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Liu J, Dai Y, Yang W, Chen ZY. Role of Mushroom Polysaccharides in Modulation of GI Homeostasis and Protection of GI Barrier. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2025; 73:6416-6441. [PMID: 40063730 PMCID: PMC11926878 DOI: 10.1021/acs.jafc.5c00745] [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: 03/20/2025]
Abstract
Edible and medicinal mushroom polysaccharides (EMMPs) have been widely studied for their various biological activities. It has been shown that EMMPs could modulate microbiota in the large intestine and improve intestinal health. However, the role of EMMPs in protecting the gastric barrier, regulating gastric microbiota, and improving gastric health cannot be ignored. Hence, this review will elucidate the effect of EMMPs on gastric and intestinal barriers, with emphasis on the interaction of EMMPs with microbiota in maintaining overall gastrointestinal health. Additionally, this review highlights the gastroprotective effects and underlying mechanisms of EMMPs against gastric mucosa injury, gastritis, gastric ulcer, and gastric cancer. Furthermore, the effects of EMMPs on intestinal diseases, including inflammatory bowel disease, colorectal cancer, and intestinal infection, are also summarized. This review will also discuss the future perspective and challenges in the use of EMMPs as a dietary supplement or a nutraceutical in preventing and treating gastrointestinal diseases.
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Affiliation(s)
- Jianhui Liu
- Collaborative Innovation Center for Modern Grain Circulation and Safety, Jiangsu Province Engineering Research Center of Edible Fungus Preservation and Intensive Processing, College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China
- School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong 999077, China
| | - Yi Dai
- Collaborative Innovation Center for Modern Grain Circulation and Safety, Jiangsu Province Engineering Research Center of Edible Fungus Preservation and Intensive Processing, College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China
| | - Wenjian Yang
- Collaborative Innovation Center for Modern Grain Circulation and Safety, Jiangsu Province Engineering Research Center of Edible Fungus Preservation and Intensive Processing, College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China
| | - Zhen-Yu Chen
- School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong 999077, China
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2
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Liu S, Zeng X, Li J, Li W, Gu Y, Li B, Wang J. Goat milk oligosaccharides: regulating infant immunity by intervention in the gut microbiota. Food Funct 2025; 16:2213-2229. [PMID: 40035489 DOI: 10.1039/d5fo00162e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
The health status of the growing infant is closely related to the development of the gut microbiota during infancy, which is also a major stimulator of the immune system. Goat milk oligosaccharides (gMOs) are a class of bioactive compounds in goat milk, which have attracted extensive research interest in recent years. Recent studies have highlighted that gMOs as prebiotics can regulate the gut microbiota, exhibit multiple health effects, and act as immunomodulators. This article outlines the structure, classification, and functions of gMOs. In addition, we also deeply explored the mechanism of gMO interaction with infant gut microbiota and regulation of infant immunity. Finally, the possibility of gMOs as an effective substitute for natural prebiotics in breast milk is revisited. We concluded that gMOs improve infant immune function by regulating intestinal beneficial bacteria (Bifidobacteria, Lactobacilli, etc.) and their metabolism. Therefore, gMOs are significant to infant immune health and are expected to become a substitute for human milk oligosaccharides (HMOs).
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Affiliation(s)
- Sibo Liu
- Food College, Northeast Agricultural University, Harbin 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China
| | - Xiaoling Zeng
- Ausnutria Dairy (China) Co., Ltd, Changsha 410000, China.
| | - Jing Li
- Ausnutria Dairy (China) Co., Ltd, Changsha 410000, China.
| | - Wei Li
- Ausnutria Dairy (China) Co., Ltd, Changsha 410000, China.
| | - Yue Gu
- Food College, Northeast Agricultural University, Harbin 150030, China.
| | - Bailiang Li
- Food College, Northeast Agricultural University, Harbin 150030, China.
- Key Laboratory of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin 150030, China
| | - Jiaqi Wang
- Ausnutria Dairy (China) Co., Ltd, Changsha 410000, China.
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Yu L, Lin F, Yu Y, Deng X, Shi X, Lu X, Lu Y, Wang D. Rehmannia glutinosa polysaccharides enhance intestinal immunity of mice through regulating the microbiota. Int J Biol Macromol 2024; 283:137878. [PMID: 39571844 DOI: 10.1016/j.ijbiomac.2024.137878] [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: 04/03/2024] [Revised: 11/16/2024] [Accepted: 11/18/2024] [Indexed: 11/26/2024]
Abstract
The Rehmannia glutinosa polysaccharides (RGP) have various benefits such as enhancing immune cell activity, decreasing oxidative stress and delaying or inhibiting tumor occurrence. Although much research has been directed at understanding the role of RGP, its influence on gut immunity is largely understudied. Here, we aimed to dissect the immune-regulating effects of RGP in the mice intestines. In vivo experiments involving the oral administration of RGP to mice at dosages of 100, 200, and 400 mg/kg over seven consecutive days revealed that RGP therapy significantly increased the percentages of CD3+ T lymphocytes and CD19+ B lymphocytes in intestines and improved the integrity of the mucosal barrier. Moreover, RGP modified the gut microbiota composition by enhancing the abundance of beneficial bacteria like Lactobacillus and Akkermansia. Fecal microbiota transplantation (FMT) experiments further revealed that RGP modulated the host's intestinal immunological function by altering the gut microbiota composition. These findings indicate that RGP may control the immunological function of the intestines.
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Affiliation(s)
- Lin Yu
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Fangzhu Lin
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yaming Yu
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Xiangwen Deng
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Xiaofeng Shi
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Xuanqi Lu
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yu Lu
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China
| | - Deyun Wang
- Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
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4
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Gao P, Morita N, Shinkura R. Role of mucosal IgA antibodies as novel therapies to enhance mucosal barriers. Semin Immunopathol 2024; 47:1. [PMID: 39567378 PMCID: PMC11579142 DOI: 10.1007/s00281-024-01027-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 11/10/2024] [Indexed: 11/22/2024]
Abstract
To prevent infection, the experience of the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic has led to recognition of the importance of not only vaccines but also the strengthening of mucosal barriers by secretory immunoglobulin A (IgA). Strong mucosal barrier provided by IgA is also possible to prevent allergies and chronic inflammatory conditions in the intestinal tract, since it can protect foreign enemies or antigens at the first line of defense before their invasion. Therefore, it is important to understand the role of IgA antibodies secreted by the mucosa of the body. In this section, we discuss the role of mucosal IgA antibodies in relation to three disease states: control of intestinal microbiota, protection against infection, and allergy. In addition, we provide the evidence in which the quality as well as the quantity of IgA is critical for disease prevention. Therefore, we discuss about novel strategies to enhance mucosal barriers by induction of high-quality IgA.
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Affiliation(s)
- Peng Gao
- Laboratory of Immunology and Infection Control, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo, 113-0032, Japan
| | - Naoki Morita
- Laboratory of Immunology and Infection Control, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo, 113-0032, Japan
| | - Reiko Shinkura
- Laboratory of Immunology and Infection Control, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-Ku, Tokyo, 113-0032, Japan.
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Camarini R, Marianno P, Hanampa-Maquera M, Oliveira SDS, Câmara NOS. Prenatal Stress and Ethanol Exposure: Microbiota-Induced Immune Dysregulation and Psychiatric Risks. Int J Mol Sci 2024; 25:9776. [PMID: 39337263 PMCID: PMC11431796 DOI: 10.3390/ijms25189776] [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: 06/14/2024] [Revised: 08/22/2024] [Accepted: 08/25/2024] [Indexed: 09/30/2024] Open
Abstract
Changes in maternal gut microbiota due to stress and/or ethanol exposure can have lasting effects on offspring's health, particularly regarding immunity, inflammation response, and susceptibility to psychiatric disorders. The literature search for this review was conducted using PubMed and Scopus, employing keywords and phrases related to maternal stress, ethanol exposure, gut microbiota, microbiome, gut-brain axis, diet, dysbiosis, progesterone, placenta, prenatal development, immunity, inflammation, and depression to identify relevant studies in both preclinical and human research. Only a limited number of reviews were included to support the arguments. The search encompassed studies from the 1990s to the present. This review begins by exploring the role of microbiota in modulating host health and disease. It then examines how disturbances in maternal microbiota can affect the offspring's immune system. The analysis continues by investigating the interplay between stress and dysbiosis, focusing on how prenatal maternal stress influences both maternal and offspring microbiota and its implications for susceptibility to depression. The review also considers the impact of ethanol consumption on gut dysbiosis, with an emphasis on the effects of prenatal ethanol exposure on both maternal and offspring microbiota. Finally, it is suggested that maternal gut microbiota dysbiosis may be significantly exacerbated by the combined effects of stress and ethanol exposure, leading to immune system dysfunction and chronic inflammation, which could increase the risk of depression in the offspring. These interactions underscore the potential for novel mental health interventions that address the gut-brain axis, especially in relation to maternal and offspring health.
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Affiliation(s)
- Rosana Camarini
- Department of Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo 05508-900, Brazil
| | - Priscila Marianno
- Department of Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo 05508-900, Brazil
| | - Maylin Hanampa-Maquera
- Department of Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo 05508-900, Brazil
| | - Samuel Dos Santos Oliveira
- Department of Immunology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo 05508-900, Brazil
| | - Niels Olsen Saraiva Câmara
- Department of Immunology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo 05508-900, Brazil
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Riehl L, Fürst J, Kress M, Rykalo N. The importance of the gut microbiome and its signals for a healthy nervous system and the multifaceted mechanisms of neuropsychiatric disorders. Front Neurosci 2024; 17:1302957. [PMID: 38249593 PMCID: PMC10797776 DOI: 10.3389/fnins.2023.1302957] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 12/13/2023] [Indexed: 01/23/2024] Open
Abstract
Increasing evidence links the gut microbiome and the nervous system in health and disease. This narrative review discusses current views on the interaction between the gut microbiota, the intestinal epithelium, and the brain, and provides an overview of the communication routes and signals of the bidirectional interactions between gut microbiota and the brain, including circulatory, immunological, neuroanatomical, and neuroendocrine pathways. Similarities and differences in healthy gut microbiota in humans and mice exist that are relevant for the translational gap between non-human model systems and patients. There is an increasing spectrum of metabolites and neurotransmitters that are released and/or modulated by the gut microbiota in both homeostatic and pathological conditions. Dysbiotic disruptions occur as consequences of critical illnesses such as cancer, cardiovascular and chronic kidney disease but also neurological, mental, and pain disorders, as well as ischemic and traumatic brain injury. Changes in the gut microbiota (dysbiosis) and a concomitant imbalance in the release of mediators may be cause or consequence of diseases of the central nervous system and are increasingly emerging as critical links to the disruption of healthy physiological function, alterations in nutrition intake, exposure to hypoxic conditions and others, observed in brain disorders. Despite the generally accepted importance of the gut microbiome, the bidirectional communication routes between brain and gut are not fully understood. Elucidating these routes and signaling pathways in more detail offers novel mechanistic insight into the pathophysiology and multifaceted aspects of brain disorders.
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Affiliation(s)
| | | | | | - Nadiia Rykalo
- Institute of Physiology, Department of Physiology and Medical Physics, Medical University Innsbruck, Innsbruck, Austria
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Sharma S, Kulkarni RR, Sharif S, Hassan H, Alizadeh M, Pratt S, Abdelaziz K. In ovo feeding of probiotic lactobacilli differentially alters expression of genes involved in the development and immunological maturation of bursa of Fabricius in pre-hatched chicks. Poult Sci 2024; 103:103237. [PMID: 38011819 PMCID: PMC10801656 DOI: 10.1016/j.psj.2023.103237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 10/10/2023] [Accepted: 10/23/2023] [Indexed: 11/29/2023] Open
Abstract
Compelling evidence indicates that immunological maturation of the gut-associated lymphoid tissues, including the bursa of Fabricius, is dependent upon antigenic stimulation post-hatch. In view of these data, the present study investigated the impact of exposing the immune system of chick embryos to antigenic stimuli, via in ovo delivery of poultry-specific lactobacilli, on the expression of genes associated with early bursal development and maturation. Broiler line embryonated eggs were inoculated with 106 and 107 colony-forming units (CFUs) of an individual or a mixture of Lactobacillus species, including L. crispatus (C25), L. animalis (P38), L. acidophilus (P42), and L. reuteri (P43), at embryonic day 18 (ED18). The bursa of Fabricius was collected from pre-hatched chicks (ED20) to measure the expression levels of various immune system genes. The results revealed that L. acidophilus and the mixture of Lactobacillus species at the dose of 106 CFU consistently elicited higher expression of genes responsible for B cell development, differentiation, and survival (B cell activating factor (BAFF), BAFF-receptor (BAFF-R)), and antibody production (interleukin (IL)-10) and diversification (TGF-β). Similar expression patterns were also noted in T helper (Th) cell-associated cytokine genes, including Th1-type cytokines (interferon (IFN)-γ and IL-12p40), Th2-type cytokines (IL-4 and IL-13) and Th17 cytokine (IL-17). Overall, these results suggest that the supplementation of poultry-specific lactobacilli to chick embryos might be beneficial for accelerating the development and immunological maturation of the bursa of Fabricius. However, further studies are required to determine if the changes in gene expression are associated with the developmental trajectory and phenotypes of bursal cells.
