Intestinal Health of Triploid Oncorhynchus mykiss Fed a Low Fish Meal Diet. BIOLOGY 2023; 12:biology12020145. [PMID: 36829424 PMCID: PMC9952962 DOI: 10.3390/biology12020145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/08/2023] [Accepted: 01/14/2023] [Indexed: 01/20/2023]
Abstract
This study aimed to determine the effects of dietary sodium butyrate (NaB) on the growth and gut health of triploid Oncorhynchus mykiss juveniles (8.86 ± 0.36 g) fed a low fish meal diet for 8 weeks, including the inflammatory response, histomorphology, and the composition and functional prediction of microbiota. Five isonitrogenous and isoenergetic practical diets (15.00% fish meal and 21.60% soybean meal) were supplemented with 0.00% (G1), 0.10% (G2), 0.20% (G3), 0.30% (G4), and 0.40% NaB (G5), respectively. After the feeding trial, the mortality for G3 challenged with Aeromonas salmonicida for 7 days was lower than that for G1 and G5. The optimal NaB requirement for triploid O. mykiss based on weight gain rate (WGR) and the specific growth rate (SGR) was estimated to be 0.22% and 0.20%, respectively. The activities of intestinal digestive enzymes increased in fish fed a NaB diet compared to G1 (p < 0.05). G1 also showed obvious signs of inflammation, but this inflammation was significantly alleviated with dietary NaB supplementation. In comparison, G3 exhibited a more complete intestinal mucosal morphology. Dietary 0.20% NaB may play an anti-inflammatory role by inhibiting the NF-κB-P65 inflammatory signaling pathway. Additionally, the relative abundance of probiotics was altered by dietary NaB. In conclusion, dietary 0.20% NaB improved the intestinal health of triploid O. mykiss fed a low fish meal diet.
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Affiliation(s)
- Siyuan Liu
- Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China
- College of Fisheries and Life Science, Dalian Ocean University, Dalian 116023, China
| | - Shuze Zhang
- Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China
- College of Animal Science and Technology, Northeast Agricultural University, Harbin 150006, China
| | - Yaling Wang
- Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China
- College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China
| | - Shaoxia Lu
- Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China
| | - Shicheng Han
- Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China
| | - Yang Liu
- Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China
| | - Haibo Jiang
- College of Animal Science, Guizhou University, Guiyang 550025, China
| | - Chang’an Wang
- Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China
- Correspondence: (C.W.); (H.L.); Tel.: +86-13936508461 (C.W.); +86-13796050776 (H.L.)
| | - Hongbai Liu
- Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China
- Correspondence: (C.W.); (H.L.); Tel.: +86-13936508461 (C.W.); +86-13796050776 (H.L.)
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11
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Mazziotta C, Tognon M, Martini F, Torreggiani E, Rotondo JC. Probiotics Mechanism of Action on Immune Cells and Beneficial Effects on Human Health. Cells 2023; 12:184. [PMID: 36611977 PMCID: PMC9818925 DOI: 10.3390/cells12010184] [Citation(s) in RCA: 257] [Impact Index Per Article: 128.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 12/12/2022] [Accepted: 12/29/2022] [Indexed: 01/03/2023] Open
Abstract
Immune cells and commensal microbes in the human intestine constantly communicate with and react to each other in a stable environment in order to maintain healthy immune activities. Immune system-microbiota cross-talk relies on a complex network of pathways that sustain the balance between immune tolerance and immunogenicity. Probiotic bacteria can interact and stimulate intestinal immune cells and commensal microflora to modulate specific immune functions and immune homeostasis. Growing evidence shows that probiotic bacteria present important health-promoting and immunomodulatory properties. Thus, the use of probiotics might represent a promising approach for improving immune system activities. So far, few studies have been reported on the beneficial immune modulatory effect of probiotics. However, many others, which are mainly focused on their metabolic/nutritional properties, have been published. Therefore, the mechanisms behind the interaction between host immune cells and probiotics have only been partially described. The present review aims to collect and summarize the most recent scientific results and the resulting implications of how probiotic bacteria and immune cells interact to improve immune functions. Hence, a description of the currently known immunomodulatory mechanisms of probiotic bacteria in improving the host immune system is provided.
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Affiliation(s)
- Chiara Mazziotta
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
- Center for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 64/b, Fossato di Mortara Street, 44121 Ferrara, Italy
| | - Mauro Tognon
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
| | - Fernanda Martini
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
- Center for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 64/b, Fossato di Mortara Street, 44121 Ferrara, Italy
- Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy
| | - Elena Torreggiani
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
| | - John Charles Rotondo
- Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy
- Center for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 64/b, Fossato di Mortara Street, 44121 Ferrara, Italy
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12
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Kiššová Z, Tkáčiková Ľ, Mudroňová D, Bhide MR. Immunomodulatory Effect of Lactobacillus reuteri ( Limosilactobacillus reuteri) and Its Exopolysaccharides Investigated on Epithelial Cell Line IPEC-J2 Challenged with Salmonella Typhimurium. LIFE (BASEL, SWITZERLAND) 2022; 12:life12121955. [PMID: 36556320 PMCID: PMC9788328 DOI: 10.3390/life12121955] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/16/2022] [Accepted: 11/18/2022] [Indexed: 11/24/2022]
Abstract
The gastrointestinal tract is the largest and most complex component of the immune system. Each component influences the production and regulation of cytokines secreted by intestinal epithelial cells. The aim of this study was to see how the probiotic strain Limosilactobacillus reuteri L26 and its exopolysaccharide (EPS) affect porcine intestinal-epithelial cells IPEC-J2 infected with Salmonella Typhimurium. The results revealed that Salmonella infection up-regulated all studied pro-inflammatory cytokines such as TNF-α, IL-8, IL-6 and TLR4, TLR5 signaling pathways, while decreasing the expression of TGF-β. An immunosuppressive activity was found in EPS-treated wells, since the transcriptional levels of the studied pro-inflammatory cytokines were not increased, and the pretreatment with EPS was even able to attenuate up-regulated pro-inflammatory genes induced by Salmonella infection. However, there was a significant increase in the expression of mRNA levels of IL-8 and TNF-α in L26-treated cells, although this up-regulation was suppressed in the case of pretreatment. The immunoregulatory function of L. reuteri was also confirmed by the increased level of mRNA expression for TGF-β, a known immunosuppressive mediator. The most relevant finding of this ex vivo study was a case of immunity modulation, where the probiotic strain L. reuteri stimulated the innate immune-cell response which displayed both anti- and pro-inflammatory activities, and modulated the expression of TLRs in the IPEC-J2 cell line. Our findings also revealed that the pretreatment of cells with either EPS or live lactobacilli prior to infection has a suppressive effect on the inflammatory response induced by Salmonella Typhimurium.
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Affiliation(s)
- Zuzana Kiššová
- Institute of Immunology, University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia
- Correspondence: (Z.K.); (Ľ.T.)
| | - Ľudmila Tkáčiková
- Institute of Immunology, University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia
- Correspondence: (Z.K.); (Ľ.T.)
| | - Dagmar Mudroňová
- Institute of Immunology, University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia
| | - Mangesh R. Bhide
- Laboratory of Biomedical Microbiology and Immunology, University of Veterinary Medicine and Pharmacy in Kosice, 041 81 Kosice, Slovakia
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13
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Saha UB, Saroj SD. Lactic acid bacteria: prominent player in the fight against human pathogens. Expert Rev Anti Infect Ther 2022; 20:1435-1453. [PMID: 36154442 DOI: 10.1080/14787210.2022.2128765] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The human microbiome is a unique repository of diverse bacteria. Over 1000 microbial species reside in the human gut, which predominantly influences the host's internal environment and plays a significant role in host health. Lactic acid bacteria have long been employed for multiple purposes, ranging from food to medicines. Lactobacilli, which are often used in commercial food fermentation, have improved to the point that they might be helpful in medical applications. AREAS COVERED This review summarises various clinical and experimental evidence on efficacy of lactobacilli in treating a wide range of infections. Both laboratory based and clinical studies have been discussed. EXPERT OPINION Lactobacilli are widely accepted as safe biological treatments and host immune modulators (GRAS- Generally regarded as safe) by the US Food and Drug Administration and Qualified Presumption of Safety. Understanding the molecular mechanisms of lactobacilli in the treatment and pathogenicity of bacterial infections can help with the prediction and development of innovative therapeutics aimed at pathogens which have gained resistance to antimicrobials. To formulate effective lactobacilli based therapy significant research on the effectiveness of different lactobacilli strains and its association with demographic distribution is required. Also, the side effects of such therapy needs to be evaluated.
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Affiliation(s)
- Ujjayni B Saha
- Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Symbiosis Knowledge Village, Lavale, Pune, India
| | - Sunil D Saroj
- Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Symbiosis Knowledge Village, Lavale, Pune, India
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14
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Xu Z, Jiang N, Xiao Y, Yuan K, Wang Z. The role of gut microbiota in liver regeneration. Front Immunol 2022; 13:1003376. [PMID: 36389782 PMCID: PMC9647006 DOI: 10.3389/fimmu.2022.1003376] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 10/12/2022] [Indexed: 12/02/2022] Open
Abstract
The liver has unique regeneration potential, which ensures the continuous dependence of the human body on hepatic functions. As the composition and function of gut microbiota has been gradually elucidated, the vital role of gut microbiota in liver regeneration through gut-liver axis has recently been accepted. In the process of liver regeneration, gut microbiota composition is changed. Moreover, gut microbiota can contribute to the regulation of the liver immune microenvironment, thereby modulating the release of inflammatory factors including IL-6, TNF-α, HGF, IFN-γ and TGF-β, which involve in different phases of liver regeneration. And previous research have demonstrated that through enterohepatic circulation, bile acids (BAs), lipopolysaccharide, short-chain fatty acids and other metabolites of gut microbiota associate with liver and may promote liver regeneration through various pathways. In this perspective, by summarizing gut microbiota-derived signaling pathways that promote liver regeneration, we unveil the role of gut microbiota in liver regeneration and provide feasible strategies to promote liver regeneration by altering gut microbiota composition.
