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Estevinho MM, Midya V, Cohen-Mekelburg S, Allin KH, Fumery M, Pinho SS, Colombel JF, Agrawal M. Emerging role of environmental pollutants in inflammatory bowel disease risk, outcomes and underlying mechanisms. Gut 2025; 74:477-486. [PMID: 39179372 PMCID: PMC11802320 DOI: 10.1136/gutjnl-2024-332523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 08/09/2024] [Indexed: 08/26/2024]
Abstract
Epidemiological and translational data increasingly implicate environmental pollutants in inflammatory bowel disease (IBD). Indeed, the global incidence of IBD has been rising, particularly in developing countries, in parallel with the increased use of chemicals and synthetic materials in daily life and escalating pollution levels. Recent nationwide and ecological studies have reported associations between agricultural pesticides and IBD, particularly Crohn's disease. Exposure to other chemical categories has also been linked with an increased risk of IBD. To synthesise available data and identify knowledge gaps, we conducted a systematic review of human studies that reported on the impact of environmental pollutants on IBD risk and outcomes. Furthermore, we summarised in vitro data and animal studies investigating mechanisms underlying these associations. The 32 included human studies corroborate that heavy and transition metals, except zinc, air pollutants, per- and polyfluorinated substances, and pesticides are associated with an increased risk of IBD, with exposure to air pollutants being associated with disease-related adverse outcomes as well. The narrative review of preclinical studies suggests several overlapping mechanisms underlying these associations, including increased intestinal permeability, systemic inflammation and dysbiosis. A consolidated understanding of the impact of environmental exposures on IBD risk and outcomes is key to the identification of potentially modifiable risk factors and to inform strategies towards prediction, prevention and mitigation of IBD.
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Affiliation(s)
- Maria Manuela Estevinho
- Department of Gastroenterology, Unidade Local de Saúde Gaia Espinho, Vila Nova de Gaia, Portugal
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Vishal Midya
- Department of Environmental Medicine and Climate Science, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Shirley Cohen-Mekelburg
- Division of Gastroenterology and Hepatology, University of Michigan Medicine, Ann Arbor, Michigan, USA
- VA Center for Clinical Management Research, VA Ann Arbor Health Care System, Ann Arbor, Michigan, USA
| | - Kristine Højgaard Allin
- Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Mathurin Fumery
- Department of Gastroenterology, CHU Amiens and PériTox, UMR-I 01 INERIS, Picardie Jules Verne University, Amiens, France
| | - Salome S Pinho
- i3S, Institute for Research and Innovation in Health, Porto, Portugal
- ICBAS-School of Medicine and Biomedical Sciences, Porto, Portugal
- Faculty of Medicine, University of Porto, Porto, Portugal
| | - Jean-Frederic Colombel
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Manasi Agrawal
- Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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2
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Jomova K, Alomar SY, Nepovimova E, Kuca K, Valko M. Heavy metals: toxicity and human health effects. Arch Toxicol 2025; 99:153-209. [PMID: 39567405 PMCID: PMC11742009 DOI: 10.1007/s00204-024-03903-2] [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: 09/08/2024] [Accepted: 10/17/2024] [Indexed: 11/22/2024]
Abstract
Heavy metals are naturally occurring components of the Earth's crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·-), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO-). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.
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Affiliation(s)
- Klaudia Jomova
- Department of Chemistry, Faculty of Natural Sciences, Constantine The Philosopher University in Nitra, 949 74, Nitra, Slovakia
| | - Suliman Y Alomar
- Doping Research Chair, Zoology Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Sciences, University of Hradec Kralove, 50005, Hradec Kralove, Czech Republic
- Center of Advanced Innovation Technologies, VSB-Technical University of Ostrava, 708 00, Ostrava-Poruba, Czech Republic
| | - Kamil Kuca
- Center of Advanced Innovation Technologies, VSB-Technical University of Ostrava, 708 00, Ostrava-Poruba, Czech Republic
- Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
| | - Marian Valko
- Faculty of Chemical and Food Technology, Slovak University of Technology, 812 37, Bratislava, Slovakia.