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Affiliation(s)
- Shreeya Sharma
- Department of Animal and Veterinary Sciences, College of Agriculture, Forestry and Life Sciences, Clemson University, Clemson, SC, USA
| | - Raveendra R Kulkarni
- Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC, USA
| | - Shayan Sharif
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada
| | - Hosni Hassan
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC, USA
| | - Mohammadali Alizadeh
- Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1, Canada
| | - Scott Pratt
- Department of Animal and Veterinary Sciences, College of Agriculture, Forestry and Life Sciences, Clemson University, Clemson, SC, USA
| | - Khaled Abdelaziz
- Department of Animal and Veterinary Sciences, College of Agriculture, Forestry and Life Sciences, Clemson University, Clemson, SC, USA.
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Batista-Liz JC, Calvo-Río V, Sebastián Mora-Gil M, Sevilla-Pérez B, Márquez A, Leonardo MT, Peñalba A, Carmona FD, Narvaez J, Martín-Penagos L, Belmar-Vega L, Gómez-Fernández C, Caminal-Montero L, Collado P, Quiroga-Colina P, Uriarte-Ecenarro M, Rubio E, Luque ML, Blanco-Madrigal JM, Galíndez-Agirregoikoa E, Martín J, Castañeda S, González-Gay MA, Blanco R, Pulito-Cueto V, López-Mejías R. Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis? Int J Mol Sci 2023; 24:13063. [PMID: 37685869 PMCID: PMC10488110 DOI: 10.3390/ijms241713063] [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: 08/04/2023] [Revised: 08/17/2023] [Accepted: 08/18/2023] [Indexed: 09/10/2023] Open
Abstract
ITGAM-ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM-ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.
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Affiliation(s)
- Joao Carlos Batista-Liz
- Immunopathology Group, Rheumatology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, 39011 Santander, Spain; (J.C.B.-L.); (V.C.-R.); (M.S.M.-G.); (R.B.)
| | - Vanesa Calvo-Río
- Immunopathology Group, Rheumatology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, 39011 Santander, Spain; (J.C.B.-L.); (V.C.-R.); (M.S.M.-G.); (R.B.)
| | - María Sebastián Mora-Gil
- Immunopathology Group, Rheumatology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, 39011 Santander, Spain; (J.C.B.-L.); (V.C.-R.); (M.S.M.-G.); (R.B.)
| | - Belén Sevilla-Pérez
- Division of Paediatrics, Hospital Universitario San Cecilio, 18016 Granada, Spain;
| | - Ana Márquez
- Instituto de Parasitología y Biomedicina ‘López-Neyra’, CSIC, PTS Granada, 18016 Granada, Spain; (A.M.); (J.M.)
| | - María Teresa Leonardo
- Division of Paediatrics, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain; (M.T.L.); (A.P.)
| | - Ana Peñalba
- Division of Paediatrics, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain; (M.T.L.); (A.P.)
| | - Francisco David Carmona
- Departamento de Genética e Instituto de Biotecnología, Centro de Investigación Biomédica (CIBM), Universidad de Granada, 18071 Granada, Spain;
- Instituto de Investigación Biosanitaria ibs. Granada, 18012 Granada, Spain
| | - Javier Narvaez
- Division of Rheumatology, Hospital Universitario de Bellvitge, 08907 Barcelona, Spain;
| | - Luis Martín-Penagos
- Immunopathology Group, Division of Nephrology, Hospital Universitario Marqués de Valdecilla-IDIVAL, 39011 Santander, Spain; (L.M.-P.); (L.B.-V.)
| | - Lara Belmar-Vega
- Immunopathology Group, Division of Nephrology, Hospital Universitario Marqués de Valdecilla-IDIVAL, 39011 Santander, Spain; (L.M.-P.); (L.B.-V.)
| | | | - Luis Caminal-Montero
- Internal Medicine Department, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain;
| | - Paz Collado
- Division of Rheumatology, Hospital Universitario Severo Ochoa, 28911 Madrid, Spain;
| | - Patricia Quiroga-Colina
- Division of Rheumatology, Hospital Universitario de La Princesa, IIS-Princesa, 28006 Madrid, Spain; (P.Q.-C.); (M.U.-E.); (S.C.)
| | - Miren Uriarte-Ecenarro
- Division of Rheumatology, Hospital Universitario de La Princesa, IIS-Princesa, 28006 Madrid, Spain; (P.Q.-C.); (M.U.-E.); (S.C.)
| | - Esteban Rubio
- Department of Rheumatology, Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain; (E.R.); (M.L.L.)
| | - Manuel León Luque
- Department of Rheumatology, Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain; (E.R.); (M.L.L.)
| | - Juan María Blanco-Madrigal
- Division of Rheumatology, Hospital Universitario de Basurto, 48013 Bilbao, Spain; (J.M.B.-M.); (E.G.-A.)
| | - Eva Galíndez-Agirregoikoa
- Division of Rheumatology, Hospital Universitario de Basurto, 48013 Bilbao, Spain; (J.M.B.-M.); (E.G.-A.)
| | - Javier Martín
- Instituto de Parasitología y Biomedicina ‘López-Neyra’, CSIC, PTS Granada, 18016 Granada, Spain; (A.M.); (J.M.)
| | - Santos Castañeda
- Division of Rheumatology, Hospital Universitario de La Princesa, IIS-Princesa, 28006 Madrid, Spain; (P.Q.-C.); (M.U.-E.); (S.C.)
| | - Miguel Angel González-Gay
- Department of Rheumatology, IIS-Fundación Jiménez Díaz, 28040 Madrid, Spain;
- School of Medicine, Universidad de Cantabria, 39011 Santander, Spain
| | - Ricardo Blanco
- Immunopathology Group, Rheumatology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, 39011 Santander, Spain; (J.C.B.-L.); (V.C.-R.); (M.S.M.-G.); (R.B.)
| | - Verónica Pulito-Cueto
- Immunopathology Group, Rheumatology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, 39011 Santander, Spain; (J.C.B.-L.); (V.C.-R.); (M.S.M.-G.); (R.B.)
| | - Raquel López-Mejías
- Immunopathology Group, Rheumatology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, 39011 Santander, Spain; (J.C.B.-L.); (V.C.-R.); (M.S.M.-G.); (R.B.)
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Cao Y, Teng Y, Liu H, Li J, Zhu B, Xia X. Rhopilema esculentum polysaccharides enhance epithelial cell barrier in vitro and alleviate chronic colitis in mice. Int J Biol Macromol 2023; 241:124560. [PMID: 37088192 DOI: 10.1016/j.ijbiomac.2023.124560] [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] [Received: 10/04/2022] [Revised: 04/10/2023] [Accepted: 04/18/2023] [Indexed: 04/25/2023]
Abstract
The purposes of this study were to characterize polysaccharides from Rhopilema esculentum and to explore their impacts on gut barrier function and inflammation in vitro and in mice with chronic colitis triggered by long-term administration of dextran sulfate sodium (DSS). Two polysaccharides were isolated and purified from Rhopilema esculentum, named REP-1 and REP-2. REP-1 with a molecular weight of 8.21 kDa was composed of mannose, glucosamine, galactosamine, glucose, galactose, and arabinose with a molar ratio of 0.04:0.03:0.38:1:1.36:0.06, and REP-2 with a molecular weight of 10.11 kDa mainly consisted of mannose, glucuronic acid, galactosamine, glucose, galactose, and arabinose with a molar ratio of 0.04:0.12:0.41:1:1.2:0.06. Compared to REP-1, REP-2 displayed better ability to up-regulate the expression of genes related to tight junctions and mucus in LPS-stimulated Caco-2 cells and better immunomodulatory activities in RAW264.7 macrophages. Then mice experiments showed that REP-2 efficiently attenuated the symptoms of colitis, decreased the secretion of pro-inflammatory cytokines, and restored intestinal barrier function in mice with chronic colitis. These results demonstrate that REP-2 might be a promising agent for protecting intestinal and mucus barrier and mitigating inflammation-associated intestinal diseases such as ulcerative colitis.
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Affiliation(s)
- Yu Cao
- State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Yue Teng
- State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, China
| | - Huanhuan Liu
- State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, China
| | - Jiahui Li
- State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, China
| | - Beiwei Zhu
- State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
| | - Xiaodong Xia
- State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, China.
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10
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Sun Y, Ho CT, Zhang X. Neuroprotection of Food Bioactives in Neurodegenerative Diseases: Role of the Gut Microbiota and Innate Immune Receptors. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:2718-2733. [PMID: 36700657 DOI: 10.1021/acs.jafc.2c07742] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Gut-brain connections may be mediated by an assortment of microbial molecules, which can subsequently traverse intestinal and blood-brain barriers and impact neurological function. Pattern recognition receptors (PRRs) are important innate immune proteins in the gut. Gut microbiota act in concert with the PRRs is a novel target for regulating host-microbe signaling and immune homeostasis, which may involve the pathogenesis of neurodegenerative diseases. Natural food bioactives bestow a protective advantage on neurodegenerative diseases through immunomodulatory effects of the modified gut microbiota or alterations in the landscape of microbiota-produced metabolites via PRRs modulation. In this review, we discuss the effect of natural food bioactives on the gut microbiota and the role of PRRs in the gut-brain crosstalk. We focused on the neuroprotective mechanisms of natural bioactive compounds behind the action of the gut microbiota and PRRs. Research advances in natural food bioactives as antineurodegeneration agents were also presented.
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Affiliation(s)
- Ying Sun
- Department of Food Science and Engineering, Ningbo University, Ningbo 315211, P.R. China
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901, United States
| | - Xin Zhang
- Department of Food Science and Engineering, Ningbo University, Ningbo 315211, P.R. China
- State Key Laboratory for Quality and Safety of Agro-products, Ningbo University, Ningbo 315211, P.R. China
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11
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Liu JP, Wang J, Zhou SX, Huang DC, Qi GH, Chen GT. Ginger polysaccharides enhance intestinal immunity by modulating gut microbiota in cyclophosphamide-induced immunosuppressed mice. Int J Biol Macromol 2022; 223:1308-1319. [PMID: 36395935 DOI: 10.1016/j.ijbiomac.2022.11.104] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 11/10/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022]
Abstract
In this study, the immunity-enhancing effect of ginger polysaccharides UGP1 and UGP2 on CTX-induced immunosuppressed mice was evaluated. The results showed that ginger polysaccharide could effectively alleviate the symptoms of weight loss and dietary intake reduction induced by CTX, increase fecal water content, reduce fecal pH, and protect immune organs of immunosuppressed mice. In addition, ginger polysaccharides also stimulated the secretion of cytokines IL-2, IL-4, TNF-α and immunoglobulin Ig-G in the serum of mice, increased the expression of Occludin and Claudin-1, and restored the level of short-chain fatty acids in the intestine to improve immune deficiency. Furthermore, ginger polysaccharides significantly reduced the relative abundance ratio of the Firmicutes and Bacteroidetes in mice and increased the relative abundance of Verrucomicrobia and Bacteroidetes at the phylum level. At the family level, ginger polysaccharides increased the relative abundance of beneficial bacteria such as Muribaculaceae, Bacteroidaceae and Lactobacillaceae, and decreased the relative abundance of harmful bacteria such as Rikenellaceae and Lachnospiraceae. Spearman correlation analysis indicated that ginger polysaccharides could enhance intestinal immunity by modulating gut microbiota associated with immune function. These results indicated that ginger polysaccharides have the potential to be a functional food ingredients or a natural medicine for the treatment of intestinal barrier injury.
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Affiliation(s)
- Jun-Ping Liu
- College of Engineering/National R&D Center for Chinese Herbal Medicine Processing, China Pharmaceutical University, Nanjing, 211198, China
| | - Jie Wang
- College of Engineering/National R&D Center for Chinese Herbal Medicine Processing, China Pharmaceutical University, Nanjing, 211198, China
| | - Si-Xuan Zhou
- College of Engineering/National R&D Center for Chinese Herbal Medicine Processing, China Pharmaceutical University, Nanjing, 211198, China
| | - De-Chun Huang
- College of Engineering/National R&D Center for Chinese Herbal Medicine Processing, China Pharmaceutical University, Nanjing, 211198, China
| | - Guo-Hong Qi
- College of Engineering/National R&D Center for Chinese Herbal Medicine Processing, China Pharmaceutical University, Nanjing, 211198, China.
| | - Gui-Tang Chen
- College of Engineering/National R&D Center for Chinese Herbal Medicine Processing, China Pharmaceutical University, Nanjing, 211198, China.