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Affiliation(s)
- Zhe Xu
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Nan Jiang
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yuanyuan Xiao
- Department of Obstetrics and Gynecology, West China Second Hospital of Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China
- *Correspondence: Zhen Wang, ; Kefei Yuan, ; Yuanyuan Xiao,
| | - Kefei Yuan
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- *Correspondence: Zhen Wang, ; Kefei Yuan, ; Yuanyuan Xiao,
| | - Zhen Wang
- Department of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- Laboratory of Liver Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
- *Correspondence: Zhen Wang, ; Kefei Yuan, ; Yuanyuan Xiao,
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15
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Lacticaseibacillus casei Strain Shirota Modulates Macrophage-Intestinal Epithelial Cell Co-Culture Barrier Integrity, Bacterial Sensing and Inflammatory Cytokines. Microorganisms 2022; 10:microorganisms10102087. [PMID: 36296363 PMCID: PMC9607601 DOI: 10.3390/microorganisms10102087] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 10/03/2022] [Accepted: 10/06/2022] [Indexed: 11/06/2022] Open
Abstract
Probiotic bacteria modulate macrophage immune inflammatory responses, with functional cytokine responses determined by macrophage subset polarisation, stimulation and probiotic strain. Mucosal macrophages exhibit subset functional heterogeneity but are organised in a 3-dimensional tissue, over-laid by barrier epithelial cells. This study aimed to investigate the effects of the probiotic Lacticaseibacillus casei strain Shirota (LcS) on macrophage-epithelial cell cytokine responses, pattern recognition receptor (PRR) expression and LPS responses and the impacts on barrier integrity. THP-1-derived M1 and M2 subset macrophages were co-cultured in a transwell system with differentiated Caco-2 epithelial cells in the presence or absence of enteropathogenic LPS. Both Caco-2 cells in monoculture and macrophage co-culture were assayed for cytokines, PRR expression and barrier integrity (TEER and ZO-1) by RT-PCR, ELISA, IHC and electrical resistance. Caco-2 monocultures expressed distinct cytokine profiles (IL-6, IL-8, TNFα, endogenous IL-10), PRRs and barrier integrity, determined by inflammatory context (TNFα or IL-1β). In co-culture, LcS rescued ZO-1 and TEER in M2/Caco-2, but not M1/Caco-2. LcS suppressed TLR2, TLR4, MD2 expression in both co-cultures and differentially regulated NOD2, TLR9, Tollip and cytokine secretion. In conclusion, LcS selectively modulates epithelial barrier integrity, pathogen sensing and inflammatory cytokine profile; determined by macrophage subset and activation status.
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16
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Ghasemi M, Bakhshi B, Khashei R, Soudi S. Mesoporous silica nano-adjuvant triggers pro-inflammatory responses in Caco-2/peripheral blood mononuclear cell (PBMC) co-cultures. Nanobiomedicine (Rij) 2022; 9:18495435221088374. [PMID: 35677573 PMCID: PMC9168868 DOI: 10.1177/18495435221088374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 02/06/2022] [Indexed: 11/28/2022] Open
Abstract
The aim of this study was to evaluate the cytotoxicity and immune-stimulatory
effect of Mesoporous silica nanoparticle (MSN) Nano-adjuvant on pro-inflammatory
cytokines and pattern recognition receptors (PRR) genes expression in
Caco-2/PBMC co-culture model. MSNs were synthesized and characterized by
scanning electron microscope (SEM), Brunauer Emmett Teller (BET) and Barrett
Joyner Halenda (BJH) techniques. The BET specific surface area of MSNs was
around 947 m2/g and the total pore volume and average pore diameter
were 1.5 cm3/g and 8.01 nm, respectively. At the concentration of
10 µg/mL, MSN showed a low and time-dependent cytotoxicity on Caco-2 cells,
while no cytotoxic effect was observed for 0.1 and 1 µg/mL concentrations after
24, 48 and 72 h. The expression of pro-inflammatory cytokines genes (IL-1, IL-8
and TNF-α) in co-cultures treated with different concentrations of MSN showed a
dose-dependent significant increase up to 17.44, 2.722 and 4.34 folds,
respectively, while the expression augmentation of IL-1 gene was significantly
higher than the others. This indicates slight stimulation of intestinal
inflammation. Different concentrations of MSN significantly increased TLR4 and
NOD2 expression to 4.14 and 2.14 folds, respectively. NOD1 was not affected
significantly. It can be concluded that MSN might increase protective immune
responses against antigens as a vaccine adjuvant candidate. It seems that
stimulation of TNF-α, IL-1, and IL-8 expression in enterocytes probably
transpires through the agonistic activity of MSN for TLRs including TLR4, while
NOD2-associated signaling pathways are also involved. This study provides an
overall picture of MSN as a novel and potent oral adjuvant for mucosal
immunity.
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Affiliation(s)
- Maryam Ghasemi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Bita Bakhshi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Reza Khashei
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Soudi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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17
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Dewi G, Kollanoor Johny A. Lactobacillus in Food Animal Production—A Forerunner for Clean Label Prospects in Animal-Derived Products. FRONTIERS IN SUSTAINABLE FOOD SYSTEMS 2022. [DOI: 10.3389/fsufs.2022.831195] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Lactobacillus, the largest genus within the lactic acid bacteria group, has served diverse roles in improving the quality of foods for centuries. The heterogeneity within this genus has resulted in the industry's continued use of their well-known functions and exploration of novel applications. Moreover, the perceived health benefits in many applications have also made them fond favorites of consumers and researchers alike. Their familiarity lends to their utility in the growing “clean label” movement, of which consumers prefer fewer additions to the food label and opt for recognizable and naturally-derived substances. Our review primarily focuses on the historical use of lactobacilli for their antimicrobial functionality in improving preharvest safety, a critical step to validate their role as biocontrol agents and antibiotic alternatives in food animal production. We also explore their potential as candidates catering to the consumer-driven demand for more authentic, transparent, and socially responsible labeling of animal products.
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18
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Dempsey E, Corr SC. Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives. Front Immunol 2022; 13:840245. [PMID: 35464397 PMCID: PMC9019120 DOI: 10.3389/fimmu.2022.840245] [Citation(s) in RCA: 196] [Impact Index Per Article: 65.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 03/15/2022] [Indexed: 11/13/2022] Open
Abstract
In recent decades, probiotic bacteria have become increasingly popular as a result of mounting scientific evidence to indicate their beneficial role in modulating human health. Although there is strong evidence associating various Lactobacillus probiotics to various health benefits, further research is needed, in particular to determine the various mechanisms by which probiotics may exert these effects and indeed to gauge inter-individual value one can expect from consuming these products. One must take into consideration the differences in individual and combination strains, and conditions which create difficulty in making direct comparisons. The aim of this paper is to review the current understanding of the means by which Lactobacillus species stand to benefit our gastrointestinal health.
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Affiliation(s)
- Elaine Dempsey
- Trinity Biomedical Science Institute, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.,Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Ireland
| | - Sinéad C Corr
- Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, Dublin, Ireland.,APC Microbiome Ireland, University College Cork, Cork, Ireland
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19
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Płaczkiewicz J, Adamczyk-Popławska M, Kozłowska E, Kwiatek A. Both Neisseria gonorrhoeae and Neisseria sicca Induce Cytokine Secretion by Infected Human Cells, but Only Neisseria gonorrhoeae Upregulates the Expression of Long Non-Coding RNAs. Pathogens 2022; 11:pathogens11040394. [PMID: 35456069 PMCID: PMC9031631 DOI: 10.3390/pathogens11040394] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 03/19/2022] [Accepted: 03/21/2022] [Indexed: 12/04/2022] Open
Abstract
Bacteria of the Neisseria genus are Gram-negative diplococci including both pathogenic and commensal species. We focused on pathogenic Neisseria gonorrhoeae and commensal Neisseria sicca. We have demonstrated that not only N. gonorrhoeae, but also N. sicca induce the secretion of pro-inflammatory cytokines IL-6, TNF-α, and chemokines CXCL8 and CCL20 by infected epithelial cells. However, N. sicca triggers a lesser effect than does N. gonorrhoeae. Furthermore, N. gonorrhoeae and N. sicca invoke distinct effects on the expression of genes (JUNB, FOSB, NFKB1, NFKBIA) encoding protein components of AP-1 and NF-κB transcription factors. We have also shown that the infection of epithelial cells by N. gonorrhoeae leads to significant overexpression of the long non-coding RNAs (lncRNAs), including MALAT1, ERICD, and RP11-510N19.5. This effect was not identified for N. sicca. In conclusion, data on the expression of lncRNAs and cytokine secretion in response to Neisseria spp. exposure indicate new directions for research on Neisseria-host interactions and can provide further insights into virulence of not only pathogenic, but also commensal Neisseria spp.
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Affiliation(s)
- Jagoda Płaczkiewicz
- Department of Molecular Virology, Institute of Microbiology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland; (J.P.); (M.A.-P.)
- International Centre for Translational Eye Research, Institute of Physical Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland
| | - Monika Adamczyk-Popławska
- Department of Molecular Virology, Institute of Microbiology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland; (J.P.); (M.A.-P.)
| | - Ewa Kozłowska
- Department of Immunology, Institute of Functional Biology and Ecology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland;
| | - Agnieszka Kwiatek
- Department of Molecular Virology, Institute of Microbiology, Faculty of Biology, University of Warsaw, 02-096 Warsaw, Poland; (J.P.); (M.A.-P.)
- Correspondence:
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20
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Schott T, Reisinger N, Teichmann K, König J, Ladinig A, Mayer E. Establishment of an In Vitro Co-Culture Model of the Piglet Gut to Study Inflammatory Response and Barrier Integrity. PLANTA MEDICA 2022; 88:262-273. [PMID: 34144625 DOI: 10.1055/a-1510-5802] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
In intensive farming, piglets are exposed to various challenges that activate intestinal inflammatory processes, negatively affecting animal health and leading to economic losses. To study the role of the inflammatory response on epithelial barrier integrity, co-culture systems that mimic in vivo complexity are more and more preferred over cell monocultures. In this study, an in vitro gut co-culture model consisting of intestinal porcine epithelial cells and porcine peripheral blood mononuclear cells was established. The model provides an appropriate tool to study the role of the inflammatory response on epithelial barrier integrity and to screen for feed and food components, exerting beneficial effects on gut health. In the established model, inflammation-like reactions and damage of the epithelial barrier, indicated by a decrease of transepithelial electrical resistance, were elicited by activation of peripheral blood mononuclear cells via one of 3 stimuli: lipopolysaccharide, lipoteichoic acid, or concanavalin A. Two phytogenic substances that are commonly used as feed additives, licorice extract and oregano oil, have been shown to counteract the drop in transepithelial electrical resistance values in the gut co-culture model. The established co-culture model provides a powerful in vitro tool to study the role of intestinal inflammation on epithelial barrier integrity. As it consists of porcine epithelial and porcine blood cells it perfectly mimics in vivo conditions and imitates the inter-organ communication of the piglet gut. The developed model is useful to screen for nutritional components or drugs, having the potential to balance intestinal inflammation and strengthen the epithelial barrier integrity in piglets.