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3
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Bonfiglio R, Giacobbi E, Palumbo V, Casciardi S, Sisto R, Servadei F, Scioli MP, Schiaroli S, Cornella E, Cervelli G, Sica G, Candi E, Melino G, Mauriello A, Scimeca M. Aluminum Concentration Is Associated with Tumor Mutational Burden and the Expression of Immune Response Biomarkers in Colorectal Cancers. Int J Mol Sci 2024; 25:13388. [PMID: 39769153 PMCID: PMC11676456 DOI: 10.3390/ijms252413388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 12/10/2024] [Accepted: 12/11/2024] [Indexed: 01/11/2025] Open
Abstract
Environmental pollution poses a significant risk to public health, as demonstrated by the bioaccumulation of aluminum (Al) in colorectal cancer (CRC). This study aimed to investigate the potential mutagenic effect of Al bioaccumulation in CRC samples, linking it to the alteration of key mediators of cancer progression, including immune response biomarkers. Aluminum levels in 20 CRC biopsy samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The results indicated that Al bioaccumulation occurred in 100% of the cases. A correlation between Al levels and tumor mutation burden was observed. Furthermore, RNA sequencing revealed a significant association between Al concentration and the expression of the immune checkpoint molecule CTLA-4. Although correlations with PD-1 and PD-L1 were not statistically significant, a trend was observed. Additionally, a correlation between Al levels and both the presence of myeloid cells and IFNγ expression was detected, linking Al exposure to inflammatory responses within the tumor microenvironment. These findings suggested that Al can play a role in CRC progression by promoting both genetic mutations and immune evasion. Given the ubiquitous presence of Al in industrial and consumer products, dietary sources, and environmental pollutants, these results underscored the need for stricter regulatory measures to control Al exposure.
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Affiliation(s)
- Rita Bonfiglio
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Erica Giacobbi
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Valeria Palumbo
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Stefano Casciardi
- Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL Research, Monte Porzio Catone, 00078 Rome, Italy; (S.C.); (R.S.)
| | - Renata Sisto
- Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL Research, Monte Porzio Catone, 00078 Rome, Italy; (S.C.); (R.S.)
| | - Francesca Servadei
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Maria Paola Scioli
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Stefania Schiaroli
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Elena Cornella
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Giulio Cervelli
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Giuseppe Sica
- Department of Surgery, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy
| | - Eleonora Candi
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Gerry Melino
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Alessandro Mauriello
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
| | - Manuel Scimeca
- Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.B.); (E.G.); (V.P.); (F.S.); (M.P.S.); (S.S.); (E.C.)
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4
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Li H, Yang Z, Liu Y, Sun P, Wu B, Chen L. Combined effects of polyvinyl chloride or polypropylene microplastics with cadmium on the intestine of zebrafish at environmentally relevant concentrations. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 954:176289. [PMID: 39288879 DOI: 10.1016/j.scitotenv.2024.176289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 09/03/2024] [Accepted: 09/13/2024] [Indexed: 09/19/2024]
Abstract
Cadmium (Cd) is a common additive in polyvinyl chloride (PVC) and polypropylene (PP) plastics. Aquatic organisms were inevitably co-exposed to PVC/PP microplastics (MPs) and Cd, but their combined toxicity is still unknown. In this study, adult zebrafish were exposed to 200 μg/L MPs (PVC or PP) and 10 μg/L Cd alone or in combination for 28 days to investigate their toxicity and mechanisms. Results showed that combined exposure with PVC/PP enhanced the Cd accumulation in the zebrafish intestine. Subsequently, toxicology analyses showed that both PVC and PP possessed synergistic toxicity with Cd, manifested by the exfoliation and necrosis of intestinal epithelial cells, and increased levels of interleukin-1β (IL-1β), superoxide dismutase (SOD) and malondialdehyde (MDA). PP exhibited a stronger synergistic effect than PVC. Integration of non-targeted metabolomics and 16S rRNA gene sequencing revealed that combined exposure to PVC and Cd induced intestine toxicity mainly through bile acid (BA) biosynthesis, fructose (Fru) and mannose (Man) metabolism, and pentose phosphate pathway (PPP). The combined exposure of PP and Cd induced toxicity through the arginine (Arg) and glutathione (GSH) metabolisms. Meanwhile, combined exposure of PVC/PP and Cd increased the abundance of intestinal Proteobacteria and pathogen Vibrio, and decreased the abundance of Gemmobacter. These changes indrectly promoted the synergistic toxicity of PVC/PP and Cd through metabolites, such as indole-3-pyruvate (IPyA), chenodeoxycholic acid (CDCA), and cholic acid (CA). These findings highlighted that more attention should be paid to the toxicity of chemicals at environmentally relevant concentrations, particularly those co-existing with MPs.