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12
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M cells of mouse and human Peyer's patches mediate the lymphatic absorption of an Astragalus hyperbranched heteroglycan. Carbohydr Polym 2022; 296:119952. [DOI: 10.1016/j.carbpol.2022.119952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/16/2022] [Accepted: 08/01/2022] [Indexed: 11/21/2022]
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13
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Huo J, Wu Z, Sun W, Wang Z, Wu J, Huang M, Wang B, Sun B. Protective Effects of Natural Polysaccharides on Intestinal Barrier Injury: A Review. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:711-735. [PMID: 35078319 DOI: 10.1021/acs.jafc.1c05966] [Citation(s) in RCA: 84] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Owing to their minimal side effects and effective protection from oxidative stress, inflammation, and malignant growth, natural polysaccharides (NPs) are a potential adjuvant therapy for several diseases caused by intestinal barrier injury (IBI). More studies are accumulating on the protective effects of NPs with respect to IBI, but the underlying mechanisms remain unclear. Thus, this review aims to represent current studies that investigate the protective effects of NPs on IBI by directly maintaining intestinal epithelial barrier integrity (inhibiting oxidative stress, regulating inflammatory cytokine expression, and increasing tight junction protein expression) and indirectly regulating intestinal immunity and microbiota. Furthermore, the mechanisms underlying IBI development are briefly introduced, and the structure-activity relationships of polysaccharides with intestinal barrier protection effects are discussed. Potential developments and challenges associated with NPs exhibiting protective effects against IBI have also been highlighted to guide the application of NPs in the treatment of intestinal diseases caused by IBI.
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Affiliation(s)
- Jiaying Huo
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, People's Republic of China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, People's Republic of China
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong 510640, People's Republic of China
| | - Ziyan Wu
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, People's Republic of China
- College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, People's Republic of China
| | - Weizheng Sun
- School of Food Science and Engineering, South China University of Technology, Guangzhou, Guangdong 510640, People's Republic of China
| | - Zhenhua Wang
- Center for Mitochondria and Healthy Aging, College of Life Science, Yantai University, Yantai, Shandong 264005, People's Republic of China
| | - Jihong Wu
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, People's Republic of China
- College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, People's Republic of China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, People's Republic of China
| | - Mingquan Huang
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, People's Republic of China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, People's Republic of China
| | - Bowen Wang
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, People's Republic of China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, People's Republic of China
| | - Baoguo Sun
- Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology and Business University, Beijing 100048, People's Republic of China
- Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, People's Republic of China
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Kapoor K, Eissa N, Tshikudi D, Bernstein CN, Ghia JE. Impact of intrarectal chromofungin treatment on dendritic cells-related markers in different immune compartments in colonic inflammatory conditions. World J Gastroenterol 2021; 27:8138-8155. [PMID: 35068859 PMCID: PMC8704268 DOI: 10.3748/wjg.v27.i47.8138] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 05/12/2021] [Accepted: 12/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chromofungin (CHR: chromogranin-A 47-66) is a chromogranin-A derived peptide with anti-inflammatory and anti-microbial properties. Ulcerative colitis (UC) is characterized by a colonic decrease of CHR and a dysregulation of dendritic CD11c+ cells.
AIM To investigate the association between CHR treatment and dendritic cells (DCs)-related markers in different immune compartments in colitis.
METHODS A model of acute UC-like colitis using dextran sulphate sodium (DSS) was used in addition to biopsies collected from UC patients.
RESULTS Intrarectal CHR treatment reduced the severity of DSS-induced colitis and was associated with a significant decrease in the expression of CD11c, CD40, CD80, CD86 and interleukin (IL)-12p40 in the inflamed colonic mucosa and CD11c, CD80, CD86 IL-6 and IL-12p40 within the mesenteric lymph nodes and the spleen. Furthermore, CHR treatment decreased CD80 and CD86 expression markers of splenic CD11c+ cells and decreased NF-κB expression in the colon and of splenic CD11c+ cells. In vitro, CHR decreased CD40, CD80, CD86 IL-6 and IL-12p40 expression in naïve bone marrow-derived CD11c+ DCs stimulated with lipopolysaccharide. Pharmacological studies demonstrated an impact of CHR on the NF-κB pathway. In patients with active UC, CHR level was reduced and showed a negative linear relationship with CD11c and CD86.
CONCLUSION CHR has protective properties against intestinal inflammation via the regulation of DC-related markers and CD11c+ cells. CHR could be a potential therapy of UC.
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Affiliation(s)
- Kunal Kapoor
- Department of Immunology, University of Manitoba, Winnipeg R3E0T5, MB, Canada
| | - Nour Eissa
- Department of Immunology, University of Manitoba, Winnipeg R3E0T5, MB, Canada
- Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg R3E0T5, MB, Canada
- Section of Gastroenterology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg R3E0T5, MB, Canada
- University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg R3E0T5, MB, Canada
| | - Diane Tshikudi
- Department of Immunology, University of Manitoba, Winnipeg R3E0T5, MB, Canada
| | - Charles N Bernstein
- Section of Gastroenterology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg R3E0T5, MB, Canada
- University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg R3E0T5, MB, Canada
| | - Jean-Eric Ghia
- Department of Immunology, University of Manitoba, Winnipeg R3E0T5, MB, Canada
- Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg R3E0T5, MB, Canada
- Section of Gastroenterology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg R3E0T5, MB, Canada
- University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg R3E0T5, MB, Canada
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15
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Xu Q, Shen M, Han Y, Diao H. Effects of Ellagic Acid Supplementation on Jejunal Morphology, Digestive Enzyme Activities, Antioxidant Capacity, and Microbiota in Mice. Front Microbiol 2021; 12:793576. [PMID: 34956161 PMCID: PMC8692252 DOI: 10.3389/fmicb.2021.793576] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 11/01/2021] [Indexed: 11/13/2022] Open
Abstract
Ellagic acid (EA), a plant polyphenol mainly found in nuts and fruits, exhibits various biological effects. However, the effects of EA on intestinal health remain poorly understood. Hence, the present study aimed to assess the effects of EA supplementation on jejunal morphology, digestive enzyme activities, antioxidant capacity, and microbiota in C57BL/6J mice. A total of 144 mice were randomly assigned to three treatments groups: the control (CON) group received a standard pellet diet, the 0.1% EA group received a standard pellet diet plus 0.1% EA, and the 0.3% EA group received a standard pellet diet plus 0.3% EA. The mice were killed at the end of the experimental period, and jejunal samples were collected. The results revealed that the mice in the 0.3% EA group had higher (P < 0.05) average daily gain and greater (P < 0.05) jejunal villus height than those in the CON group. In addition, the jejunal lactase and sucrase activities were higher (P < 0.05) in the 0.1% EA and 0.3% EA groups, and the alkaline phosphatase activity was higher (P < 0.05) in the 0.3% EA group than in the CON group. Compared with the CON group, the administration of EA increased (P < 0.05) the superoxide dismutase and catalase activities but decreased (P < 0.05) the malonaldehyde content in the jejunum. Moreover, the jejunal messenger RNA expression levels of nuclear factor-E2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1) were higher (P < 0.05) in the 0.3% EA group than in the CON group. Furthermore, compared with the CON group, the count of Escherichia coli decreased (P < 0.05), and that of Lactobacillus species increased (P < 0.05) in the 0.3% EA group. In general, our findings indicate that the administration of EA can enhance the growth of mice, promote intestinal development, increase the antioxidant capacity, and regulate the intestinal microbiota.
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Affiliation(s)
- Qiuying Xu
- Sichuan Nursing Vocational College, Chengdu, China
| | - Mingkang Shen
- School of the 1st Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Yuxin Han
- School of Nursing, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hui Diao
- Animal Breeding and Genetics Key Laboratory of Sichuan Province, Sichuan Academy of Animal Science, Chengdu, China
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16
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Tong L, Hao H, Zhang Z, Lv Y, Liang X, Liu Q, Liu T, Gong P, Zhang L, Cao F, Pastorin G, Lee CN, Chen X, Wang JW, Yi H. Milk-derived extracellular vesicles alleviate ulcerative colitis by regulating the gut immunity and reshaping the gut microbiota. Theranostics 2021; 11:8570-8586. [PMID: 34373759 PMCID: PMC8344018 DOI: 10.7150/thno.62046] [Citation(s) in RCA: 149] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 07/13/2021] [Indexed: 12/14/2022] Open
Abstract
Rationale: Bovine milk constitutes an essential part of human diet, especially for children, due to its enrichment of various nutrients. We recently developed an effective protocol for the isolation of extracellular vesicles from milk (mEVs) and discovered that mEVs contained large amounts of immune-active proteins and modulated the gut immunity and microbiota in healthy mice. Here, we aimed to explore the therapeutic effects of mEVs on inflammatory bowel disease. Methods: MicroRNAs and protein content in mEVs were analyzed by RNA sequencing and proteomics, respectively, followed by functional annotation. Ulcerative colitis (UC) was induced by feeding mice with dextran sulfate sodium. Intestinal immune cell populations were phenotyped by flow cytometry, and the gut microbiota was analyzed via 16S rRNA sequencing. Results: We showed that abundant proteins and microRNAs in mEVs were involved in the regulation of immune and inflammatory pathways and that oral administration of mEVs prevented colon shortening, reduced intestinal epithelium disruption, inhibited infiltration of inflammatory cells and tissue fibrosis in a mouse UC model. Mechanistically, mEVs attenuated inflammatory response via inhibiting TLR4-NF-κB signaling pathway and NLRP3 inflammasome activation. Furthermore, mEVs were able to correct cytokine production disorder and restore the balance between T helper type 17 (Th17) cells and interleukin-10+Foxp3+ regulatory T (Treg) cells in the inflamed colon. The disturbed gut microbiota in UC was also partially recovered upon treatment with mEVs. The correlation between the gut microbiota and cytokines suggests that mEVs may modulate intestinal immunity via influencing the gut microbiota. Conclusions: These findings reveal that mEVs alleviate colitis by regulating intestinal immune homeostasis via inhibiting TLR4-NF-κB and NLRP3 signaling pathways, restoring Treg/Th17 cell balance, and reshaping the gut microbiota.
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Affiliation(s)
- Lingjun Tong
- College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. China
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore
| | - Haining Hao
- College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. China
| | - Zhe Zhang
- College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. China
| | - Youyou Lv
- College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. China
| | - Xi Liang
- College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. China
| | - Qiqi Liu
- College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. China
| | - Tongjie Liu
- College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. China
| | - Pimin Gong
- College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. China
| | - Lanwei Zhang
- College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. China
| | - Fangfang Cao
- Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore
| | - Giorgia Pastorin
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore
| | - Chuen Neng Lee
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore
| | - Xiaoyuan Chen
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore
- Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore
- Department of Chemical and Biomolecular Engineering, and Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117575, Singapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
| | - Jiong-Wei Wang
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore
- Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117609, Singapore
- Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS), 14 Medical Drive, Singapore 117599, Singapore
- Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive, Singapore 117593, Singapore
| | - Huaxi Yi
- College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. China
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100083, China
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17
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Wojtacha P, Trybowski W, Podlasz P, Żmigrodzka M, Tyburski J, Polak-Śliwińska M, Jakimiuk E, Bakuła T, Baranowski M, Żuk-Gołaszewska K, Zielonka Ł, Obremski K. Effects of a Low Dose of T-2 Toxin on the Percentage of T and B Lymphocytes and Cytokine Secretion in the Porcine Ileal Wall. Toxins (Basel) 2021; 13:toxins13040277. [PMID: 33924586 PMCID: PMC8070124 DOI: 10.3390/toxins13040277] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 04/09/2021] [Accepted: 04/11/2021] [Indexed: 12/12/2022] Open
Abstract
Plant materials used in the production of pig feed are frequently contaminated with mycotoxins. T-2 toxin is a secondary metabolite of selected Fusarium species, and it can exert a harmful influence on living organisms. Most mycotoxins enter the body via the gastrointestinal tract, and they can modulate the gut-associated lymphoid tissue (GALT) function. However, little is known about the influence of low T-2 toxin doses on GALT. Therefore, the aim of this study was to evaluate the effect of T-2 toxin administered at 50% of the lowest-observed-adverse-effect level (LOAEL) on the percentage of CD2+ T cells, CD4+ T helper cells, CD8+ cytotoxic T cells, CD4+CD8+ double-positive T cells, TCRγδ+ cells, CD5+CD8- B1 cells, and CD21+ B2 cells, and the secretion of proinflammatory (IFN-γ, IL-1β, IL-2, IL-12/23p40, IL-17A), anti-inflammatory, and regulatory (IL-4, IL-10, TGF-β) cytokines in the porcine ileal wall. The results of the study revealed that T-2 toxin disrupts the development of tolerance to food antigens by enhancing the secretion of proinflammatory and regulatory cytokines and decreasing the production of anti-inflammatory TGF-β. T-2 toxin triggered the cellular response, which was manifested by an increase in the percentage of CD8+ T cells and a decrease in the percentage of B2 and Tγδ lymphocytes.
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Affiliation(s)
- Paweł Wojtacha
- Department of Industrial and Food Microbiology, Faculty of Food Science, University of Warmia and Mazury in Olsztyn, 10-726 Olsztyn, Poland;
| | | | - Piotr Podlasz
- Department of Pathophysiology, Forensic Veterinary Medicine and Administration, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland
- Correspondence: (P.P.); (K.O.)
| | - Magdalena Żmigrodzka
- Department of Pathology and Veterinary Diagnostics, Institute of Veterinary Medicine, Warsaw University of Life Sciences—SGGW, 02-776 Warsaw, Poland;
| | - Józef Tyburski
- Department of Agroecosystems and Horticulture, Faculty of Agriculture and Forestry, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland;
| | - Magdalena Polak-Śliwińska
- Department of Commodity Science and Food Analysis, Faculty of Food Science, University of Warmia and Mazury in Olsztyn, 10-726 Olsztyn, Poland;
| | - Ewa Jakimiuk
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland; (E.J.); (T.B.); (M.B.); (Ł.Z.)
| | - Tadeusz Bakuła
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland; (E.J.); (T.B.); (M.B.); (Ł.Z.)
| | - Mirosław Baranowski
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland; (E.J.); (T.B.); (M.B.); (Ł.Z.)
| | - Krystyna Żuk-Gołaszewska
- Department of Agrotechnology and Agribusines, Faculty of Agriculture and Forestry, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland;
| | - Łukasz Zielonka
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland; (E.J.); (T.B.); (M.B.); (Ł.Z.)
| | - Kazimierz Obremski
- Department of Veterinary Prevention and Feed Hygiene, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-718 Olsztyn, Poland; (E.J.); (T.B.); (M.B.); (Ł.Z.)