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Affiliation(s)
| | | | | | - Jürgen König
- Department of Nutritional Science, University of Vienna, Vienna, Austria
| | - Andrea Ladinig
- Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, Vienna, Austria
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21
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Rath E, Haller D. Intestinal epithelial cell metabolism at the interface of microbial dysbiosis and tissue injury. Mucosal Immunol 2022; 15:595-604. [PMID: 35534699 PMCID: PMC9259489 DOI: 10.1038/s41385-022-00514-x] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 03/16/2022] [Accepted: 04/05/2022] [Indexed: 02/07/2023]
Abstract
The intestinal epithelium represents the most regenerative tissue in the human body, located in proximity to the dense and functionally diverse microbial milieu of the microbiome. Episodes of tissue injury and incomplete healing of the intestinal epithelium are a prerequisite for immune reactivation and account for recurrent, chronically progressing phenotypes of inflammatory bowel diseases (IBD). Mitochondrial dysfunction and associated changes in intestinal epithelial functions are emerging concepts in the pathogenesis of IBD, suggesting impaired metabolic flexibility of epithelial cells affects the regenerative capacity of the intestinal tissue. Next to rendering the intestinal mucosa susceptible to inflammatory triggers, metabolic reprogramming of the epithelium is implicated in shaping adverse microbial environments. In this review, we introduce the concept of "metabolic injury" as a cell autonomous mechanism of tissue wounding in response to mitochondrial perturbation. Furthermore, we highlight epithelial metabolism as intersection of microbiome, immune cells and epithelial regeneration.
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Affiliation(s)
- Eva Rath
- grid.6936.a0000000123222966Technical University of Munich, Chair of Nutrition and Immunology, Freising-Weihenstephan, Germany
| | - Dirk Haller
- grid.6936.a0000000123222966Technical University of Munich, Chair of Nutrition and Immunology, Freising-Weihenstephan, Germany ,grid.6936.a0000000123222966Technical University of Munich, ZIEL Institute for Food & Health, Freising-Weihenstephan, Germany
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Rahman S, Ghiboub M, Donkers JM, van de Steeg E, van Tol EAF, Hakvoort TBM, de Jonge WJ. The Progress of Intestinal Epithelial Models from Cell Lines to Gut-On-Chip. Int J Mol Sci 2021; 22:ijms222413472. [PMID: 34948271 PMCID: PMC8709104 DOI: 10.3390/ijms222413472] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 12/07/2021] [Accepted: 12/13/2021] [Indexed: 12/12/2022] Open
Abstract
Over the past years, several preclinical in vitro and ex vivo models have been developed that helped to understand some of the critical aspects of intestinal functions in health and disease such as inflammatory bowel disease (IBD). However, the translation to the human in vivo situation remains problematic. The main reason for this is that these approaches fail to fully reflect the multifactorial and complex in vivo environment (e.g., including microbiota, nutrition, and immune response) in the gut system. Although conventional models such as cell lines, Ussing chamber, and the everted sac are still used, increasingly more sophisticated intestinal models have been developed over the past years including organoids, InTESTine™ and microfluidic gut-on-chip. In this review, we gathered the most recent insights on the setup, advantages, limitations, and future perspectives of most frequently used in vitro and ex vivo models to study intestinal physiology and functions in health and disease.
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Affiliation(s)
- Shafaque Rahman
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The Netherlands; (S.R.); (M.G.); (T.B.M.H.)
| | - Mohammed Ghiboub
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The Netherlands; (S.R.); (M.G.); (T.B.M.H.)
- Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Emma Children’s Hospital, 1105 AZ Amsterdam, The Netherlands
| | - Joanne M. Donkers
- The Netherlands Organization for Applied Scientific Research (TNO), 3704 HE Zeist, The Netherlands; (J.M.D.); (E.v.d.S.); (E.A.F.v.T.)
| | - Evita van de Steeg
- The Netherlands Organization for Applied Scientific Research (TNO), 3704 HE Zeist, The Netherlands; (J.M.D.); (E.v.d.S.); (E.A.F.v.T.)
| | - Eric A. F. van Tol
- The Netherlands Organization for Applied Scientific Research (TNO), 3704 HE Zeist, The Netherlands; (J.M.D.); (E.v.d.S.); (E.A.F.v.T.)
| | - Theodorus B. M. Hakvoort
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The Netherlands; (S.R.); (M.G.); (T.B.M.H.)
| | - Wouter J. de Jonge
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The Netherlands; (S.R.); (M.G.); (T.B.M.H.)
- Department of Surgery, University of Bonn, 53113 Bonn, Germany
- Correspondence:
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Zhang Y, Mu T, Yang Y, Zhang J, Ren F, Wu Z. Lactobacillus johnsonii Attenuates Citrobacter rodentium-Induced Colitis by Regulating Inflammatory Responses and Endoplasmic Reticulum Stress in Mice. J Nutr 2021; 151:3391-3399. [PMID: 34383918 DOI: 10.1093/jn/nxab250] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 05/14/2021] [Accepted: 07/06/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Probiotics are beneficial in intestinal disorders. However, the benefits of Lactobacillus johnsonii in experimental colitis remain unknown. OBJECTIVES This study aimed to investigate the benefits of L. johnsonii against Citrobacter rodentium-induced colitis. METHODS Thirty-six 5-wk-old female C57BL/6J mice were randomly assigned to 3 groups (n = 12): control (Ctrl) group, Citrobacter rodentium treatment (CR) group (2 × 109 CFU C. rodentium), and Lactobacillus johnsonii and Citrobacter rodentium cotreatment (LJ + CR) group (109 CFU L. johnsonii with C. rodentium). Colon length, mucosal thickness, proinflammatory cytokine genes, and endoplasmic reticulum stress were tested. RESULTS The CR group had greater spleen weight, mucosal thickness, and Ki67+ cells (0.4-4.7 times), and a 23.8% shorter colon length than the Ctrl group, which in the LJ + CR group were 22.4%-77.6% lower and 30% greater than in the CR group, respectively. Relative to the Ctrl group, serum proinflammatory cytokines and immune cell infiltration were greater by 0.3-1.6 times and 6.2-8.8 times in the CR group, respectively; relative to the CR group, these were 19.9%-61.9% and 69.5%-84.2% lower in the LJ + CR group, respectively. The mRNA levels of lysozyme (Lyz) and regenerating islet-derived protein III were 22.7%-36.5% lower and 1.5-2.7 times greater in the CR group than in the Ctrl group, respectively, whereas they were 22.2%-25.7% greater and 57.2%-76.9% lower in the LJ + CR group than in the CR group, respectively. Cell apoptosis was 11.9 times greater in the CR group than in the Ctrl group, and 87.4% lower in the LJ + CR group than in the CR group. Consistently, the protein abundances of C/EBP homologous protein (CHOP), cleaved caspase 1 and 3, activating transcription factor 6α (ATF6A), and phospho-inositol-requiring enzyme 1α (P-IRE1A) were 0.3-2.1 times greater in the CR group and 31.1%-60.4% lower in the LJ + CR group. All these indexes did not differ between the Ctrl and LJ + CR groups, except for CD8+ T lymphocytes and CD11b+ and F4/80+ macrophages (1-1.5 times greater in LJ + CR) and mRNA concentration of Lyz2 (20.1% lower in LJ + CR). CONCLUSIONS L. johnsonii supplementation is a promising nutritional strategy for preventing C. rodentium-induced colitis in mice.
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Affiliation(s)
- Yunchang Zhang
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Tianqi Mu
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Ying Yang
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Jinhua Zhang
- College of Life Science and Bioengineering, Beijing Jiaotong University, Beijing, China
| | - Fazheng Ren
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China
| | - Zhenlong Wu
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, China Agricultural University, Beijing, China
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China
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24
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Rahardja F, Prasetyo D, Shahib MN, Tjahjani S. The Influence of Lactobacillus Acidophilus on MUC1, GAL-3, IL-1β and IL-17 Gene Expression in BALB/c Mice Stomach. Open Microbiol J 2021. [DOI: 10.2174/1874285802115010067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background and Objective:
Lactobacillus acidophilus has been widely used for the management of gastrointestinal carcinoma owing to its immunomodulation effect; however, the role of L. acidophilus and its specific mechanism of action in the stomach is not fully comprehended. The present study evaluated the expression profile of MUC-1, GAL-3, IL -1β, and IL-17 in the L. acidophilus treated mice stomach.
Methods:
The study was conducted utilizing three groups of mice, 6 mice for each group, administered with different doses of L. acidophilus and a control group treated with normal saline. The results were analyzed with the Mann-Whitney Test.
Results:
The results demonstrated that L. acidophilus elevated IL-1β insignificantly and inhibited the expression of IL-17. The MUC-1 expression is influenced by L. acidophilus and inversely proportional to GAL-3 expression.
Conclusion:
Lactobacillus acidophilus plays a prominent role against inflammatory responses and has a potential in the treatment of gastrointestinal cancer.
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25
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The Salivary Microbiota, Cytokines, and Metabolome in Patients with Ankylosing Spondylitis Are Altered and More Proinflammatory than Those in Healthy Controls. mSystems 2021; 6:e0117320. [PMID: 34156295 PMCID: PMC8269253 DOI: 10.1128/msystems.01173-20] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The pathogenesis of ankylosing spondylitis (AS) remains unclear but appears to be associated with heredity and the environment. The mouth links the external environment to the gut and lungs. In the present study, compared to that observed in healthy controls (HCs), AS saliva was depleted of Bacilli such as Streptococcus, enriched with Clostridia such as Veillonellaceae, and enriched with opportunistic pathogens from Proteobacteria such as Brucella spp. and Campylobacter concisus. AS saliva was enriched with 16 cytokines related to inflammation, such as soluble IL-6 receptor α (sIL-6Rα), interleukin 2 (IL-2), IL-10, IL-11, IL-12p40, IL-12p70, IL-20, IL-26, IL-27, IL-28A, IL-29, alpha 2 interferon (IFN-α2), IFN-β, and matrix metalloproteinase 3 (MMP-3). AS saliva was also enriched with hazardous compounds, such as cadaverine and putrescine. AS-altered salivary bacteria, compounds, and cytokines are closely linked with disease indicators. Oral cleaning reduced the levels of proinflammatory cytokines and hazardous compounds in AS saliva compared with HC saliva. AS saliva induced the production of more proinflammatory cytokines, such as IL-12p70 and IL-8, by THP-1 monocyte-derived macrophages, than did HC saliva. The results highlight the importance of salivary microbes, cytokines, and compounds in the development and treatment of AS and provide new ideas for the pathogenesis and treatment of AS. IMPORTANCE Ankylosing spondylitis (AS) affects as much as 0.32% of the population in some districts and causes work disability in one-third of these patients. Microbes are considered to play important roles in AS pathogenesis, and the mouth links the environment to the lungs and the gut. Our results showed that opportunistic pathogens such as Brucella and Campylobacter are enriched in the saliva of AS patients with ankylosing spondylitis. In addition, proinflammatory cytokines and hazardous materials such as putrescine were also enriched in the saliva of AS patients.[AQ1 sentence edit] Interestingly, the opportunistic pathogens and hazardous materials detected in the saliva of AS patients were associated with disease indexes. The saliva of AS patients was shown to induce immune cells to secrete proinflammatory cytokines in vitro. Reducing the levels of salivary microbes can significantly reduce the hazardous materials present in the saliva of AS patients. Our results provide a new perspective on the potential role of salivary microbes, cytokines, and hazardous compounds in the pathogenesis and treatment of AS.