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Affiliation(s)
- Huan Li
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210023, PR China
| | - Zhongchao Yang
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210023, PR China
| | - Yuxuan Liu
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210023, PR China
| | - Peipei Sun
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210023, PR China
| | - Bing Wu
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210023, PR China
| | - Ling Chen
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210023, PR China.
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5
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Walraven T, Busch M, Wang J, Donkers JM, Duijvestein M, van de Steeg E, Kramer NI, Bouwmeester H. Elevated risk of adverse effects from foodborne contaminants and drugs in inflammatory bowel disease: a review. Arch Toxicol 2024; 98:3519-3541. [PMID: 39249550 PMCID: PMC11489187 DOI: 10.1007/s00204-024-03844-w] [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: 06/04/2024] [Accepted: 08/19/2024] [Indexed: 09/10/2024]
Abstract
The global burden of Inflammatory bowel disease (IBD) has been rising over the last decades. IBD is an intestinal disorder with a complex and largely unknown etiology. The disease is characterized by a chronically inflamed gastrointestinal tract, with intermittent phases of exacerbation and remission. This compromised intestinal barrier can contribute to, enhance, or even enable the toxicity of drugs, food-borne chemicals and particulate matter. This review discusses whether the rising prevalence of IBD in our society warrants the consideration of IBD patients as a specific population group in toxicological safety assessment. Various in vivo, ex vivo and in vitro models are discussed that can simulate hallmarks of IBD and may be used to study the effects of prevalent intestinal inflammation on the hazards of these various toxicants. In conclusion, risk assessments based on healthy individuals may not sufficiently cover IBD patient safety and it is suggested to consider this susceptible subgroup of the population in future toxicological assessments.
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Affiliation(s)
- Tom Walraven
- Division of Toxicology, Wageningen University and Research, Wageningen, The Netherlands.
| | - Mathias Busch
- Division of Toxicology, Wageningen University and Research, Wageningen, The Netherlands
| | - Jingxuan Wang
- Division of Toxicology, Wageningen University and Research, Wageningen, The Netherlands
| | - Joanne M Donkers
- Department of Metabolic Health Research, Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands
| | - Marjolijn Duijvestein
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Evita van de Steeg
- Department of Metabolic Health Research, Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands
| | - Nynke I Kramer
- Division of Toxicology, Wageningen University and Research, Wageningen, The Netherlands
| | - Hans Bouwmeester
- Division of Toxicology, Wageningen University and Research, Wageningen, The Netherlands
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Zhong Q, Pan X, Chen Y, Lian Q, Gao J, Xu Y, Wang J, Shi Z, Cheng H. Prosthetic Metals: Release, Metabolism and Toxicity. Int J Nanomedicine 2024; 19:5245-5267. [PMID: 38855732 PMCID: PMC11162637 DOI: 10.2147/ijn.s459255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 05/13/2024] [Indexed: 06/11/2024] Open
Abstract
The development of metallic joint prostheses has been ongoing for more than a century alongside advancements in hip and knee arthroplasty. Among the materials utilized, the Cobalt-Chromium-Molybdenum (Co-Cr-Mo) and Titanium-Aluminum-Vanadium (Ti-Al-V) alloys are predominant in joint prosthesis construction, predominantly due to their commendable biocompatibility, mechanical strength, and corrosion resistance. Nonetheless, over time, the physical wear, electrochemical corrosion, and inflammation induced by these alloys that occur post-implantation can cause the release of various metallic components. The released metals can then flow and metabolize in vivo, subsequently causing potential local or systemic harm. This review first details joint prosthesis development and acknowledges the release of prosthetic metals. Second, we outline the metallic concentration, biodistribution, and elimination pathways of the released prosthetic metals. Lastly, we discuss the possible organ, cellular, critical biomolecules, and significant signaling pathway toxicities and adverse effects that arise from exposure to these metals.