- Correspondence: (P.P.); (K.O.)
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18
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Phenolic compounds from jaboticaba (Plinia jaboticaba (Vell.) Berg) ameliorate intestinal inflammation and associated endotoxemia in obesity. Food Res Int 2021; 141:110139. [PMID: 33642006 DOI: 10.1016/j.foodres.2021.110139] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 02/08/2023]
Abstract
Jaboticaba (Plinia jaboticaba (Vell.) Berg) is a Brazilian native fruit belonging to the Myrtaceae family. Previously it was demonstrated that phenolic-rich extracts from jaboticaba (PEJ) possess health-beneficial properties in diet-induced obesity; however, whether PEJ modulates the obesity-associated intestinal inflammatory status remains unclear. Thus, male C57BL/6J obese mice were fed a high-fat-sugar (HFS) diet and received PEJ at two doses, 50 mg gallic acid equivalent (GAE)/kg body weight (BW) (PEJ1 group), and 100 mg GAE/kg BW (PEJ2 group), or water (HFS group) by oral gavage for 14 weeks. PEJ groups presented a reduced body weight gain and adiposity and were protected against insulin resistance and dyslipidemia. In addition, PEJ prevented metabolic endotoxemia linked to an attenuation of the HFS diet-induced intestinal inflammation via down-regulation of pro-inflammatory mediators such as tumor necrosis factor (TNF-α), membrane transporter toll-like receptor-4 (TLR-4) and nuclear factor-κB (NF-κB) in the colon. These anti-inflammatory effects appear to be involved, at least in part, with an inhibition of the colonic inflammasome pathway of obese mice.
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19
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Gastman B, Agarwal PK, Berger A, Boland G, Broderick S, Butterfield LH, Byrd D, Fecci PE, Ferris RL, Fong Y, Goff SL, Grabowski MM, Ito F, Lim M, Lotze MT, Mahdi H, Malafa M, Morris CD, Murthy P, Neves RI, Odunsi A, Pai SI, Prabhakaran S, Rosenberg SA, Saoud R, Sethuraman J, Skitzki J, Slingluff CL, Sondak VK, Sunwoo JB, Turcotte S, Yeung CC, Kaufman HL. Defining best practices for tissue procurement in immuno-oncology clinical trials: consensus statement from the Society for Immunotherapy of Cancer Surgery Committee. J Immunother Cancer 2020; 8:e001583. [PMID: 33199512 PMCID: PMC7670953 DOI: 10.1136/jitc-2020-001583] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2020] [Indexed: 12/11/2022] Open
Abstract
Immunotherapy is now a cornerstone for cancer treatment, and much attention has been placed on the identification of prognostic and predictive biomarkers. The success of biomarker development is dependent on accurate and timely collection of biospecimens and high-quality processing, storage and shipping. Tumors are also increasingly used as source material for the generation of therapeutic T cells. There have been few guidelines or consensus statements on how to optimally collect and manage biospecimens and source material being used for immunotherapy and related research. The Society for Immunotherapy of Cancer Surgery Committee has brought together surgical experts from multiple subspecialty disciplines to identify best practices and to provide consensus on how best to access and manage specific tissues for immuno-oncology treatments and clinical investigation. In addition, the committee recommends early integration of surgeons and other interventional physicians with expertise in biospecimen collection, especially in clinical trials, to optimize the quality of tissue and the validity of correlative clinical studies in cancer immunotherapy.
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Affiliation(s)
- Brian Gastman
- Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio, USA
| | - Piyush K Agarwal
- Department of Surgery, University of Chicago, Chicago, Illinois, USA
| | - Adam Berger
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
| | - Genevieve Boland
- Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Stephen Broderick
- Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
- Department of Surgery, Johns Hopkins Medicine, Baltimore, Maryland, USA
| | - Lisa H Butterfield
- Parker Institute for Cancer Immunotherapy, San Francisco, California, USA
- Microbiology and Immunology, University of California San Francisco, San Francisco, California, USA
| | - David Byrd
- Department of Surgery, University of Washington, Seattle, Washington, USA
| | - Peter E Fecci
- Department of Neurosurgery, Duke University School of Medicine, Durham, North Carolina, USA
| | - Robert L Ferris
- Departments of Otolaryngology, Immunology, and Radiation Oncology, University of Pittsburgh Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
| | - Yuman Fong
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | | | - Matthew M Grabowski
- Department of Neurosurgery, Duke Center for Brain and Spine Metastasis, Durham, North Carolina, USA
| | - Fumito Ito
- Center for Immunotherapy, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Michael Lim
- Departments of Neurosurgery, Oncology, Radiation Oncology, and Otolaryngology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Michael T Lotze
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Haider Mahdi
- OBGYN and Women's Health Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Mokenge Malafa
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida, USA
| | - Carol D Morris
- Division of Orthopaedic Oncology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Pranav Murthy
- Department of Surgery, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Rogerio I Neves
- Department of Surgery, Penn State Cancer Institute, Hershey, Pennsylvania, USA
| | - Adekunle Odunsi
- Departments of Immunology and Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York, USA
| | - Sara I Pai
- Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Sangeetha Prabhakaran
- Division of Surgical Oncology, Department of Surgery, UNM Comprehensive Cancer Center, University of New Mexico, Albuquerque, New Mexico, USA
| | | | - Ragheed Saoud
- Department of Surgery, University of Chicago Hospitals, Chicago, Illinois, United States
| | | | - Joseph Skitzki
- Departments of Surgical Oncology and Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Craig L Slingluff
- Department of Surgery, Division of Surgical Oncology, Breast and Melanoma Surgery, University of Virginia, Charlottesville, Virginia, USA
| | - Vernon K Sondak
- Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida, USA
| | - John B Sunwoo
- Department of Otolaryngology, Stanford University School of Medicine, Stanford, California, USA
| | - Simon Turcotte
- Surgery Department, Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada
| | - Cecilia Cs Yeung
- Department of Pathology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
| | - Howard L Kaufman
- Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Immuneering Corp, Cambridge, Massachusetts, USA
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20
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Emerging role of microbiota in immunomodulation and cancer immunotherapy. Semin Cancer Biol 2020; 70:37-52. [PMID: 32580024 DOI: 10.1016/j.semcancer.2020.06.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 06/11/2020] [Accepted: 06/11/2020] [Indexed: 02/08/2023]
Abstract
Gut microbiota is emerging as a key modulator of the immune system. Alteration of gut microbiota impacts functioning of the immune system and pathophysiology of several diseases, including cancer. Growing evidence indicates that gut microbiota is not only involved in carcinogenesis but also has an impact on the efficacy and toxicity of cancer therapy. Recently, several pre-clinical and clinical studies across diverse cancer types reported the influence of gut microbiota on the host immune response to immunotherapy. Advancement in our understanding of the mechanism behind microbiota-mediated modulation of immune response is paramount for their utilization as cancer therapeutics. These microbial therapies in combination with conventional immunotherapeutic methods have the potential to transform the pre-existing treatment strategies to personalized cancer therapy. In this review, we have summarized the current status of research in the field and discussed the role of microbiota as an immune system modulator in context of cancer and their impact on immunotherapy.
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21
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Segrist E, Cherry S. Using Diverse Model Systems to Define Intestinal Epithelial Defenses to Enteric Viral Infections. Cell Host Microbe 2020; 27:329-344. [PMID: 32164844 DOI: 10.1016/j.chom.2020.02.003] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The intestine is an essential physical and immunological barrier comprised of a monolayer of diverse and specialized epithelial cells that perform functions ranging from nutrient absorption to pathogen sensing and intestinal homeostasis. The intestinal barrier prevents translocation of intestinal microbes into internal compartments. The microbiota is comprised of a complex community largely populated by diverse bacterial species that provide metabolites, nutrients, and immune stimuli that promote intestinal and organismal health. Although commensal organisms promote health, enteric pathogens, including a diverse plethora of enteric viruses, cause acute and chronic diseases. The barrier epithelium plays fundamental roles in immune defenses against enteric viral infections by integrating diverse signals, including those from the microbiota, to prevent disease. Importantly, many model systems have contributed to our understanding of this complex interface. This review will focus on the antiviral mechanisms at play within the intestinal epithelium and how these responses are shaped by the microbiota.
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Affiliation(s)
- Elisha Segrist
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Sara Cherry
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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22
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Polewski MA, Esquivel-Alvarado D, Wedde NS, Kruger CG, Reed JD. Isolation and Characterization of Blueberry Polyphenolic Components and Their Effects on Gut Barrier Dysfunction. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2020; 68:2940-2947. [PMID: 31199652 DOI: 10.1021/acs.jafc.9b01689] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Highbush blueberries contain anthocyanins and proanthocyanidins that have antimicrobial and anti-inflammatory bioactivities. We isolated and characterized three polyphenolic fractions, a total polyphenol fraction (TPF), an anthocyanin-enriched fraction (AEF), and a proanthocyanidin-enriched fraction (PEF), from freeze-dried blueberry powder and evaluated their effects on an in vitro model of gut barrier dysfunction. High-performance liquid chromatography chromatograms illustrate successful fractionation of the blueberry powder into TPF, AEF, and PEF. AEF contained 21 anthocyanins, and PEF contained proanthocyanidin oligomers of (epi)catechin with primarily B-type interflavan bonds. The model uses a strain of Escherichia coli to disrupt a Caco-2 cell monolayer on Transwell inserts. Barrier function was measured by transepithelial electrical resistance (TEER), a marker of membrane permeability. All fractions were able to restore TEER values after an E. coli challenge when compared to the control, while AEF was able to attenuate the E. coli-induced decrease in TEER in a dose-dependent manner.
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Affiliation(s)
- Michael A Polewski
- Reed Research Group, Department of Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, Wisconsin 53706, United States
| | - Daniel Esquivel-Alvarado
- Reed Research Group, Department of Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, Wisconsin 53706, United States
| | - Nicholas S Wedde
- Reed Research Group, Department of Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, Wisconsin 53706, United States
| | - Christian G Kruger
- Reed Research Group, Department of Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, Wisconsin 53706, United States
| | - Jess D Reed
- Reed Research Group, Department of Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, Wisconsin 53706, United States
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23
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Al-Harbi A, Lary S, Edwards MG, Qusti S, Cockburn A, Poulsen M, Gatehouse AMR. A proteomic-based approach to study underlying molecular responses of the small intestine of Wistar rats to genetically modified corn (MON810). Transgenic Res 2019; 28:479-498. [PMID: 31172414 PMCID: PMC6848250 DOI: 10.1007/s11248-019-00157-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 05/27/2019] [Indexed: 12/13/2022]
Abstract
A genetically modified (GM) commercial corn variety, MON810, resistant to European corn borer, has been shown to be non-toxic to mammals in a number of rodent feeding studies carried out in accordance with OECD Guidelines. Insect resistance results from expression of the Cry1Ab gene encoding an insecticidal Bt protein that causes lysis and cell death in susceptible insect larvae by binding to midgut epithelial cells, which is a key determinant of Cry toxin species specificity. Whilst whole animal studies are still recognised as the 'gold standard' for safety assessment, they only provide indirect evidence for changes at the cellular/organ/tissue level. In contrast, omics-based technologies enable mechanistic understanding of toxicological or nutritional events at the cellular/receptor level. To address this important knowledge-gap and to gain insights into the underlying molecular responses in rat to MON810, differential gene expression in the epithelial cells of the small intestine of rats fed formulated diets containing MON810, its near isogenic line, two conventional corn varieties, and a commercial (Purina™) corn-based control diet were investigated using comparative proteomic profiling. Pairwise and five-way comparisons showed that the majority of proteins that were differentially expressed in the small intestine epithelial cells in response to consumption of the different diets in both 7-day and 28-day studies were related to lipid and carbohydrate metabolism and protein biosynthesis. Irrespective of the diet, a limited number of stress-related proteins were shown to be differentially expressed. However these stress-related proteins differed between diets. No adverse clinical or behavioural effects, or biomarkers of adverse health, were observed in rats fed GM corn compared to the other corn diets. These findings suggest that MON810 has negligible effects on the small intestine of rats at the cellular level compared with the well-documented toxicity observed in susceptible insects.
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Affiliation(s)
- Asmaa Al-Harbi
- Biochemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box: 42805, Jeddah, 21551, Kingdom of Saudi Arabia
| | - Sahira Lary
- Biochemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box: 42805, Jeddah, 21551, Kingdom of Saudi Arabia
| | - Martin G Edwards
- School of Natural and Environmental Sciences, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK
| | - Safaa Qusti
- Biochemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box: 42805, Jeddah, 21551, Kingdom of Saudi Arabia
| | - Andrew Cockburn
- School of Natural and Environmental Sciences, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK
| | - Morten Poulsen
- The National Food Institute, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark
| | - Angharad M R Gatehouse
- School of Natural and Environmental Sciences, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK.