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Simon E, Călinoiu LF, Mitrea L, Vodnar DC. Probiotics, Prebiotics, and Synbiotics: Implications and Beneficial Effects against Irritable Bowel Syndrome. Nutrients 2021; 13:nu13062112. [PMID: 34203002 PMCID: PMC8233736 DOI: 10.3390/nu13062112] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 06/05/2021] [Accepted: 06/16/2021] [Indexed: 12/12/2022] Open
Abstract
Irritable bowel syndrome (IBS) is still a common functional gastrointestinal disease that presents chronic abdominal symptoms but with a pathophysiology that is not yet fully elucidated. Moreover, the use of the synergistic combination of prebiotics and probiotics, known as synbiotics, for IBS therapy is still in the early stages. Advancements in technology led to determining the important role played by probiotics in IBS, whereas the present paper focuses on the detailed review of the various pathophysiologic mechanisms of action of probiotics, prebiotics, and synbiotics via multidisciplinary domains involving the gastroenterology (microbiota modulation, alteration of gut barrier function, visceral hypersensitivity, and gastrointestinal dysmotility) immunology (intestinal immunological modulation), and neurology (microbiota–gut–brain axis communication and co-morbidities) in mitigating the symptoms of IBS. In addition, this review synthesizes literature about the mechanisms involved in the beneficial effects of prebiotics and synbiotics for patients with IBS, discussing clinical studies testing the efficiency and outcomes of synbiotics used as therapy for IBS.
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Affiliation(s)
- Elemer Simon
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania; (E.S.); (L.F.C.)
| | - Lavinia Florina Călinoiu
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania; (E.S.); (L.F.C.)
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania;
| | - Laura Mitrea
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania;
| | - Dan Cristian Vodnar
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania; (E.S.); (L.F.C.)
- Institute of Life Sciences, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3–5, 400372 Cluj-Napoca, Romania;
- Correspondence: ; Tel.: +40-747-341-881
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Haller D. Intestinal microbiota in health and disease - Seeding multidisciplinary research in Germany. Int J Med Microbiol 2021; 311:151514. [PMID: 34111652 DOI: 10.1016/j.ijmm.2021.151514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 06/02/2021] [Indexed: 11/30/2022] Open
Affiliation(s)
- Dirk Haller
- Chair of Nutrition and Immunology, Technical University of Munich, Germany
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Ghasemi M, Bakhshi B, Khashei R, Soudi S, Boustanshenas M. Vibrio cholerae toxin coregulated pilus provokes inflammatory responses in Coculture model of Caco-2 and peripheral blood mononuclear cells (PBMC) leading to increased colonization. Microbiol Immunol 2021; 65:238-244. [PMID: 33913531 DOI: 10.1111/1348-0421.12889] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 03/09/2021] [Accepted: 04/26/2021] [Indexed: 11/30/2022]
Abstract
The aim of this study was to assess the modulatory effect of TcpA in the expression of CEACAM1 adhesin molecule and IL-1, IL-8, and TNF-α pro-inflammatory cytokines in the Coculture model of Caco-2/PBMC (peripheral blood mononuclear cell) that can mimic the intestinal milieu. The TcpA gene from Vibrio cholerae ATCC14035 was cloned in pET-28a and transformed into Escherichia coli Bl-21. The recombinant TcpA-His6 protein was expressed and purified using Ni-column chromatography. The sequencing of transformed plasmid and Western blot analysis of purified protein confirmed the identity of rTcp. The cytotoxicity of different concentrations of recombinant protein for human colon carcinoma cell line (human colorectal adenocarcinoma cell [Caco-2 cell]) was assessed by MTT assay and showed viability of 92%, 82%, and 70%, for 10 µg/mL of TcpA after 24, 48, and 72 h, respectively. Co-cultures of Caco-2 and PBMCs were used to mimic the intestinal milieu and treated with different concentrations of rTcpA (1, 5, 10, and 50 µg/mL). Our data showed about 2.04-, 3.37-, 3.68-, and 42.7-fold increase in CEACAM1 gene expression, respectively, compared with the nontreated Caco-2/PBMC Coculture. Moreover, the expression of IL-1, IL-8, and TNF-α genes was significantly increased up to 15.75-, 7.04-, and 80.95-folds, respectively. In conclusion, V. cholerae TcpA induces statistically significant dose-dependent stimulatory effect on TNF-α, IL-,1, and IL-8 pro-inflammatory cytokines expression. Of these, TNF-α was much more affected which, consequently, elevated the CEACAM1 expression level in IECs. This suggests that TcpA protein is a critical effector as an inducer of increased adhesion potential of V. cholera as well as inflammatory responses of host intestinal tissue.
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Affiliation(s)
- Maryam Ghasemi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Bita Bakhshi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Reza Khashei
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Soudi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mina Boustanshenas
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
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Raheem A, Liang L, Zhang G, Cui S. Modulatory Effects of Probiotics During Pathogenic Infections With Emphasis on Immune Regulation. Front Immunol 2021; 12:616713. [PMID: 33897683 PMCID: PMC8060567 DOI: 10.3389/fimmu.2021.616713] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 02/12/2021] [Indexed: 12/11/2022] Open
Abstract
In order to inhibit pathogenic complications and to enhance animal and poultry growth, antibiotics have been extensively used for many years. Antibiotics applications not only affect target pathogens but also intestinal beneficially microbes, inducing long-lasting changes in intestinal microbiota associated with diseases. The application of antibiotics also has many other side effects like, intestinal barrier dysfunction, antibiotics residues in foodstuffs, nephropathy, allergy, bone marrow toxicity, mutagenicity, reproductive disorders, hepatotoxicity carcinogenicity, and antibiotic-resistant bacteria, which greatly compromise the efficacy of antibiotics. Thus, the development of new antibiotics is necessary, while the search for antibiotic alternatives continues. Probiotics are considered the ideal antibiotic substitute; in recent years, probiotic research concerning their application during pathogenic infections in humans, aquaculture, poultry, and livestock industry, with emphasis on modulating the immune system of the host, has been attracting considerable interest. Hence, the adverse effects of antibiotics and remedial effects of probiotics during infectious diseases have become central points of focus among researchers. Probiotics are live microorganisms, and when given in adequate quantities, confer good health effects to the host through different mechanisms. Among them, the regulation of host immune response during pathogenic infections is one of the most important mechanisms. A number of studies have investigated different aspects of probiotics. In this review, we mainly summarize recent discoveries and discuss two important aspects: (1) the application of probiotics during pathogenic infections; and (2) their modulatory effects on the immune response of the host during infectious and non-infectious diseases.
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Affiliation(s)
- Abdul Raheem
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Lin Liang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Guangzhi Zhang
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
| | - Shangjin Cui
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China
- Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, China
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Sukhotnik I, Ben-Shahar Y, Pollak Y, Cohen S, Moran-Lev H, Koppelmann T, Gorenberg M. Intestinal dysmotility after bowel resection in rats is associated with decreased ghrelin and vimentin expression and loss of intestinal cells of Cajal. Am J Physiol Gastrointest Liver Physiol 2021; 320:G283-G294. [PMID: 33325807 PMCID: PMC8609566 DOI: 10.1152/ajpgi.00223.2020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
This study provides novel insight into the mechanisms of intestinal dysmotility following massive small bowel resection. We show that 2 wk after bowel resection in rats, impaired intestinal motility was associated with loss of interstitial cells of Cajal (ICC; downregulation of transmembrane member 16A (TMEM16A) and c-kit expression) as well as with decreased vimentin, desmin, and ghrelin levels. Impaired intestinal motility led to a decrease in final body weight, suggesting less effective nutrient absorption. The purpose of this study was to evaluate the mechanisms of intestinal motility in a rat model of short bowel syndrome (SBS). Rats were divided into three groups: Sham rats underwent bowel transection; SBS-NSI rats underwent a 75% bowel resection and presented with normal intestinal size (NSI) at euthanasia and hypermotility patterns; SBS-DYS showed dysmotile (DYS) enlarged intestine and inhibited motility patterns. Animals were euthanized after 2 wk. Illumina's digital gene expression (DGE) analysis was used to determine the intestinal motility-related gene expression profiling in mucosal samples. Intestinal motility-related and ICC genes and protein expression in intestinal muscle layer were determined using real-time PCR, Western blotting, and immunohistochemistry. Gastrointestinal tract motility was studied by microcomputer tomography. From 10 Ca2+ signaling pathway-related genes, six genes in jejunum and seven genes in ileum were downregulated in SBS vs. Sham animals. Downregulation of TMEM16A mRNA and protein was confirmed by real-time PCR. Rapid intestinal transit time in SBS-NSI rats correlated with a mild decrease in TMEM16A, c-kit, and vimentin mRNA and protein expression (vs/. Sham animals). SBS-DYS rats demonstrated enlarged intestinal loops and delayed small intestinal emptying (on imaging studies) that were correlated with marked downregulation in TMEM16A, c-kit, vimentin, and ghrelin mRNA and protein levels compared with the other two groups. In conclusion, 2 wk following massive bowel resection in rats, impaired intestinal motility was associated with decreased vimentin and ghrelin gene and protein levels as well as loss of ICC (c-kit and TMEM16A).NEW & NOTEWORTHY This study provides novel insight into the mechanisms of intestinal dysmotility following massive small bowel resection. We show that 2 weeks after bowel resection in rats, impaired intestinal motility was associated with loss of interstitial cells of Cajal (downregulation of TMEM 16A, and c-kit expression) as well as with decreased vimentin, desmin, and ghrelin levels. Impaired intestinal motility led to decrease in final body weight, suggesting less effective nutrient absorption.
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Affiliation(s)
- Igor Sukhotnik
- 1Laboratory of Intestinal Adaptation and Recovery, Department of Pediatric Surgery, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel,3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yoav Ben-Shahar
- 1Laboratory of Intestinal Adaptation and Recovery, Department of Pediatric Surgery, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel,4The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Yulia Pollak
- 1Laboratory of Intestinal Adaptation and Recovery, Department of Pediatric Surgery, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Shlomi Cohen
- 2Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel,3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Hadar Moran-Lev
- 2Pediatric Gastroenterology Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel,3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tal Koppelmann
- 1Laboratory of Intestinal Adaptation and Recovery, Department of Pediatric Surgery, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Migel Gorenberg
- 4The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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31
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Delgado-Venegas CS, Martínez-Hernández SL, Cervantes-García D, Montes de Oca-Luna R, de Jesús Loera-Arias M, Mata-Martínez MG, Ventura-Juárez J, Muñoz-Ortega MH. Modulating effects of the probiotic Lactococcus lactis on the hepatic fibrotic process induced by CCl 4 in Wistar rats. Exp Ther Med 2021; 21:339. [PMID: 33732312 PMCID: PMC7903445 DOI: 10.3892/etm.2021.9770] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 12/04/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatic cirrhosis is a chronic disease that affects one fifth of the World's population and is the third leading cause of death in Mexico. Attempts have been made to develop treatments for this hepatic cirrhosis, which include manipulating the intestinal microbiota and thus decreasing the early inflammatory response. The microbiota is reportedly altered in patients with cirrhosis. Due to its immunomodulatory properties and its ability to survive in the gastrointestinal tract, Lactococcus lactis (L. lactis) has been used as a therapeutic measure in inflammatory disorders of the colon. The objective of the present study was to evaluate the efficacy of the L. lactis probiotic NZ9000 in preventing tetrachloromethane (CCl4)-induced experimental hepatic fibrosis. The following 4 groups were included in the experimental stage (n=5): i) Control group; ii) L. lactis group; iii) CCl4 group; and iv) L. lactis-CCl4 group. For the first 2 weeks, L. lactis was orally administered to the L. lactis and L. lactis-CCl4 groups; CCl4 was then peritoneally administered to the lactis-CCl4 group for a further 4 weeks (in addition to the probiotic), while the L. lactis group received the probiotic only. For the CCl4 group, CCl4 was administered for 4 weeks. The experimental groups were all compared with the control group and the L. lactis + CCl4 group. Tissue samples were analyzed histologically and biochemically, and the gene expression levels of interleukin (IL)-1, IL-10 and forkhead box protein P3 (FoxP3) were determined. L. lactis decreased hepatic cirrhosis by preventing steatosis and fibrosis, and by reducing the levels of AST and ALT. Subchronic CCl4 injury induced upregulation of the IL-1β gene in the liver, which was decreased by L. lactis. It was also found that the group treated with L. lactis showed increased expression of Foxp3 in the liver and IL-10 in the gut. These results suggested that oral administration of L. lactis may be a potential probiotic to prevent or protect against CCl4-induced liver injury.
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Affiliation(s)
| | - Sandra Luz Martínez-Hernández
- Center for Basic Sciences, Department of Morphology, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico
| | - Daniel Cervantes-García
- National Council of Science and Technology, Center for Basic Sciences, Department of Microbiology, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico
| | - Roberto Montes de Oca-Luna
- Faculty of Medicine, Department of Histology, Autonomous University of Nuevo Léon, Monterrey, Nuevo León, 64460, Mexico
| | - María de Jesús Loera-Arias
- Faculty of Medicine, Department of Histology, Autonomous University of Nuevo Léon, Monterrey, Nuevo León, 64460, Mexico
| | - María Guadalupe Mata-Martínez
- Center for Basic Sciences, Department of Morphology, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico
| | - Javier Ventura-Juárez
- Center for Basic Sciences, Department of Morphology, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico
| | - Martín Humberto Muñoz-Ortega
- Center of Basic Sciences, Department of Chemistry, Autonomous University of Aguascalientes, Aguascalientes 20131, Mexico
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Inflammatory Responses of Porcine MoDC and Intestinal Epithelial Cells in a Direct-Contact Co-culture System Following a Bacterial Challenge. Inflammation 2021; 43:552-567. [PMID: 31811548 DOI: 10.1007/s10753-019-01137-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Intestinal epithelial cells (IEC) and immune cells, such as dendritic cells (DC), jointly control the immune response towards luminal pathogens in the intestinal mucosa. Crosstalk between IEC and DC is crucial for coordinating immune responses and occurs via soluble factors and direct cell-cell contacts. The present study aimed at establishing a direct-contact co-culture model of porcine IEC and DC to mimic these interactions. The effects of (1) co-cultivation of the two cell types and (2) bacterial infection on the inflammatory response patterns of each of the cell types were determined with a special focus on the canonical and non-canonical inflammasome signaling pathways. In infection experiments, in vitro cultures were exposed to either the probiotic Enterococcus (E.) faecium NCIMB 10415 or enterotoxigenic Escherichia coli (ETEC). In porcine IEC (IPEC-J2), co-cultivation with porcine monocyte-derived DC (MoDC) resulted in reduced basal NLRP3 (nucleotide oligomerization domain [NOD]-like receptor [NLR] family, pyrin domain containing 3) inflammasome mRNA levels in unstimulated conditions. In porcine MoDC, the presence of IPEC-J2 cells evoked a noticeable decrease of interleukin (IL)-8 and transforming growth factor-β (TGF-β) mRNA and protein expression. ETEC, in contrast to E. faecium, modulated the inflammasome pathway in IPEC-J2 cells and porcine MoDC. Co-cultured IPEC-J2 cells showed an augmented inflammasome response to ETEC infection. By contrast, MoDC revealed a weakened ETEC response under such co-culture conditions as indicated by a reduction of inflammasome-related IL-1β protein release. Our data indicate that the close contact between IEC and resident immune cells has a major effect on their immunological behavior.
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Zhang J, Wan J, Chen D, Yu B, He J. Low-Molecular-Weight Chitosan Attenuates Lipopolysaccharide-Induced Inflammation in IPEC-J2 Cells by Inhibiting the Nuclear Factor-κB Signalling Pathway. Molecules 2021; 26:molecules26030569. [PMID: 33499133 PMCID: PMC7865926 DOI: 10.3390/molecules26030569] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 01/12/2021] [Accepted: 01/16/2021] [Indexed: 02/07/2023] Open
Abstract
Low-molecular-weight chitosan (LMWC), a product of chitosan deacetylation, possesses anti-inflammatory effects. In the present study, a porcine small intestinal epithelial cell line, IPEC-J2, was used to assess the protective effects of LMWC on lipopolysaccharide (LPS)-induced intestinal epithelial cell injury. IPEC-J2 cells were pretreated with or without LMWC (400 μg/mL) in the presence or absence of LPS (5 μg/mL) for 6 h. LMWC pretreatment increased (p < 0.05) the occludin abundance and decreased (p < 0.05) the tumour necrosis factor-α (TNF-α) production, apoptosis rate and cleaved cysteinyl aspartate-specific protease-3 (caspase-3) and -8 contents in LPS-treated IPEC-J2 cells. Moreover, LMWC pretreatment downregulated (p < 0.05) the expression levels of TNF receptor 1 (TNFR1) and TNFR-associated death domain and decreased (p < 0.05) the nuclear and cytoplasmic abundance of nuclear factor-κB (NF-κB) p65 in LPS-stimulated IPEC-J2 cells. These results suggest that LMWC exerts a mitigation effect on LPS-induced intestinal epithelial cell damage by suppressing TNFR1-mediated apoptosis and decreasing the production of proinflammatory cytokines via the inhibition of NF-κB signalling pathway.
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Affiliation(s)
| | | | | | | | - Jun He
- Correspondence: ; Tel.: +86-13419354223; Fax: +86-28-86291781
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Yao J, Wang L, Zhang W, Liu M, Niu J. Effects of Bacillus megaterium on growth performance, serum biochemical parameters, antioxidant capacity, and immune function in suckling calves. Open Life Sci 2020; 15:1033-1041. [PMID: 33817289 PMCID: PMC7874550 DOI: 10.1515/biol-2020-0106] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 09/27/2020] [Accepted: 10/04/2020] [Indexed: 11/15/2022] Open
Abstract
Background This study was conducted to investigate the effects of Bacillus megaterium on growth performance, serum biochemical parameters, antioxidant capacity, and immune function in suckling calves. Methods In total, 20 1-day-old Holstein calves with similar body weight (BW) and good health condition were randomly assigned into two groups with ten replicates per group and one calf per replicate. The control group (CON group) was fed a basal diet, whereas the B. megaterium group (BM group) was fed the basal diet supplemented with 500 mg/day/head of B. megaterium (1010 CFU/g) for 28 days. Results The results revealed that the BM group showed an increase in final BW, daily weight gain, and feed-to-gain ratio (p < 0.05) and a decrease in diarrhea rate. Moreover, the concentrations of serum cholesterol and high-density lipoprotein decreased (p < 0.05) in the BM group compared with the CON group at 28 days. The level of serum glutathione was higher (p < 0.05) in the BM group than that of the CON group at 14 days, whereas the level of serum malondialdehyde decreased (p < 0.01) in the BM group compared with the CON group at 28 days. In addition, compared with the CON group (p < 0.05), the concentrations of serum IgA, IgM, IgG, and IL-4 were higher, whereas the concentration of serum TNF-α decreased in the BM group at 28 days. Conclusion B. megaterium had beneficial effects on the improvement of growth performance, immune function, and intestinal oxidative status of suckling calves.
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Affiliation(s)
- Jun Yao
- College of Animal Science & Technology, Shihezi University, Shihezi 832003, China
| | - Lili Wang
- School of Bioengineering, Dalian University of Technology, Dalian 116000, China
| | - Wenju Zhang
- College of Animal Science & Technology, Shihezi University, Shihezi 832003, China
| | - Mengjian Liu
- College of Animal Science & Technology, Shihezi University, Shihezi 832003, China
| | - Junli Niu
- College of Animal Science & Technology, Shihezi University, Shihezi 832003, China
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Weindl G. Immunocompetent Human Intestinal Models in Preclinical Drug Development. Handb Exp Pharmacol 2020; 265:219-233. [PMID: 33349897 DOI: 10.1007/164_2020_429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2023]
Abstract
The intestinal epithelial barrier, together with the microbiome and local immune system, is a critical component that maintains intestinal homeostasis. Dysfunction may lead to chronic inflammation, as observed in inflammatory bowel diseases. Animal models have historically been used in preclinical research to identify and validate new drug targets in intestinal inflammatory diseases. Yet, limitations about their biological relevance to humans and advances in tissue engineering have forced the development of more complex three-dimensional reconstructed intestinal epithelium. By introducing immune and commensal microbial cells, these models more accurately mimic the gut's physiology and the pathophysiological changes occurring in vivo in the inflamed intestine. Specific advantages and limitations of two-dimensional (2D) and three-dimensional (3D) intestinal models such as coculture systems, organoids, and microfluidic devices to study inflammatory and immune-related responses are highlighted. While current cell culture models lack the cellular and molecular complexity observed in vivo, the emphasis is put on how these models can be used to improve preclinical drug development for inflammatory diseases of the intestine.