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24
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Thoo L, Noti M, Krebs P. Keep calm: the intestinal barrier at the interface of peace and war. Cell Death Dis 2019; 10:849. [PMID: 31699962 PMCID: PMC6838056 DOI: 10.1038/s41419-019-2086-z] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Revised: 10/11/2019] [Accepted: 10/23/2019] [Indexed: 12/19/2022]
Abstract
Epithelial barriers have to constantly cope with both harmless and harmful stimuli. The epithelial barrier therefore serves as a dynamic and not static wall to safeguard its proper physiological function while ensuring protection. This is achieved through multiple defence mechanisms involving various cell types - epithelial and non-epithelial - that work in an integrated manner to build protective barriers at mucosal sites. Damage may nevertheless occur, due to pathogens, physical insults or dysregulated immune responses, which trigger a physiologic acute or a pathologic chronic inflammatory cascade. Inflammation is often viewed as a pathological condition, particularly due to the increasing prevalence of chronic inflammatory (intestinal) diseases. However, inflammation is also necessary for wound healing. The aetiology of chronic inflammatory diseases is incompletely understood and identification of the underlying mechanisms would reveal additional therapeutic approaches. Resolution is an active host response to end ongoing inflammation but its relevance is under-appreciated. Currently, most therapies aim at dampening inflammation at damaged mucosal sites, yet these approaches do not efficiently shut down the inflammation process nor repair the epithelial barrier. Therefore, future treatment strategies should also promote the resolution phase. Yet, the task of repairing the barrier can be an arduous endeavour considering its multiple integrated layers of defence - which is advantageous for damage prevention but becomes challenging to repair at multiple levels. In this review, using the intestines as a model epithelial organ and barrier paradigm, we describe the consequences of chronic inflammation and highlight the importance of the mucosae to engage resolving processes to restore epithelial barrier integrity and function. We further discuss the contribution of pre-mRNA alternative splicing to barrier integrity and intestinal homeostasis. Following discussions on current open questions and challenges, we propose a model in which resolution of inflammation represents a key mechanism for the restoration of epithelial integrity and function.
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Affiliation(s)
- Lester Thoo
- Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.,Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
| | - Mario Noti
- Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.,Department of Gastro-Intestinal Health, Immunology, Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
| | - Philippe Krebs
- Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
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25
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Tulyeu J, Kumagai H, Jimbo E, Watanabe S, Yokoyama K, Cui L, Osaka H, Mieno M, Yamagata T. Probiotics Prevents Sensitization to Oral Antigen and Subsequent Increases in Intestinal Tight Junction Permeability in Juvenile-Young Adult Rats. Microorganisms 2019; 7:microorganisms7100463. [PMID: 31623229 PMCID: PMC6843414 DOI: 10.3390/microorganisms7100463] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/10/2019] [Accepted: 10/14/2019] [Indexed: 12/16/2022] Open
Abstract
Increased intestinal permeability is thought to underlie the pathogenesis of food allergy. We explore the mechanism responsible for changes in the morphology and function of the intestinal barrier using a rat model of food allergy, focusing on the contribution of intestinal microbiota. Juvenile–young adult rats were sensitized with ovalbumin and treated with antibiotics or probiotics (Clostridium butyricum and Lactobacillus reuteri), respectively. The serum ovalbumin-IgE levels, intestinal permeability, histopathological features, tight junction (TJ)-associated proteins, Th2 cytokines, and gut microbiota in feces were analyzed in each group. Sensitized rats showed an increase in ovalbumin-IgE levels and intestinal permeability with gut mucosal inflammation, whereas rats that received probiotics were only mildly affected. Rats given ovalbumin, but not those given probiotics, showed a reduction in both TJ-related protein expression and localization. Th2 cytokine levels were increased in the sensitized rats, but not in those given probiotics. TJs in rats treated with ovalbumin and antibiotics were disrupted, but those in rats administered probiotics were undamaged. Clostridiaceae were increased in the probiotics groups, especially Alkaliphilus, relative to the ovalbumin-sensitized group. Gut microbiota appears to play a role in regulating epithelial barrier function, and probiotics may help to prevent food sensitization through the up-regulation of TJ proteins.
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Affiliation(s)
- Janyerkye Tulyeu
- Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan.
- Department of Immunology and Laboratory, School of Biomedicine, Mongolian National University of Medical Sciences, Jamyan St 3, Ulaanbaatar 14210, Mongolia.
| | - Hideki Kumagai
- Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan.
| | - Eriko Jimbo
- Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan.
| | - Shinya Watanabe
- Division of Bacteriology, Department of Infection and Immunity, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 3290498, Japan.
| | - Koji Yokoyama
- Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan.
| | - Longzhu Cui
- Division of Bacteriology, Department of Infection and Immunity, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 3290498, Japan.
| | - Hitoshi Osaka
- Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan.
| | - Makiko Mieno
- Department of Medical Informatics, Center for Information, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan.
| | - Takanori Yamagata
- Department of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan.
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26
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Lysophosphatidic Acid and Autotaxin-associated Effects on the Initiation and Progression of Colorectal Cancer. Cancers (Basel) 2019; 11:cancers11070958. [PMID: 31323936 PMCID: PMC6678549 DOI: 10.3390/cancers11070958] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 07/04/2019] [Accepted: 07/08/2019] [Indexed: 02/07/2023] Open
Abstract
The intestinal epithelium interacts dynamically with the immune system to maintain its barrier function to protect the host, while performing the physiological roles in absorption of nutrients, electrolytes, water and minerals. The importance of lysophosphatidic acid (LPA) and its receptors in the gut has been progressively appreciated. LPA signaling modulates cell proliferation, invasion, adhesion, angiogenesis, and survival that can promote cancer growth and metastasis. These effects are equally important for the maintenance of the epithelial barrier in the gut, which forms the first line of defense against the milieu of potentially pathogenic stimuli. This review focuses on the LPA-mediated signaling that potentially contributes to inflammation and tumor formation in the gastrointestinal tract.
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27
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T Cell Recruitment to the Intestinal Stem Cell Compartment Drives Immune-Mediated Intestinal Damage after Allogeneic Transplantation. Immunity 2019; 51:90-103.e3. [PMID: 31278057 DOI: 10.1016/j.immuni.2019.06.003] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 04/01/2019] [Accepted: 06/05/2019] [Indexed: 12/30/2022]
Abstract
The key sites within the gastrointestinal (GI) tract where T cells mediate effector responses and the impact of these responses on intestinal stem cells (ISCs) remain unclear. Using experimental bone marrow transplantation to model immune-mediated GI damage and 3D imaging to analyze T cell localization, we found that the ISC compartment is the primary intestinal site targeted by T cells after transplantation. Recruitment to the crypt base region resulted in direct T cell engagement with the stem cell compartment and loss of crypt base columnar ISCs, which expressed both MHC classes I and II. Vasculature expressing the adhesion molecule MAdCAM-1 clustered near the crypt base, preferentially regulating crypt compartment invasion and ISC reduction without affecting T cell migration to villi. These findings indicate that allogeneic T cells rapidly access the stem cell niche after transplantation, and this targeted recruitment to the stem cell compartment results in ISC loss during immune-mediated GI damage.
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28
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Abstract
The gut-associated lymphoid tissue (GALT) faces a considerable challenge. It encounters antigens derived from an estimated 1014 commensal microbes and greater than 30 kg of food proteins yearly. It must distinguish these harmless antigens from potential pathogens and mount the appropriate host immune response. Local and systemic hyporesponsiveness to dietary antigens, classically referred to as oral tolerance, comprises a distinct complement of adaptive cellular and humoral immune responses. It is increasingly evident that a functional epithelial barrier engaged in intimate interplay with innate immune cells and the resident microbiota is critical to establishing and maintaining oral tolerance. Moreover, innate immune cells serve as a bridge between the microbiota, epithelium, and the adaptive immune system, parlaying tonic microbial stimulation into signals critical for mucosal homeostasis. Dysregulation of gut homeostasis and the subsequent disruption of tolerance therefore have clinically significant consequences for the development of food allergy.
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Affiliation(s)
- Onyinye I Iweala
- UNC Food Allergy Initiative and Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, The University of North Carolina at Chapel Hill, North Carolina 27599-7280, USA;
| | - Cathryn R Nagler
- Department of Pathology, Biological Sciences Division, University of Chicago, Chicago, Illinois 60637-1824, USA;
- Committee on Immunology, Biological Sciences Division, University of Chicago, Chicago, Illinois 60637-1824, USA
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29
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Colostrum Antibodies, Egg Antibodies and Monoclonal Antibodies Providing Passive Immunity for Animals. NUTRACEUTICALS IN VETERINARY MEDICINE 2019. [PMCID: PMC7123268 DOI: 10.1007/978-3-030-04624-8_18] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Passive immunity can be provided to animals by several sources of antibodies including from colostrum, avian eggs, and monoclonal sources. These antibodies have been shown protect production and companion animals from a number of pathogens. This chapter reviews the immune system for the principles of immune response to antigens and the synthesis of immunoglobulins of the five classes of antibodies in the body. Colostrum antibodies are described for passive immunity protection in animals such as calves. Chicken egg antibodies are another source of antibodies for passive immunity. Therapeutic monoclonal antibodies are also used to provide passive immunity in the veterinary field.
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30
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Fu J, Li G, Wu J, Wang Z. Intestinal IgA positive lymphocytes in acute liver necrosis decrease due to lymphocyte homing disturbance and apoptosis. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 111:101-105. [PMID: 30318894 DOI: 10.17235/reed.2018.5656/2018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
AIM the number of intestinal IgA+ lymphocytes are decreased in acute liver necrosis and the mechanism remains poorly understood. The purpose of this study was to observe the role of lymphocyte homing and apoptosis associated with decreased intestinal IgA positive lymphocytes in acute liver necrosis. METHODS the acute liver necrosis mouse model and LTβR pre-treatment were used to assess intestinal mucosal addressin cell adhesion molecule-1 (MAdCAM - 1) expression, cell apoptosis, IgA+ cells and secretory immunoglobulin A (SIgA). RESULTS MAdCAM - 1 mRNA and protein expression decreased significantly in the acute necrosis group; 0.57 ± 0.032 fold vs. baseline (p < 0.05) and 0.45 ± 0.072 fold vs. baseline (p < 0.05), respectively. LTβR pre-treatment could significantly improve the decline of MAdCAM - 1 mRNA and protein expression in the intestinal mucosa (1.83 ± 0.064 fold vs. baseline, p < 0.05 and 1.75 ± 0.046 fold vs. baseline, p < 0.05, respectively) and partially restore the decline in IgA+ lymphocytes and SIgA levels. There were increased rates of enterocyte apoptosis in both the acute liver necrosis and LTβR pre-treatment group; 0.79% vs. control (p < 0.05) and 0.77% vs. control (p < 0.05), respectively). CONCLUSION our results suggest that the dysfunction of lymphocyte homing and apoptosis are both involved with decreased intestinal IgA+ lymphocytes in acute liver necrosis. LTβR pre-treatment can partially restore IgA+ cells and SIgA by increasing MAdCAM - 1 expression, rather than inhibiting lymphocyte apoptosis.
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Affiliation(s)
- Jinlong Fu
- Gastroenterology, The Affiliated Hospital，Hangzhou Normal University, China
| | - Guodong Li
- Gastroenterology, The Affiliated Hospital，Hangzhou Normal University School of Medicine
| | - Jianliang Wu
- Gastroenterology, The Affiliated Hospital，Hangzhou Normal University School of Medicine, China
| | - Zhiyong Wang
- Gastroenterology, The Affiliated Hospital，Hangzhou Normal University School of Medicine, China
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31
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Song C, Liu B, Xu P, Xie J, Ge X, Zhou Q, Sun C, Zhang H, Shan F, Yang Z. Oxidized fish oil injury stress in Megalobrama amblycephala: Evaluated by growth, intestinal physiology, and transcriptome-based PI3K-Akt/NF-κB/TCR inflammatory signaling. FISH & SHELLFISH IMMUNOLOGY 2018; 81:446-455. [PMID: 30064020 DOI: 10.1016/j.fsi.2018.07.049] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 07/22/2018] [Accepted: 07/27/2018] [Indexed: 06/08/2023]
Abstract
Lipids are essential nutrients for animal. Oxidized lipid might induce injury stress for fish. Here we conducted a 12-week rearing experiment with diets containing 0, 2, 4, and 6% oxidized fish oil (6F, 4F2OF, 2F4OF, and 6OF) to describe the oxidative impairment mechanism on teleost fish blunt snout bream, Megalobrama amblycephala. Results were evaluated by growth performance, intestinal physiology, and transcriptome-based PI3K-Akt/NF-κB/TCR inflammatory signaling. From the results, 6OF reduced growth performance with increased FCR and reduced FBW, WGR and SGR compare with 6 F. Meanwhile, oxidized fish oil treatments also increased antioxidant enzyme activity, suggesting an impaired physiological condition. The plasmatic antioxidant enzyme activity of T-SOD, GSH-Px, ASAFR, concentration of MDA and cortisol were significantly increased in 6OF, while GSH concentration was decreased. Histological ultrastructure revealed the integrity of mid-intestinal cells and villus were destroyed in 6OF. Moreover, transcriptomic analysis revealed PI3K-Akt/NF-κB/TCR inflammatory signaling were active to oxidized fish oil stress. We verified the expression of twelve key genes related to this signaling by RT-PCR, which revealed TLR2, PI3K, Akt, NF-κB, MHCII-β, TCR-α, TGF-β, TNF-α, IL-6, IL-1β, GPx1 and GSTm were all activated under 6OF stimulation. We found that oxidized fish oil may induce oxidative stress, destroy intestinal integrity, produce free radical, dysregulate lipid metabolism and oxidative balance, reversely affect the physiological adaptation, and eventually lead to growth inhibition. This study revealed the mechanism of PI3K-Akt/NF-κB/TCR inflammatory signaling in M. amblycephala under oxidized fish oil stress, which may help to understand the complex regulation involved in lipid oxidative stress resistance.