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Affiliation(s)
- Günther Weindl
- Pharmacology and Toxicology Section, Pharmaceutical Institute, University of Bonn, Bonn, Germany.
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36
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Ali A, Tan H, Kaiko GE. Role of the Intestinal Epithelium and Its Interaction With the Microbiota in Food Allergy. Front Immunol 2020; 11:604054. [PMID: 33365031 PMCID: PMC7750388 DOI: 10.3389/fimmu.2020.604054] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 11/10/2020] [Indexed: 12/12/2022] Open
Abstract
The intestinal epithelial tract forms a dynamic lining of the digestive system consisting of a range of epithelial cell sub-types with diverse functions fulfilling specific niches. The intestinal epithelium is more than just a physical barrier regulating nutrient uptake, rather it plays a critical role in homeostasis through its intrinsic innate immune function, pivotal regulation of antigen sensitization, and a bi-directional interplay with the microbiota that evolves with age. In this review we will discuss these functions of the epithelium in the context of food allergy.
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Affiliation(s)
- Ayesha Ali
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.,Hunter Medical Research Institute, Newcastle, NSW, Australia
| | - HuiYing Tan
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.,Hunter Medical Research Institute, Newcastle, NSW, Australia
| | - Gerard E Kaiko
- School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.,Hunter Medical Research Institute, Newcastle, NSW, Australia
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Ghasemi M, Bakhshi B, Khashei R, Soudi S. Modulatory effect of Vibrio cholerae toxin co-regulated pilus on mucins, toll-like receptors and NOD genes expression in co-culture model of Caco-2 and peripheral blood mononuclear cells (PBMC). Microb Pathog 2020; 149:104566. [DOI: 10.1016/j.micpath.2020.104566] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 10/01/2020] [Accepted: 10/01/2020] [Indexed: 10/23/2022]
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Negretti NM, Ye Y, Malavasi LM, Pokharel SM, Huynh S, Noh S, Klima CL, Gourley CR, Ragle CA, Bose S, Looft T, Parker CT, Clair G, Adkins JN, Konkel ME. A porcine ligated loop model reveals new insight into the host immune response against Campylobacter jejuni. Gut Microbes 2020; 12:1-25. [PMID: 32887530 PMCID: PMC7524355 DOI: 10.1080/19490976.2020.1814121] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 08/12/2020] [Accepted: 08/17/2020] [Indexed: 02/03/2023] Open
Abstract
The symptoms of infectious diarrheal disease are mediated by a combination of a pathogen's virulence factors and the host immune system. Campylobacter jejuni is the leading bacterial cause of diarrhea worldwide due to its near-ubiquitous zoonotic association with poultry. One of the outstanding questions is to what extent the bacteria are responsible for the diarrheal symptoms via intestinal cell necrosis versus immune cell initiated tissue damage. To determine the stepwise process of inflammation that leads to diarrhea, we used a piglet ligated intestinal loop model to study the intestinal response to C. jejuni. Pigs were chosen due to the anatomical similarity between the porcine and the human intestine. We found that the abundance of neutrophil related proteins increased in the intestinal lumen during C. jejuni infection, including proteins related to neutrophil migration (neutrophil elastase and MMP9), actin reorganization (Arp2/3), and antimicrobial proteins (lipocalin-2, myeloperoxidase, S100A8, and S100A9). The appearance of neutrophil proteins also corresponded with increases of the inflammatory cytokines IL-8 and TNF-α. Compared to infection with the C. jejuni wild-type strain, infection with the noninvasive C. jejuni ∆ciaD mutant resulted in a blunted inflammatory response, with less inflammatory cytokines and neutrophil markers. These findings indicate that intestinal inflammation is driven by C. jejuni virulence and that neutrophils are the predominant cell type responding to C. jejuni infection. We propose that this model can be used as a platform to study the early immune events during infection with intestinal pathogens.
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Affiliation(s)
- Nicholas M Negretti
- School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
| | - Yinyin Ye
- Integrative Omics, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Lais M Malavasi
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
| | - Swechha M Pokharel
- Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
| | - Steven Huynh
- Produce Safety and Microbiology, United States Department of Agriculture-Agricultural Research Service, Albany, CA, USA
| | - Susan Noh
- Animal Disease Research Unit, Agricultural Research Service, United States Department of Agriculture, Pullman, WA, USA
- Washington Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
| | - Cassidy L Klima
- Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA, USA
| | - Christopher R Gourley
- School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
| | - Claude A Ragle
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
| | - Santanu Bose
- Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
| | - Torey Looft
- Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA, USA
| | - Craig T Parker
- Produce Safety and Microbiology, United States Department of Agriculture-Agricultural Research Service, Albany, CA, USA
| | - Geremy Clair
- Integrative Omics, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Joshua N Adkins
- Integrative Omics, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Michael E Konkel
- School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
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Oriano M, Zorzetto L, Guagliano G, Bertoglio F, van Uden S, Visai L, Petrini P. The Open Challenge of in vitro Modeling Complex and Multi-Microbial Communities in Three-Dimensional Niches. Front Bioeng Biotechnol 2020; 8:539319. [PMID: 33195112 PMCID: PMC7606986 DOI: 10.3389/fbioe.2020.539319] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 09/28/2020] [Indexed: 12/03/2022] Open
Abstract
The comprehension of the underlying mechanisms of the interactions within microbial communities represents a major challenge to be faced to control their outcome. Joint efforts of in vitro, in vivo and ecological models are crucial to controlling human health, including chronic infections. In a broader perspective, considering that polymicrobial communities are ubiquitous in nature, the understanding of these mechanisms is the groundwork to control and modulate bacterial response to any environmental condition. The reduction of the complex nature of communities of microorganisms to a single bacterial strain could not suffice to recapitulate the in vivo situation observed in mammals. Furthermore, some bacteria can adapt to various physiological or arduous environments embedding themselves in three-dimensional matrices, secluding from the external environment. Considering the increasing awareness that dynamic complex and dynamic population of microorganisms (microbiota), inhabiting different apparatuses, regulate different health states and protect against pathogen infections in a fragile and dynamic equilibrium, we underline the need to produce models to mimic the three-dimensional niches in which bacteria, and microorganisms in general, self-organize within a microbial consortium, strive and compete. This review mainly focuses, as a case study, to lung pathology-related dysbiosis and life-threatening diseases such as cystic fibrosis and bronchiectasis, where the co-presence of different bacteria and the altered 3D-environment, can be considered as worst-cases for chronic polymicrobial infections. We illustrate the state-of-art strategies used to study biofilms and bacterial niches in chronic infections, and multispecies ecological competition. Although far from the rendering of the 3D-environments and the polymicrobial nature of the infections, they represent the starting point to face their complexity. The increase of knowledge respect to the above aspects could positively affect the actual healthcare scenario. Indeed, infections are becoming a serious threat, due to the increasing bacterial resistance and the slow release of novel antibiotics on the market.
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Affiliation(s)
- Martina Oriano
- Molecular Medicine Department (DMM), Center for Health Technologies (CHT), UdR INSTM, University of Pavia, Pavia, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Internal Medicine Department, Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Laura Zorzetto
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany
| | - Giuseppe Guagliano
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta” and UdR INSTM Politecnico di Milano, Milan, Italy
| | - Federico Bertoglio
- Molecular Medicine Department (DMM), Center for Health Technologies (CHT), UdR INSTM, University of Pavia, Pavia, Italy
- Technische Universität Braunschweig, Institute of Biochemistry, Biotechnology and Bioinformatic, Department of Biotechnology, Braunschweig, Germany
| | - Sebastião van Uden
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta” and UdR INSTM Politecnico di Milano, Milan, Italy
| | - Livia Visai
- Molecular Medicine Department (DMM), Center for Health Technologies (CHT), UdR INSTM, University of Pavia, Pavia, Italy
- Department of Occupational Medicine, Toxicology and Environmental Risks, Istituti Clinici Scientifici (ICS) Maugeri, IRCCS, Pavia, Italy
| | - Paola Petrini
- Department of Chemistry, Materials and Chemical Engineering “Giulio Natta” and UdR INSTM Politecnico di Milano, Milan, Italy
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Morsink MAJ, Willemen NGA, Leijten J, Bansal R, Shin SR. Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications. MICROMACHINES 2020; 11:mi11090849. [PMID: 32932680 PMCID: PMC7570325 DOI: 10.3390/mi11090849] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/07/2020] [Accepted: 09/08/2020] [Indexed: 12/27/2022]
Abstract
Understanding the immune system is of great importance for the development of drugs and the design of medical implants. Traditionally, two-dimensional static cultures have been used to investigate the immune system in vitro, while animal models have been used to study the immune system’s function and behavior in vivo. However, these conventional models do not fully emulate the complexity of the human immune system or the human in vivo microenvironment. Consequently, many promising preclinical findings have not been reproduced in human clinical trials. Organ-on-a-chip platforms can provide a solution to bridge this gap by offering human micro-(patho)physiological systems in which the immune system can be studied. This review provides an overview of the existing immune-organs-on-a-chip platforms, with a special emphasis on interorgan communication. In addition, future challenges to develop a comprehensive immune system-on-chip model are discussed.
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Affiliation(s)
- Margaretha A. J. Morsink
- Division of Engineering in Medicine, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Cambridge, MA 02139, USA; (M.A.J.M.); (N.G.A.W.)
- Department of Developmental BioEngineering, Faculty of Science and Technology, Technical Medical Centre, University of Twente, Drienerlolaan 5, 7522 NB Enschede, The Netherlands;
- Translational Liver Research, Department of Medical Cell BioPhysics, Technical Medical Centre, Faculty of Science and Technology, University of Twente Drienerlolaan 5, 7522 NB Enschede, The Netherlands;
| | - Niels G. A. Willemen
- Division of Engineering in Medicine, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Cambridge, MA 02139, USA; (M.A.J.M.); (N.G.A.W.)