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Affiliation(s)
- Changyou Song
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China.
| | - Bo Liu
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China.
| | - Pao Xu
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China.
| | - Jun Xie
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China
| | - Xianping Ge
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China
| | - Qunlan Zhou
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China
| | - Cunxin Sun
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, China
| | - Huimin Zhang
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, 214081, China
| | - Fan Shan
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, 214081, China
| | - Zhenfei Yang
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi, 214081, China
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Hajavi J, Esmaeili SA, Varasteh AR, Vazini H, Atabati H, Mardani F, Momtazi-Borojeni AA, Hashemi M, Sankian M, Sahebkar A. The immunomodulatory role of probiotics in allergy therapy. J Cell Physiol 2018; 234:2386-2398. [PMID: 30192002 DOI: 10.1002/jcp.27263] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 07/24/2018] [Indexed: 12/14/2022]
Abstract
The increased incidence of allergic disorders may be the result of a relative fall in microbial induction in the intestinal immune system during infancy and early childhood. Probiotics have recently been proposed as viable microorganisms for the prevention and treatment of specific allergic diseases. Different mechanisms have been considered for this probiotic property, such as generation of cytokines from activated pro-T-helper type 1 after bacterial contact. However, the effects of its immunomodulatory potential require validation for clinical applications. This review will focus on the currently available data on the benefits of probiotics in allergy disease.
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Affiliation(s)
- Jafar Hajavi
- Department of Basic Sciences, Faculty of Allied Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Seyed-Alireza Esmaeili
- Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abdol-Reza Varasteh
- Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Vazini
- Nursing Department, Basic Sciences Faculty, Hamedan Branch, Islamic Azad University, Hamedan, Iran
| | - Hadi Atabati
- Leishmaniasis Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Fatemeh Mardani
- Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir A Momtazi-Borojeni
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Biotechnology, Nanotechnology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Hashemi
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mojtaba Sankian
- Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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The latest FAD - Faecal antibody detection in cattle. Protocol and results from three UK beef farms naturally infected with gastrointestinal nematodes. Parasitology 2018; 146:89-96. [PMID: 30086804 PMCID: PMC6230468 DOI: 10.1017/s0031182018000902] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Antibodies at gastrointestinal mucosal membranes play a vital role in immunological protection against a range of pathogens, including helminths. Gastrointestinal health is central to efficient livestock production, and such infections cause significant losses. Fecal samples were taken from 114 cattle, across three beef farms, with matched blood samples taken from 22 of those animals. To achieve fecal antibody detection, a novel fecal supernatant was extracted. Fecal supernatant and serum samples were then analysed, using adapted enzyme-linked immunosorbent assay protocols, for levels of total immunoglobulin (Ig)A, IgG, IgM, and Teladorsagia circumcincta-specific IgA, IgG, IgM and IgE (in the absence of reagents for cattle-specific nematode species). Fecal nematode egg counts were conducted on all fecal samples. Assays performed successfully and showed that IgA was the predominant antibody in fecal samples, whereas IgG was predominant in serum. Total IgA in feces and serum correlated within individuals (0.581, P = 0.005), but other Ig types did not. Results support the hypothesis that the tested protocols are an effective method for the non-invasive assessment of cattle immunology. The method could be used as part of animal health assessments, although further work is required to interpret the relationship between results and levels of infection and immunity.
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Ji Y, Li X, Zhu Y, Li N, Zhang N, Niu M. Faecal microRNA as a biomarker of the activity and prognosis of inflammatory bowel diseases. Biochem Biophys Res Commun 2018; 503:2443-2450. [PMID: 29969632 DOI: 10.1016/j.bbrc.2018.06.174] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 06/30/2018] [Indexed: 12/29/2022]
Abstract
Reasons underlying the individual differences in the clinical manifestations of inflammatory bowel diseases (IBD) and the mechanism by which the host screens the intestinal microbiota remain unclear. The presence of miRNA in faeces might be a potential clue into differences in gut microbiota among these patients. In this study, we analysed the differences in miRNA levels in faecal samples from 117 patients diagnosed with IBD. There was a significant difference in faecal miRNAs between healthy subjects and those with inactive IBD. Further analysis showed that some miRNAs might indicate the severity of IBD activity and prognosis. Sequencing analysis of the 16S RNA V4 region in faecal microbiota in these IBD patients revealed significant differences in the phylogenetic architecture between subjects with active or inactive IBD and between IBD patients and healthy subjects. Finally, in vitro studies showed that these differentially expressed miRNAs have different effects on the proliferative activity of the intestinal microorganisms Fusobacterium nucleatum (Fn), Escherichia coli (E. coli) and segmental filamentous bacteria (SFB). We observed the dynamic uptake of miRNA by these bacteria using flow cytometry. This study reveals a potential link between faecal miRNA, intestinal microbiota, IBD activity and prognosis.
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Affiliation(s)
- Yahong Ji
- Department of Gastroenterology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Xiaoli Li
- Department of Gastroenterology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Ying Zhu
- Department of Gastroenterology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Na Li
- Department of Gastroenterology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Nana Zhang
- Department of Gastroenterology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China
| | - Min Niu
- Department of Gastroenterology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
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Landa SB, Korabliov PV, Semenova EV, Filatov MV. Peculiarities of the formation and subsequent removal of the circulating immune complexes from the bloodstream during the process of digestion. F1000Res 2018; 7:618. [PMID: 30079242 PMCID: PMC6058468 DOI: 10.12688/f1000research.14406.1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/10/2018] [Indexed: 12/24/2022] Open
Abstract
Background: Large protein aggregates, known as circulating immune complexes (CICs), are formed in biological fluids as a result of the development of the body's immune response to various provoking factors. The kinetic characteristics of the formation and removal of immune complexes (ICs), their physical parameters, the isotypic composition of immunoglobulins (Igs) and the antigenic component of the CICs may reflect certain aspects of certain pathological and metabolic processes taking place in humans and animals. The aim of this study is to assess the kinetic characteristics of the formation and removal of the CICs that form in blood after eating. We also analyze the changes in the isotypic composition of Igs of ICs that accompany this biological process in rodents and humans. Methods: We identified the CICs, which differed in size and class of Igs, using dynamic light scattering. To remove ICs from the plasma, we used immune-affinity sedimentation. Monoclonal antibodies for the Igs of different isotypes were added to the plasma samples to determine the isotypic composition of the ICs. Results: A large number of ICs were formed in the blood of rats and humans after eating (food CICs). In rats, food ICs are almost immediately filtered in the liver, without circulating in the bloodstream through the body. In humans, the level of food ICs in the blood increases for 3.5 h after ingestion, then within 7-8 h their gradual removal takes place. It was found that in the process of digestion in humans, the isotypic composition of Igs in the CICs changes and becomes more diverse. Conclusions: The molecular-cellular mechanisms of the formation and utilization of food CICs in humans and rodents do not match completely.
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Affiliation(s)
- Sergej B. Landa
- Division of Molecular and Radiation Biophysics, National Research Center , Gatchina, 188300, Russian Federation
| | - Pavel V. Korabliov
- State Research Institute Center for Innovative Medicine, Vilnius, LT-01102, Lithuania
| | - Elena V. Semenova
- Division of Molecular and Radiation Biophysics, National Research Center , Gatchina, 188300, Russian Federation
| | - Michael V. Filatov
- Division of Molecular and Radiation Biophysics, National Research Center , Gatchina, 188300, Russian Federation
- Saint Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation, Saint Petersburg, 191036, Russian Federation
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Dou J, Bennett MR. Synthetic Biology and the Gut Microbiome. Biotechnol J 2018; 13:e1700159. [PMID: 28976641 PMCID: PMC5882594 DOI: 10.1002/biot.201700159] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Revised: 08/23/2017] [Indexed: 12/19/2022]
Abstract
The gut microbiome plays a crucial role in maintaining human health. Functions performed by gastrointestinal microbes range from regulating metabolism to modulating immune and nervous system development. Scientists have attempted to exploit this importance through the development of engineered probiotics that are capable of producing and delivering small molecule therapeutics within the gut. However, existing synthetic probiotics are simplistic and fail to replicate the complexity and adaptability of native homeostatic mechanisms. In this review, the ways in which the tools and approaches of synthetic biology have been applied to improve the efficacy of therapeutic probiotics, and the ways in which they might be applied in the future is discussed. Simple devices, such as a bistable switches and integrase memory arrays, have been successfully implemented in the mammalian gut, and models for targeted delivery in this environment have also been developed. In the future, it will be necessary to introduce concepts such as logic-gating and biocontainment mechanisms into synthetic probiotics, as well as to expand the collection of relevant biosensors. Ideally, this will bring us closer to a reality in which engineered therapeutic microbes will be able to accurately diagnose and effectively respond to a variety of disease states.
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Affiliation(s)
- Jennifer Dou
- Department of Biosciences, Rice University, Houston, TX 77005
| | - Matthew R. Bennett
- Department of Biosciences, Rice University, Houston, TX 77005
- Department of Bioengineering, Rice University, Houston, TX 77005
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37
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Hajipour H, Nejabati HR, Latifi Z, Hamdi K, Bahrami-asl Z, Fattahi A, Nouri M. Lymphocytes immunotherapy for preserving pregnancy: Mechanisms and Challenges. Am J Reprod Immunol 2018; 80:e12853. [DOI: 10.1111/aji.12853] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 03/08/2018] [Indexed: 12/31/2022] Open
Affiliation(s)
- Hamed Hajipour
- Department of Reproductive Biology; Faculty of Advanced Medical Sciences; Tabriz University of Medical Sciences; Tabriz Iran
| | - Hamid Reza Nejabati
- Department of Biochemistry and Clinical Laboratories; Faculty of Medicine; Tabriz University of Medical Sciences; Tabriz Iran
| | - Zeinab Latifi
- Department of Biochemistry and Clinical Laboratories; Faculty of Medicine; Tabriz University of Medical Sciences; Tabriz Iran
| | - Kobra Hamdi
- Women's Reproductive Health Research Center; Tabriz University of Medical Sciences; Tabriz Iran
| | - Zahra Bahrami-asl
- Department of Reproductive Biology; Faculty of Advanced Medical Sciences; Tabriz University of Medical Sciences; Tabriz Iran
| | - Amir Fattahi
- Department of Biochemistry and Clinical Laboratories; Faculty of Medicine; Tabriz University of Medical Sciences; Tabriz Iran
- Women's Reproductive Health Research Center; Tabriz University of Medical Sciences; Tabriz Iran
| | - Mohammad Nouri
- Women's Reproductive Health Research Center; Tabriz University of Medical Sciences; Tabriz Iran
- Stem Cell and Regenerative Medicine Institute; Tabriz University of Medical Sciences; Tabriz Iran
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38
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Bortoluzzi C, Rochell SJ, Applegate TJ. Threonine, arginine, and glutamine: Influences on intestinal physiology, immunology, and microbiology in broilers. Poult Sci 2018; 97:937-945. [DOI: 10.3382/ps/pex394] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 11/17/2017] [Indexed: 12/26/2022] Open
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39
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Indrio F, Riezzo G, Tafuri S, Ficarella M, Carlucci B, Bisceglia M, Polimeno L, Francavilla R. Probiotic Supplementation in Preterm: Feeding Intolerance and Hospital Cost. Nutrients 2017; 9:nu9090965. [PMID: 28858247 PMCID: PMC5622725 DOI: 10.3390/nu9090965] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 08/25/2017] [Accepted: 08/28/2017] [Indexed: 12/21/2022] Open
Abstract
We hypothesized that giving the probiotic strain Lactobacillus reuteri (L. reuteri) DSM 17938 to preterm, formula-fed infants would prevent an early traumatic intestinal inflammatory insult modulating intestinal cytokine profile and reducing the onset of feeding intolerance. Newborn were randomly allocated during the first 48 h of life to receive either daily probiotic (108 colony forming units (CFUs) of L. reuteri DSM 17938) or placebo for one month. All the newborns underwent to gastric ultrasound for the measurement of gastric emptying time. Fecal samples were collected for the evaluation of fecal cytokines. Clinical data on feeding intolerance and weight gain were collected. The costs of hospital stays were calculated. The results showed that the newborns receiving L. reuteri DSM 17938 had a significant decrease in the number of days needed to reach full enteral feeding (p < 0.01), days of hospital stay (p < 0.01), and days of antibiotic treatment (p < 0.01). Statistically significant differences were observed in pattern of fecal cytokine profiles. The anti-inflammatory cytokine interleukin (IL)-10, was increased in newborns receiving L. reuteri DSM 17938. Pro-inflammatory cytokines: IL-17, IL-8, and tumor necrosis factor (TNF)-alpha levels were increased in newborns given placebo. Differences in the gastric emptying and fasting antral area (FAA) were also observed. Our study demonstrates an effective role for L. reuteri DSM 17938 supplementation in preventing feeding intolerance and improving gut motor and immune function development in bottle-fed stable preterm newborns. Another benefit from the use of probiotics is the reducing cost for the Health Care service.