- Department of Developmental BioEngineering, Faculty of Science and Technology, Technical Medical Centre, University of Twente, Drienerlolaan 5, 7522 NB Enschede, The Netherlands;
| | - Jeroen Leijten
- Department of Developmental BioEngineering, Faculty of Science and Technology, Technical Medical Centre, University of Twente, Drienerlolaan 5, 7522 NB Enschede, The Netherlands;
| | - Ruchi Bansal
- Translational Liver Research, Department of Medical Cell BioPhysics, Technical Medical Centre, Faculty of Science and Technology, University of Twente Drienerlolaan 5, 7522 NB Enschede, The Netherlands;
| | - Su Ryon Shin
- Division of Engineering in Medicine, Department of Medicine, Harvard Medical School, Brigham and Women’s Hospital, Cambridge, MA 02139, USA; (M.A.J.M.); (N.G.A.W.)
- Correspondence: ; Tel.: +1-617-768-8320
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Wodzanowski KA, Cassel SE, Grimes CL, Kloxin AM. Tools for probing host-bacteria interactions in the gut microenvironment: From molecular to cellular levels. Bioorg Med Chem Lett 2020; 30:127116. [PMID: 32223923 PMCID: PMC7476074 DOI: 10.1016/j.bmcl.2020.127116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/28/2020] [Accepted: 03/15/2020] [Indexed: 12/31/2022]
Abstract
Healthy function of the gut microenvironment is dependent on complex interactions between the bacteria of the microbiome, epithelial and immune (host) cells, and the surrounding tissue. Misregulation of these interactions is implicated in disease. A range of tools have been developed to study these interactions, from mechanistic studies to therapeutic evaluation. In this Digest, we highlight select tools at the cellular and molecular level for probing specific cell-microenvironment interactions. Approaches are overviewed for controlling and probing cell-cell interactions, from transwell and microfluidic devices to engineered bacterial peptidoglycan fragments, and cell-matrix interactions, from three-dimensional scaffolds to chemical handles for in situ modifications.
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Affiliation(s)
| | - Samantha E Cassel
- Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, United States
| | - Catherine L Grimes
- Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, United States; Biological Sciences, University of Delaware, Newark, DE 19716, United States.
| | - April M Kloxin
- Chemical and Biomolecular Engineering, University of Delaware, Newark, DE 19716, United States; Materials Science and Engineering, University of Delaware, Newark, DE 19716, United States.
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Miller CP, Shin W, Ahn EH, Kim HJ, Kim DH. Engineering Microphysiological Immune System Responses on Chips. Trends Biotechnol 2020; 38:857-872. [PMID: 32673588 DOI: 10.1016/j.tibtech.2020.01.003] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 01/06/2020] [Accepted: 01/07/2020] [Indexed: 02/06/2023]
Abstract
Tissues- and organs-on-chips are microphysiological systems (MPSs) that model the architectural and functional complexity of human tissues and organs that is lacking in conventional cell monolayer cultures. While substantial progress has been made in a variety of tissues and organs, chips recapitulating immune responses have not advanced as rapidly. This review discusses recent progress in MPSs for the investigation of immune responses. To illustrate recent developments, we focus on two cases in point: immunocompetent tumor microenvironment-on-a-chip devices that incorporate stromal and immune cell components and pathomimetic modeling of human mucosal immunity and inflammatory crosstalk. More broadly, we discuss the development of systems immunology-on-a-chip devices that integrate microfluidic engineering approaches with high-throughput omics measurements and emerging immunological applications of MPSs.
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Affiliation(s)
- Chris P Miller
- Department of Bioengineering, University of Washington, Seattle, WA 98109, USA
| | - Woojung Shin
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA
| | - Eun Hyun Ahn
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA
| | - Hyun Jung Kim
- Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA; Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA; Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
| | - Deok-Ho Kim
- Department of Bioengineering, University of Washington, Seattle, WA 98109, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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Castan L, Bøgh KL, Maryniak NZ, Epstein MM, Kazemi S, O'Mahony L, Bodinier M, Smit JJ, Bilsen JHM, Blanchard C, Głogowski R, Kozáková H, Schwarzer M, Noti M, Wit N, Bouchaud G, Bastiaan‐Net S. Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins? Allergy 2020; 75:289-301. [PMID: 31187876 PMCID: PMC7065134 DOI: 10.1111/all.13943] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 05/12/2019] [Accepted: 05/31/2019] [Indexed: 02/06/2023]
Abstract
Significant efforts are necessary to introduce new dietary protein sources to feed a growing world population while maintaining food supply chain sustainability. Such a sustainable protein transition includes the use of highly modified proteins from side streams or the introduction of new protein sources that may lead to increased clinically relevant allergic sensitization. With food allergy being a major health problem of increasing concern, understanding the potential allergenicity of new or modified proteins is crucial to ensure public health protection. The best predictive risk assessment methods currently relied on are in vivo models, making the choice of endpoint parameters a key element in evaluating the sensitizing capacity of novel proteins. Here, we provide a comprehensive overview of the most frequently used in vivo and ex vivo endpoints in murine food allergy models, addressing their strengths and limitations for assessing sensitization risks. For optimal laboratory‐to‐laboratory reproducibility and reliable use of predictive tests for protein risk assessment, it is important that researchers maintain and apply the same relevant parameters and procedures. Thus, there is an urgent need for a consensus on key food allergy parameters to be applied in future food allergy research in synergy between both knowledge institutes and clinicians.
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Affiliation(s)
| | - Katrine L. Bøgh
- National Food Institute Technical University of Denmark Kgs. Lyngby Denmark
| | | | - Michelle M. Epstein
- Experimental Allergy Laboratory, Department of Dermatology Medical University of Vienna Vienna Austria
| | - Sahar Kazemi
- Experimental Allergy Laboratory, Department of Dermatology Medical University of Vienna Vienna Austria
| | - Liam O'Mahony
- Department of Medicine, APC Microbiome Ireland National University of Ireland Cork Ireland
- Department of Microbiology, APC Microbiome Ireland National University of Ireland Cork Ireland
| | | | - Joost J. Smit
- Institute for Risk Assessment Sciences Utrecht University Utrecht The Netherlands
| | | | | | - Robert Głogowski
- Department of Animal Breeding and Production Warsaw University of Life Sciences Warsaw Poland
| | - Hana Kozáková
- Institute of Microbiology Czech Academy of Sciences Nový Hrádek Czech Republic
| | - Martin Schwarzer
- Institute of Microbiology Czech Academy of Sciences Nový Hrádek Czech Republic
| | - Mario Noti
- Institute of Pathology University of Bern Bern Switzerland
| | - Nicole Wit
- Wageningen Food and Biobased Research Wageningen The Netherlands
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El Hadad S, Zakareya A, Al-Hejin A, Aldahlawi A, Alharbi M. Sustaining exposure to high concentrations of bifidobacteria inhibits gene expression of Mouse's mucosal immunity. Heliyon 2019; 5:e02866. [PMID: 31890933 PMCID: PMC6926234 DOI: 10.1016/j.heliyon.2019.e02866] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 07/23/2019] [Accepted: 11/12/2019] [Indexed: 12/28/2022] Open
Abstract
Numerous dietary products are supplemented with probiotics that may be beneficial for human health. Recently, bifidobacteria have received increasing attention as a genus of probiotic bacteria with high efficiency and few side effects. To examine potential effects of different bifidobacteria concentrations on the mucosal immune response, we fed mice with (a) 108 colony-forming units (CFU) of bifidobacteria (group 108B), and (b) with 1012 CFU of bifidobacteria (group 1012B) over 42 days and assessed gene expression in intestinal mucosa and immune marker concentrations in serum samples; ten untreated female mice were used as a control. Continuous exposure to 108 CFU of bifidobacteria activated both macrophages and Treg immune cells through significantly increasing the expression of mucosal TLR2 and IL10-mRNA genes, but inhibited Th1 and Th2 cells via significant downregulation of IL4 and IFNγ gene expression, compared to untreated mice. Interestingly, group 1012B showed down-regulated expression of TLR2, IL10, and IL4 genes but up-regulated expression of IFNγ, compared to group 108B and to the control. Also, polyclonal immunoglobulins IgG, IgM, and IgA showed a significant increase in all treated mice compared to the control. We conclude that high concentrations of bifidobacteria reduced innate immune functions. Furthermore, adaptive immunity seemed to be enhanced by increasing stimulation of T and B lymphocytes, suggesting aberration of the immune system following intestinal inflammation due to constant exposure to high concentrations of bifidobacteria. Both experimental bifidobacteria concentrations increased the total levels of circulating Igs, particularly of IgA.
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Affiliation(s)
- Sahar El Hadad
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.,Research Center of Genetic Engineering and Bioinformatics, VACSERA, Cairo, Egypt.,Immunolgy Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ayeshah Zakareya
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ahmed Al-Hejin
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.,Microbiology Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Alia Aldahlawi
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.,Immunolgy Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.,Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mona Alharbi
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
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Kim R, Attayek PJ, Wang Y, Furtado KL, Tamayo R, Sims CE, Allbritton NL. An in vitro intestinal platform with a self-sustaining oxygen gradient to study the human gut/microbiome interface. Biofabrication 2019; 12:015006. [PMID: 31519008 PMCID: PMC6933551 DOI: 10.1088/1758-5090/ab446e] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
An oxygen gradient formed along the length of colonic crypts supports stem-cell proliferation at the normoxic crypt base while supporting obligate anaerobe growth in the anoxic colonic lumen. Primary human colonic epithelial cells derived from human gastrointestinal stem cells were cultured within a device possessing materials of tailored oxygen permeability to produce an oxygen-depleted luminal (0.8% ± 0.1% O2) and oxygen-rich basal (11.1% ± 0.5% O2) compartment. This oxygen difference created a stable oxygen gradient across the colonic epithelial cells which remained viable and properly polarized. Facultative and obligate anaerobes Lactobacillus rhamnosus, Bifidobacterium adolescentis, and Clostridium difficile grew readily within the luminal compartment. When formed along the length of an in vitro crypt, the oxygen gradient facilitated cell compartmentalization within the crypt by enhancing confinement of the proliferative cells to the crypt base. This platform provides a simple system to create a physiological oxygen gradient across an intestinal mimic while simultaneously supporting anaerobe co-culture.
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Affiliation(s)
- Raehyun Kim
- Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, North Carolina
| | - Peter J. Attayek
- Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, North Carolina
| | - Yuli Wang
- Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina
| | - Kathleen L. Furtado
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina
| | - Rita Tamayo
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina
| | - Christopher E. Sims
- Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina
| | - Nancy L. Allbritton
- Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, North Carolina
- Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina
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Yasuda S, Horinaka M, Sakai T. Sulforaphane enhances apoptosis induced by Lactobacillus pentosus strain S-PT84 via the TNFα pathway in human colon cancer cells. Oncol Lett 2019; 18:4253-4261. [PMID: 31579089 DOI: 10.3892/ol.2019.10739] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Accepted: 05/29/2019] [Indexed: 01/07/2023] Open
Abstract
Sulforaphane and Lactobacilli induce apoptosis in several cancer cells. Sulforaphane, a dietary isothiocyanate, is an attractive agent due to its potent anticancer effects. Sulforaphane suppresses the proliferation of various cancer cells in vitro and in vivo. The present study investigated the effect of sulforaphane and a co-culture with Lactobacillus-treated peripheral blood mononuclear cells (PBMCs) in human colon cancer cells. The combination markedly induced apoptosis in human colon cancer HCT116 and SW480 cells. A pan-caspase inhibitor markedly inhibited apoptosis, and a tumor necrosis factor (TNF) receptor/Fc chimera partially inhibited apoptosis in both cells. The amount of TNFα secretion in the culture supernatant was significantly increased by co-culture with Lactobacillus-treated normal human PBMCs. On the other hand, the expression of cellular inhibitor of apoptosis-2 (cIAP-2), an anti-apoptotic protein, was increased by co-culture with Lactobacillus-treated PBMCs in colon cancer cells, but sulforaphane treatment significantly suppressed the induction of cIAP-2. The present results revealed that sulforaphane enhances apoptosis in human colon cancer cells under co-culture with Lactobacillus-treated PBMCs via the TNFα signaling pathway.
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Affiliation(s)
- Shusuke Yasuda
- Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan
| | - Mano Horinaka
- Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan
| | - Toshiyuki Sakai
- Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto 602-8566, Japan
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Zhang JS, Corredig M, Morales-Rayas R, Hassan A, Griffiths MW, LaPointe G. Downregulation of Salmonella Virulence Gene Expression During Invasion of Epithelial Cells Treated with Lactococcus lactis subsp. cremoris JFR1 Requires OppA. Probiotics Antimicrob Proteins 2019; 12:577-588. [PMID: 31377945 DOI: 10.1007/s12602-019-09574-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Invasion of Salmonella into host intestinal epithelial cells requires the expression of virulence genes. In this study, cell culture models of human intestinal cells (mucus-producing HT29-MTX cells, absorptive Caco-2 cells, and combined cocultures of the two) were used to determine the effects of Lactococcus lactis subsp. cremoris treatments (exopolysaccharide producing and nonproducing strains) on the virulence gene expression of Salmonella Typhimurium and its mutant lacking the oligopeptide permease subunit A (ΔoppA). During the course of epithelial cell (HT29-MTX, Caco-2, and combined) infection by Salmonella Typhimurium DT104, improved barrier function was reflected by increased transepithelial electrical resistance in cells treated with both strains of L. lactis subsp. cremoris. In addition, virulence gene expression was downregulated, accompanied with lower numbers of invasive bacteria into epithelial cells in the presence of L. lactis subsp. cremoris treatments. Similarly, virulence gene expression of Salmonella was also suppressed when coincubated with overnight cultures of both L. lactis subsp. cremoris strains in the absence of epithelial cells. However, in medium or in the presence of cell cultures, Salmonella lacking the OppA permease function remained virulent. HT29-MTX cells and combined cultures stimulated by Salmonella Typhimurium DT104 showed significantly lower secretion levels of pro-inflammatory cytokine IL-8 after treatment with L. lactis subsp. cremoris cell suspensions. Contrarily, these responses were not observed during infection with S. Typhimurium ΔoppA. Both the exopolysaccharide producing and nonproducing strains of L. lactis subsp. cremoris JFR1 exhibited an antivirulence effect against S. Typhimurium DT104 although no significant difference between the two strains was observed. Our results show that an intact peptide transporter is essential for the suppression of Salmonella virulence genes which leads to the protection of the barrier function in the cell culture models studied.
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Affiliation(s)
- J S Zhang
- Canadian Research Institute for Food Safety, Department of Food Science, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | - M Corredig
- Department of Food Science, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | - R Morales-Rayas
- Canadian Research Institute for Food Safety, Department of Food Science, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | - A Hassan
- Daisy Brand, Dallas, TX, 75251, USA
| | - M W Griffiths
- Canadian Research Institute for Food Safety, Department of Food Science, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | - Gisèle LaPointe
- Canadian Research Institute for Food Safety, Department of Food Science, University of Guelph, Guelph, ON, N1G 2W1, Canada.
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Ashford MA, Palackdharry SM, Sadd BM, Bowden RM, Vogel LA. Intestinal B cells in the red-eared slider turtle, Trachemys scripta: Anatomical distribution and implications for ecological interactions with pathogenic microbes. JOURNAL OF EXPERIMENTAL ZOOLOGY PART 2019; 331:407-415. [PMID: 31328906 DOI: 10.1002/jez.2307] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/05/2019] [Accepted: 06/13/2019] [Indexed: 12/17/2022]
Abstract
Disease is a significant threat in the global decline of reptile species. Many aquatic reptiles live in habitats with high levels of opportunistic microbial pathogens, yet little is known about their immune system. Gut-associated lymphoid tissue is vital for protection against ingested pathogens and maintenance of normal gut microbiota. In mammals, gut mucosal immunity is well-characterized and mucosal surfaces are coated in protective antibodies. However, reptiles lack lymph nodes and Peyer's patches, which are the major sites of mammalian B cell responses. The presence or distribution of mucosal B cells in reptiles is unknown. In this study, we first set out to determine if B cells could be detected in intestinal tissues of red-eared slider turtles, Trachemys scripta. Using whole-mount immunochemistry and a primary antibody to turtle antibody light chains, we identified widely distributed B cell aggregates within the small intestine of hatchling turtles. These aggregates appeared similar to isolated lymphoid follicles (ILFs) in mammals and the frequency was much higher in distal intestinal sections than in proximal sections. To determine if these structures were inducible in the presence of microbes, we introduced an enteric Salmonella species through oral gavage. Analysis of intestinal tissues revealed that hatchlings exposed to Salmonella exhibited significantly more of these aggregates when compared with those that did not receive bacteria. These studies provide the first evidence for B cell-containing ILF-like structures in reptiles and provide novel information about gut immunity in nonmammalian vertebrates that could have important implications for ecological interactions with pathogens.
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Affiliation(s)
- Marc A Ashford
- School of Biological Sciences, Illinois State University, Normal, IIlinois
| | | | - Ben M Sadd
- School of Biological Sciences, Illinois State University, Normal, IIlinois
| | - Rachel M Bowden
- School of Biological Sciences, Illinois State University, Normal, IIlinois
| | - Laura A Vogel
- School of Biological Sciences, Illinois State University, Normal, IIlinois
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Fritsch J, Abreu MT. The Microbiota and the Immune Response: What Is the Chicken and What Is the Egg? Gastrointest Endosc Clin N Am 2019; 29:381-393. [PMID: 31078242 DOI: 10.1016/j.giec.2019.02.005] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The underlying factors driving the onset and progression of inflammatory bowel disease (IBD) include the interplay between host genetics, microbiota, and mucosal inflammation. The same environmental triggers that are a risk factor for IBD also alter the microbiota, suggesting a link between the microbiome and IBD. Specific IBD-associated genetic polymorphisms change the microbiome linking host genetics to the microbiota. Microbial changes occur at least simultaneously with new onset IBD, and fecal microbial transplant can ameliorate certain types of IBD. A current debate in the field is which comes first, dysbiosis or inflammation? Can restitution of the microbiome "cure" IBD?
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Affiliation(s)
- Julia Fritsch
- Microbiology and Immunology, Center for Crohn's and Colitis, University of Miami Miller School of Medicine, 1011 North West 15th Street (D-149), Gautier Building, Suite 537B, Miami, FL USA
| | - Maria T Abreu
- Department of Medicine, Division of Gastroenterology, Crohn's & Colitis Center, University of Miami Miller School of Medicine, 1011 North West 15th Street (D-149), Gautier Building, Suite 510, Miami, FL USA.
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50
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Ambrosini YM, Borcherding D, Kanthasamy A, Kim HJ, Willette AA, Jergens A, Allenspach K, Mochel JP. The Gut-Brain Axis in Neurodegenerative Diseases and Relevance of the Canine Model: A Review. Front Aging Neurosci 2019; 11:130. [PMID: 31275138 PMCID: PMC6591269 DOI: 10.3389/fnagi.2019.00130] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 05/16/2019] [Indexed: 12/13/2022] Open
Abstract
Identifying appropriate animal models is critical in developing translatable in vitro and in vivo systems for therapeutic drug development and investigating disease pathophysiology. These animal models should have direct biological and translational relevance to the underlying disease they are supposed to mimic. Aging dogs not only naturally develop a cognitive decline in many aspects including learning and memory deficits, but they also exhibit human-like individual variability in the aging process. Neurodegenerative processes that can be observed in both human and canine brains include the progressive accumulation of β-amyloid (Aβ) found as diffuse plaques in the prefrontal cortex (PFC), including the gyrus proreus (i.e., medial orbital PFC), as well as the hippocampus and the cerebral vasculature. Tau pathology, a marker of neurodegeneration and dementia progression, was also found in canine hippocampal synapses. Various epidemiological data show that human patients with neurodegenerative diseases have concurrent intestinal lesions, and histopathological changes in the gastrointestinal (GI) tract occurs decades before neurodegenerative changes. Gut microbiome alterations have also been reported in many neurodegenerative diseases including Alzheimer's (AD) and Parkinson's diseases, as well as inflammatory central nervous system (CNS) diseases. Interestingly, the dog gut microbiome more closely resembles human gut microbiome in composition and functional overlap compared to rodent models. This article reviews the physiology of the gut-brain axis (GBA) and its involvement with neurodegenerative diseases in humans. Additionally, we outline the advantages and weaknesses of current in vitro and in vivo models and discuss future research directions investigating major human neurodegenerative diseases such as AD and Parkinson's diseases using dogs.
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Affiliation(s)
- Yoko M. Ambrosini
- Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Dana Borcherding
- Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Anumantha Kanthasamy
- Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
| | - Hyun Jung Kim
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States
| | - Auriel A. Willette
- Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
- Department of Food Science and Human Nutrition, College of Agriculture and Life Sciences, Iowa State University, Ames, IA, United States
| | - Albert Jergens
- Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA, United States
| | - Karin Allenspach
- Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA, United States
| | - Jonathan P. Mochel
- Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States
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