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Affiliation(s)
- Flavia Indrio
- Department of Pediatric, Aldo Moro University of Bari, Ospedale Pediatrico Giovanni XXIII via Amendola 276, 70125 Bari, Italy.
| | - Giuseppe Riezzo
- Laboratory of Nutritional Physiopathology, National Institute for Digestive Diseases, Istituto di Ricerca e Cura a Carattere Scientifico (I.R.C.C.S.), Saverio de Bellis, 70013 Castellana Grotte (BA), Italy.
| | - Silvio Tafuri
- Department of Biomedical Sciences and Human Oncology, Section of Hygiene, Aldo Moro University of Bari, 70125 Bari, Italy.
| | - Maria Ficarella
- Department of Pediatric, Aldo Moro University of Bari, Ospedale Pediatrico Giovanni XXIII via Amendola 276, 70125 Bari, Italy.
| | - Barbara Carlucci
- Division of Neonatology, Ospedale Perrino, 72100 Brindisi, Italy.
| | - Massimo Bisceglia
- Department of Pediatrics, Neonatology Division San Giovanni di Dio Hospital, 88900 Crotone, Italy.
| | - Lorenzo Polimeno
- Department of Organ Transplantation, Gastroenterology Section, University Aldo Moro Bari, 70125 Bari, Italy.
| | - Ruggiero Francavilla
- Department of Pediatric, Aldo Moro University of Bari, Ospedale Pediatrico Giovanni XXIII via Amendola 276, 70125 Bari, Italy.
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40
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Neudecker V, Haneklaus M, Jensen O, Khailova L, Masterson JC, Tye H, Biette K, Jedlicka P, Brodsky KS, Gerich ME, Mack M, Robertson AAB, Cooper MA, Furuta GT, Dinarello CA, O'Neill LA, Eltzschig HK, Masters SL, McNamee EN. Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome. J Exp Med 2017; 214:1737-1752. [PMID: 28487310 PMCID: PMC5460990 DOI: 10.1084/jem.20160462] [Citation(s) in RCA: 283] [Impact Index Per Article: 35.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 01/22/2017] [Accepted: 03/28/2017] [Indexed: 12/16/2022] Open
Abstract
Neudecker et al. define a role for a microRNA, miR-223, in regulating the inflammatory tone of the intestine by constraining nlrp3 inflammasome activation in CCR2+ monocytes and attenuating excessive IL-1β–driven inflammation. Therapeutic nanoparticle delivery of miR-223 mimetics limits experimental colitis. MicroRNA (miRNA)-mediated RNA interference regulates many immune processes, but how miRNA circuits orchestrate aberrant intestinal inflammation during inflammatory bowel disease (IBD) is poorly defined. Here, we report that miR-223 limits intestinal inflammation by constraining the nlrp3 inflammasome. miR-223 was increased in intestinal biopsies from patients with active IBD and in preclinical models of intestinal inflammation. miR-223-/y mice presented with exacerbated myeloid-driven experimental colitis with heightened clinical, histopathological, and cytokine readouts. Mechanistically, enhanced NLRP3 inflammasome expression with elevated IL-1β was a predominant feature during the initiation of colitis with miR-223 deficiency. Depletion of CCR2+ inflammatory monocytes and pharmacologic blockade of IL-1β or NLRP3 abrogated this phenotype. Generation of a novel mouse line, with deletion of the miR-223 binding site in the NLRP3 3′ untranslated region, phenocopied the characteristics of miR-223-/y mice. Finally, nanoparticle-mediated overexpression of miR-223 attenuated experimental colitis, NLRP3 levels, and IL-1β release. Collectively, our data reveal a previously unappreciated role for miR-223 in regulating the innate immune response during intestinal inflammation.
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Affiliation(s)
- Viola Neudecker
- Clinic for Anesthesiology, University Hospital of Ludwig-Maximilians-University, 80539 Munich, Germany.,Department of Anesthesiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Moritz Haneklaus
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
| | - Owen Jensen
- Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045.,Department of Anesthesiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Ludmila Khailova
- Department of Anesthesiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Joanne C Masterson
- Gastrointestinal Eosinophilic Disease Program, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Colorado, Aurora, CO 80045.,Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Hazel Tye
- Division of Inflammation, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia
| | - Kathryn Biette
- Gastrointestinal Eosinophilic Disease Program, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Colorado, Aurora, CO 80045.,Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Paul Jedlicka
- Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Kelley S Brodsky
- Department of Anesthesiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Mark E Gerich
- Division of Gastroenterology and Hepatology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045.,Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Matthias Mack
- Department of Internal Medicine II, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Avril A B Robertson
- Institute for Molecular Bioscience, The University of Queensland, Brisbane City, QLD 4067, Australia
| | - Matthew A Cooper
- Institute for Molecular Bioscience, The University of Queensland, Brisbane City, QLD 4067, Australia
| | - Glenn T Furuta
- Gastrointestinal Eosinophilic Disease Program, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Colorado, Aurora, CO 80045.,Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Charles A Dinarello
- Department of Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.,Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Luke A O'Neill
- School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
| | - Holger K Eltzschig
- Department of Anesthesiology, University of Texas Medical School at Houston, Houston, TX 77030.,Department of Anesthesiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
| | - Seth L Masters
- Division of Inflammation, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.,Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia
| | - Eóin N McNamee
- Mucosal Inflammation Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045 .,Department of Anesthesiology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045
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Haines RA, Urbiztondo RA, Haynes RAH, Simpson E, Niewiesk S, Lairmore MD. Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model. ILAR J 2017; 57:34-43. [PMID: 27034393 DOI: 10.1093/ilar/ilw004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Rabbits have served as a valuable animal model for the pathogenesis of various human diseases, including those related to agents that gain entry through the gastrointestinal tract such as human T cell leukemia virus type 1. However, limited information is available regarding the spatial distribution and phenotypic characterization of major rabbit leukocyte populations in mucosa-associated lymphoid tissues. Herein, we describe the spatial distribution and phenotypic characterization of leukocytes from gut-associated lymphoid tissues (GALT) from 12-week-old New Zealand White rabbits. Our data indicate that rabbits have similar distribution of leukocyte subsets as humans, both in the GALT inductive and effector sites and in mesenteric lymph nodes, spleen, and peripheral blood. GALT inductive sites, including appendix, cecal tonsil, Peyer's patches, and ileocecal plaque, had variable B cell/T cell ratios (ranging from 4.0 to 0.8) with a predominance of CD4 T cells within the T cell population in all four tissues. Intraepithelial and lamina propria compartments contained mostly T cells, with CD4 T cells predominating in the lamina propria compartment and CD8 T cells predominating in the intraepithelial compartment. Mesenteric lymph node, peripheral blood, and splenic samples contained approximately equal percentages of B cells and T cells, with a high proportion of CD4 T cells compared with CD8 T cells. Collectively, our data indicate that New Zealand White rabbits are comparable with humans throughout their GALT and support future studies that use the rabbit model to study human gut-associated disease or infectious agents that gain entry by the oral route.
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Affiliation(s)
- Robyn A Haines
- Robyn A. Haines, DVM, was a PhD student; Rebeccah A. Urbiztondo, DVM, was a Master's student; Rashade A. H. Haynes, PhD, was a postdoctoral fellow; and Elaine Simpson, DVM, was a summer research student in the Department of Veterinary Biosciences at The Ohio State University in Columbus, Ohio. Stefan Niewiesk, PhD, DVM, is professor in the Department of Veterinary Biosciences at The Ohio State University is Columbus, Ohio. Michael D. Lairmore, DVM, PhD, is dean, in the School of Veterinary Medicine at the University of California, Davis in Davis, California
| | - Rebeccah A Urbiztondo
- Robyn A. Haines, DVM, was a PhD student; Rebeccah A. Urbiztondo, DVM, was a Master's student; Rashade A. H. Haynes, PhD, was a postdoctoral fellow; and Elaine Simpson, DVM, was a summer research student in the Department of Veterinary Biosciences at The Ohio State University in Columbus, Ohio. Stefan Niewiesk, PhD, DVM, is professor in the Department of Veterinary Biosciences at The Ohio State University is Columbus, Ohio. Michael D. Lairmore, DVM, PhD, is dean, in the School of Veterinary Medicine at the University of California, Davis in Davis, California
| | - Rashade A H Haynes
- Robyn A. Haines, DVM, was a PhD student; Rebeccah A. Urbiztondo, DVM, was a Master's student; Rashade A. H. Haynes, PhD, was a postdoctoral fellow; and Elaine Simpson, DVM, was a summer research student in the Department of Veterinary Biosciences at The Ohio State University in Columbus, Ohio. Stefan Niewiesk, PhD, DVM, is professor in the Department of Veterinary Biosciences at The Ohio State University is Columbus, Ohio. Michael D. Lairmore, DVM, PhD, is dean, in the School of Veterinary Medicine at the University of California, Davis in Davis, California
| | - Elaine Simpson
- Robyn A. Haines, DVM, was a PhD student; Rebeccah A. Urbiztondo, DVM, was a Master's student; Rashade A. H. Haynes, PhD, was a postdoctoral fellow; and Elaine Simpson, DVM, was a summer research student in the Department of Veterinary Biosciences at The Ohio State University in Columbus, Ohio. Stefan Niewiesk, PhD, DVM, is professor in the Department of Veterinary Biosciences at The Ohio State University is Columbus, Ohio. Michael D. Lairmore, DVM, PhD, is dean, in the School of Veterinary Medicine at the University of California, Davis in Davis, California
| | - Stefan Niewiesk
- Robyn A. Haines, DVM, was a PhD student; Rebeccah A. Urbiztondo, DVM, was a Master's student; Rashade A. H. Haynes, PhD, was a postdoctoral fellow; and Elaine Simpson, DVM, was a summer research student in the Department of Veterinary Biosciences at The Ohio State University in Columbus, Ohio. Stefan Niewiesk, PhD, DVM, is professor in the Department of Veterinary Biosciences at The Ohio State University is Columbus, Ohio. Michael D. Lairmore, DVM, PhD, is dean, in the School of Veterinary Medicine at the University of California, Davis in Davis, California
| | - Michael D Lairmore
- Robyn A. Haines, DVM, was a PhD student; Rebeccah A. Urbiztondo, DVM, was a Master's student; Rashade A. H. Haynes, PhD, was a postdoctoral fellow; and Elaine Simpson, DVM, was a summer research student in the Department of Veterinary Biosciences at The Ohio State University in Columbus, Ohio. Stefan Niewiesk, PhD, DVM, is professor in the Department of Veterinary Biosciences at The Ohio State University is Columbus, Ohio. Michael D. Lairmore, DVM, PhD, is dean, in the School of Veterinary Medicine at the University of California, Davis in Davis, California
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The Microbiome, Timing, and Barrier Function in the Context of Allergic Disease. Immunity 2016; 44:728-38. [PMID: 27096316 DOI: 10.1016/j.immuni.2016.02.002] [Citation(s) in RCA: 104] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Indexed: 12/14/2022]
Abstract
Allergic disease affects millions. Despite many advances in our understanding of the immune system in the past century, the physiologic underpinning for the existence of allergy remains largely mysterious. Food allergies, in particular, have increased dramatically in recent years, adding a new sense of urgency to unraveling this mystery. The concurrence of significant lifestyle changes in Western societies with increasing disease prevalence implies a causal link. Demographic variables that influence the composition and function of the commensal microbiota early in life seem to be most important. Identifying the evolutionary and physiologic foundations of allergic disease and defining what about our modern environment is responsible for its increased incidence will provide insights critical to the development of new approaches to prevention and treatment.
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Sansone CL, Cohen J, Yasunaga A, Xu J, Osborn G, Subramanian H, Gold B, Buchon N, Cherry S. Microbiota-Dependent Priming of Antiviral Intestinal Immunity in Drosophila. Cell Host Microbe 2016; 18:571-81. [PMID: 26567510 DOI: 10.1016/j.chom.2015.10.010] [Citation(s) in RCA: 119] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Revised: 07/31/2015] [Accepted: 10/15/2015] [Indexed: 01/16/2023]
Abstract
Enteric pathogens must overcome intestinal defenses to establish infection. In Drosophila, the ERK signaling pathway inhibits enteric virus infection. The intestinal microflora also impacts immunity but its role in enteric viral infection is unknown. Here we show that two signals are required to activate antiviral ERK signaling in the intestinal epithelium. One signal depends on recognition of peptidoglycan from the microbiota, particularly from the commensal Acetobacter pomorum, which primes the NF-kB-dependent induction of a secreted factor, Pvf2. However, the microbiota is not sufficient to induce this pathway; a second virus-initiated signaling event involving release of transcriptional paused genes mediated by the kinase Cdk9 is also required for Pvf2 production. Pvf2 stimulates antiviral immunity by binding to the receptor tyrosine kinase PVR, which is necessary and sufficient for intestinal ERK responses. These findings demonstrate that sensing of specific commensals primes inflammatory signaling required for epithelial responses that restrict enteric viral infections.
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Affiliation(s)
- Christine L Sansone
- Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
| | - Jonathan Cohen
- Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
| | - Ari Yasunaga
- Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
| | - Jie Xu
- Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
| | - Greg Osborn
- Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
| | - Harry Subramanian
- Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
| | - Beth Gold
- Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
| | - Nicolas Buchon
- Department of Entomology, Cornell University, Ithaca, NY 14853, USA
| | - Sara Cherry
- Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
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Peyrin-Biroulet L, Chamaillard M. Invited review: NOD2 and defensins: translating innate to adaptive immunity in Crohn's disease. ACTA ACUST UNITED AC 2016; 13:135-9. [PMID: 17621555 DOI: 10.1177/0968051907080429] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The nucleotide-binding oligomerisation protein 2 (NOD2) is a sensor for bacterial muramyl dipeptide, which ensures ileal expression of antimicrobial peptides (so-called α-defensins) and promotes cytokine and chemokine production by immunocytes and enterocytes. Defective NOD2 signaling pathway and impaired expression of defensins were inextricably linked to the pathogenesis of Crohn's disease, a common form of inflammatory bowel disease. NOD2 and defensin deficiency at the level of the epithelial barrier and gut-associated lymphoid tissue may favour Crohn's disease by failing to protect from enteropathogens and to instruct adaptive immune response in the gut micro-environment. Herein, we provide an overview on the key role of NOD2 and defensins in antigen-presenting function of dendritic cells and antigen-specific immunity. We also outline the urgent need for a better understanding of the regulators of NOD2 function and defensin biogenesis to support the development of a rational immunostimulatory treatment for restoring long-lasting immunity in Crohn's disease.
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Lee JB. Regulation of IgE-Mediated Food Allergy by IL-9 Producing Mucosal Mast Cells and Type 2 Innate Lymphoid Cells. Immune Netw 2016; 16:211-8. [PMID: 27574500 PMCID: PMC5002447 DOI: 10.4110/in.2016.16.4.211] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 08/01/2016] [Accepted: 08/08/2016] [Indexed: 12/18/2022] Open
Abstract
Due to the increasing prevalence and number of life-threatening cases, food allergy has emerged as a major health concern. The classic immune response seen during food allergy is allergen-specific IgE sensitization and hypersensitivity reactions to foods occur in the effector phase with often severe and deleterious outcomes. Recent research has advanced understanding of the immunological mechanisms occurring during the effector phase of allergic reactions to ingested food. Therefore, this review will not only cover the mucosal immune system of the gastrointestinal tract and the immunological mechanisms underlying IgE-mediated food allergy, but will also introduce cells recently identified to have a role in the hypersensitivity reaction to food allergens. These include IL-9 producing mucosal mast cells (MMC9s) and type 2 innate lymphoid cells (ILC2s). The involvement of these cell types in potentiating the type 2 immune response and developing the anaphylactic response to food allergens will be discussed. In addition, it has become apparent that there is a collaboration between these cells that contributes to an individual's susceptibility to IgE-mediated food allergy.
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Affiliation(s)
- Jee-Boong Lee
- Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Korea
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McNamee EN, Rivera-Nieves J. Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur? Front Immunol 2016; 7:308. [PMID: 27579025 PMCID: PMC4985530 DOI: 10.3389/fimmu.2016.00308] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 07/29/2016] [Indexed: 12/15/2022] Open
Abstract
Organized lymphoid tissues like the thymus first appeared in jawed vertebrates around 500 million years ago and have evolved to equip the host with a network of specialized sites, strategically located to orchestrate strict immune-surveillance and efficient immune responses autonomously. The gut-associated lymphoid tissues maintain a mostly tolerant environment to dampen our responses to daily dietary and microbial products in the intestine. However, when this homeostasis is perturbed by chronic inflammation, the intestine is able to develop florid organized tertiary lymphoid tissues (TLT), which heralds the onset of regional immune dysregulation. While TLT are a pathologic hallmark of Crohn's disease (CD), their role in the overall process remains largely enigmatic. A critical question remains; are intestinal TLT generated by the immune infiltrated intestine to modulate immune responses and rebuild tolerance to the microbiota or are they playing a more sinister role by generating dysregulated responses that perpetuate disease? Herein, we discuss the main theories of intestinal TLT neogenesis and focus on the most recent findings that open new perspectives to their role in inflammatory bowel disease.
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Affiliation(s)
- Eóin N McNamee
- Mucosal Inflammation Program, Department of Anesthesiology, School of Medicine, University of Colorado - Anschutz Medical Campus , Aurora, CO , USA
| | - Jesús Rivera-Nieves
- Division of Gastroenterology, Inflammatory Bowel Disease Center, San Diego VAMC, University of California San Diego , La Jolla, CA , USA
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Olmos S, Blois S, Frecha C, Márquez G, Roux M. Cytokines Mediating Inflammation in a Model of Secondary Immunodeficiency in Wistar Rats: Immunomodulation Triggered by Thymomodulin. EUR J INFLAMM 2016. [DOI: 10.1177/1721727x0600400204] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
We have previously demonstrated in a rat model of immunodeficiency, an increase in the number of γδ T cells in the gut lamina propria and in the number of CD8αα+, CD25+, γδ+ subpopulations of intestinal intraepithelial lymphocytes (iIEL). The increased percentage of CD8αα+ iIEL that express CD25 indicates inflammation. The present study confirms the existence of an inflammatory process in the immunodeficient animals (R21) that is not detectable at the histological level but is characterized by an increase of the pro-inflammatory cytokines TNF-α and IFN-γ. We have shown a direct relationship between TNF receptor II (TNF-RII) expression and the higher levels of the γδ+ iIEL expressing TNF-α (TCRγδ+/TNF-α+ cells) that could be indicating a differential T cell reactivity. The effects of the increased expression of inflammatory cytokines such as TNF-α and INF-γ seem to be down regulated by the high levels of antigen specific TGF-β expression, which, we believe, is antigen specific and appears to maintain oral tolerance. Finally, in malnourished animals NF-κB remains principally in the cytosol and is unable to translocate to the nucleus, indicating the existence of alterations in the metabolic pathways leading to nuclear factor κB translocation from the cytoplasm to the nucleus. The therapeutic action of the immunomodulator TmB was demonstrated by its capacity to return all the cytokines studied to control levels. Moreover, its effects allowed the transcription factor NF-κB to translocate to the nucleus from the cytosol.
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Affiliation(s)
| | - S. Blois
- Faculty of Pharmacy and Biochemistry, IDEHU- Instituto de Estudios de Inmunidad Humoral, CONICET, University of Buenos Aires, Argentina
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Bonet MEB, Chaves AS, Mesón O, Perdigón G. Immunomodulatory and Anti-Inflammatory Activity Induced by Oral Administration of a Probiotic Strain of Lactobacillus Casei. EUR J INFLAMM 2016. [DOI: 10.1177/1721727x0600400104] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
The aim of this work was to study the effect of the long-term cyclic administration of the probiotic strain of Lactobacillus ( L.) casei CRL 431 as a mucosal immunomodulator of the immune cells associated with the lamina propria of the small intestine, bronchus and other immune cells not associated with mucosal tissues, such as peritoneal macrophages. BALB/c mice were orally administered with a suspension of Lc 109 cfu/day/animal in non-fat milk (NFM) 10% for two consecutive days, the optimal dose selected in previous studies to reach protective immunity. This administration was repeated cyclically every 5 days for 98 days. Mice in the control group received only NFM 10%. Samples were taken after two days of L. casei administration and every 14 days until day 98. The small intestine and lungs were removed for histological slices preparation. Haematoxilin-eosin stains were made for histological studies of the small intestine. The number of IgA producing cells in the lamina propria of the small intestine and in bronchus was determined by immunofluorescence assays. Regulatory (IL-4, IL-10) and proinflammatory (TNF-α, INF-γ) cytokines were measured in the gut. Peritoneal macrophages were collected during the same periods for phagocytosis assays. We determined an increase in the number of IgA+ cells in the lamina propria of the small intestine in all the periods assayed and in BALT only until day 28. The cytokines studied (IL-10, IL-4, TNF-α and INF-γ) increased in most of the periods assayed, the effect being more remarkable for the anti-inflammatory cytokines such as IL-4 and IL-10. INF-γ was also increased but no modifications in the histological studies of the small intestine were observed, suggesting other roles for this cytokine The phagocytic activity of PM increased for most of the periods assayed. We demonstrated that long-term cyclic oral L. casei administration favors mucosal immunity and modulates the immune response to maintain the homeostasis at the mucosal level.
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Affiliation(s)
- M. E. Bibas Bonet
- Cátedra de Inmunología, Instituto de Microbiología, Fac. de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán
| | - A. S. Chaves
- Cátedra de Inmunología, Instituto de Microbiología, Fac. de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán
- Centro de Referencia para Lactobacilos (CERELA-CONICET), Tucumán, Argentina
| | - O. Mesón
- Cátedra de Inmunología, Instituto de Microbiología, Fac. de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán
| | - G. Perdigón
- Cátedra de Inmunología, Instituto de Microbiología, Fac. de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán
- Centro de Referencia para Lactobacilos (CERELA-CONICET), Tucumán, Argentina
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Marasco G, Di Biase AR, Schiumerini R, Eusebi LH, Iughetti L, Ravaioli F, Scaioli E, Colecchia A, Festi D. Gut Microbiota and Celiac Disease. Dig Dis Sci 2016; 61:1461-72. [PMID: 26725064 DOI: 10.1007/s10620-015-4020-2] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Accepted: 12/20/2015] [Indexed: 12/18/2022]
Abstract
Recent evidence regarding celiac disease has increasingly shown the role of innate immunity in triggering the immune response by stimulating the adaptive immune response and by mucosal damage. The interaction between the gut microbiota and the mucosal wall is mediated by the same receptors which can activate innate immunity. Thus, changes in gut microbiota may lead to activation of this inflammatory pathway. This paper is a review of the current knowledge regarding the relationship between celiac disease and gut microbiota. In fact, patients with celiac disease have a reduction in beneficial species and an increase in those potentially pathogenic as compared to healthy subjects. This dysbiosis is reduced, but might still remain, after a gluten-free diet. Thus, gut microbiota could play a significant role in the pathogenesis of celiac disease, as described by studies which link dysbiosis with the inflammatory milieu in celiac patients. The use of probiotics seems to reduce the inflammatory response and restore a normal proportion of beneficial bacteria in the gastrointestinal tract. Additional evidence is needed in order to better understand the role of gut microbiota in the pathogenesis of celiac disease, and the clinical impact and therapeutic use of probiotics in this setting.
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Affiliation(s)
- Giovanni Marasco
- Department of Medical and Surgical Science, University of Bologna, 40138, Bologna, Italy.
| | | | - Ramona Schiumerini
- Department of Medical and Surgical Science, University of Bologna, 40138, Bologna, Italy
| | - Leonardo Henry Eusebi
- Department of Medical and Surgical Science, University of Bologna, 40138, Bologna, Italy
| | - Lorenzo Iughetti
- Department of Pediatrics, University of Modena, 41124, Modena, Italy
| | - Federico Ravaioli
- Department of Medical and Surgical Science, University of Bologna, 40138, Bologna, Italy
| | - Eleonora Scaioli
- Department of Medical and Surgical Science, University of Bologna, 40138, Bologna, Italy
| | - Antonio Colecchia
- Department of Medical and Surgical Science, University of Bologna, 40138, Bologna, Italy
| | - Davide Festi
- Department of Medical and Surgical Science, University of Bologna, 40138, Bologna, Italy
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Grootjans J, Lenaerts K, Buurman WA, Dejong CHC, Derikx JPM. Life and death at the mucosal-luminal interface: New perspectives on human intestinal ischemia-reperfusion. World J Gastroenterol 2016; 22:2760-2770. [PMID: 26973414 PMCID: PMC4777998 DOI: 10.3748/wjg.v22.i9.2760] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Revised: 09/24/2015] [Accepted: 12/14/2015] [Indexed: 02/06/2023] Open
Abstract
Intestinal ischemia is a frequently observed phenomenon. Morbidity and mortality rates are extraordinarily high and did not improve over the past decades. This is in part attributable to limited knowledge on the pathophysiology of intestinal ischemia-reperfusion (IR) in man, the paucity in preventive and/or therapeutic options and the lack of early diagnostic markers for intestinal ischemia. To improve our knowledge and solve clinically important questions regarding intestinal IR, we developed a human experimental intestinal IR model. With this model, we were able to gain insight into the mechanisms that allow the human gut to withstand short periods of IR without the development of severe inflammatory responses. The purpose of this review is to overview the most relevant recent advances in our understanding of the pathophysiology of human intestinal IR, as well as the (potential) future clinical implications.
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