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Affiliation(s)
- Qiang Zhong
- Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Xin Pan
- Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Yuhang Chen
- Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Qiang Lian
- Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Jian Gao
- Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Yixin Xu
- Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Jian Wang
- Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Zhanjun Shi
- Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Hao Cheng
- Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
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Whelan K, Bancil AS, Lindsay JO, Chassaing B. Ultra-processed foods and food additives in gut health and disease. Nat Rev Gastroenterol Hepatol 2024; 21:406-427. [PMID: 38388570 DOI: 10.1038/s41575-024-00893-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/05/2024] [Indexed: 02/24/2024]
Abstract
Ultra-processed foods (UPFs) and food additives have become ubiquitous components of the modern human diet. There is increasing evidence of an association between diets rich in UPFs and gut disease, including inflammatory bowel disease, colorectal cancer and irritable bowel syndrome. Food additives are added to many UPFs and have themselves been shown to affect gut health. For example, evidence shows that some emulsifiers, sweeteners, colours, and microparticles and nanoparticles have effects on a range of outcomes, including the gut microbiome, intestinal permeability and intestinal inflammation. Broadly speaking, evidence for the effect of UPFs on gut disease comes from observational epidemiological studies, whereas, by contrast, evidence for the effect of food additives comes largely from preclinical studies conducted in vitro or in animal models. Fewer studies have investigated the effect of UPFs or food additives on gut health and disease in human intervention studies. Hence, the aim of this article is to critically review the evidence for the effects of UPF and food additives on gut health and disease and to discuss the clinical application of these findings.
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Affiliation(s)
- Kevin Whelan
- Department of Nutritional Sciences, King's College London, London, UK.
| | - Aaron S Bancil
- Department of Nutritional Sciences, King's College London, London, UK
| | - James O Lindsay
- Blizard Institute, Queen Mary University of London, Barts and the London School of Medicine, London, UK
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8
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Lin Z, Luo W, Zhang K, Dai S. Environmental and Microbial Factors in Inflammatory Bowel Disease Model Establishment: A Review Partly through Mendelian Randomization. Gut Liver 2024; 18:370-390. [PMID: 37814898 PMCID: PMC11096900 DOI: 10.5009/gnl230179] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 07/09/2023] [Accepted: 07/24/2023] [Indexed: 10/11/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a complex condition resulting from environmental, microbial, immunologic, and genetic factors. With the advancement of Mendelian randomization research in IBD, we have gained new insights into the relationship between these factors and IBD. Many animal models of IBD have been developed using different methods, but few studies have attempted to model IBD by combining environmental factors and microbial factors. In this review, we examine how environmental factors and microbial factors affect the development and progression of IBD, and how they interact with each other and with the intestinal microbiota. We also summarize the current methods for creating animal models of IBD and compare their advantages and disadvantages. Based on the latest findings from Mendelian randomization studies on the role of environmental factors in IBD, we discuss which environmental and microbial factors could be used to construct a more realistic and reliable IBD experimental model. We propose that animal models of IBD should consider both environmental and microbial factors to better mimic human IBD pathogenesis and to reveal the underlying mechanisms of IBD at the immune and genetic levels. We highlight the importance of environmental and microbial factors in IBD pathogenesis and offer new perspectives and suggestions for improving experimental animal modeling. Our goal is to create a model that closely resembles the clinical picture of IBD.
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Affiliation(s)
- Zesheng Lin
- The First Clinical Medical School, Southern Medical University, Guangzhou, China
| | - Wenjing Luo
- The Second Clinical Medical School, Southern Medical University, Guangzhou, China
| | - Kaijun Zhang
- Department of Gastroenterology, Guangdong Provincial Geriatrics Institute, Guangzhou, ChinaNational Key Clinical Specialty, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Shixue Dai
- Department of Gastroenterology, Guangdong Provincial Geriatrics Institute, Guangzhou, ChinaNational Key Clinical Specialty, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Department of Gastroenterology, Geriatric Center, National Regional Medical Center, Ganzhou Hospital Affiliated to Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Ganzhou, China
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9
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Bonfiglio R, Sisto R, Casciardi S, Palumbo V, Scioli MP, Palumbo A, Trivigno D, Giacobbi E, Servadei F, Melino G, Mauriello A, Scimeca M. The impact of toxic metal bioaccumulation on colorectal cancer: Unravelling the unexplored connection. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 906:167667. [PMID: 37813250 DOI: 10.1016/j.scitotenv.2023.167667] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 10/03/2023] [Accepted: 10/06/2023] [Indexed: 10/11/2023]
Abstract
Colorectal cancer is a major public health concern, with increasing incidence and mortality rates worldwide. Environmental factors, including exposure to toxic metals, such as lead, chromium, cadmium, aluminium, copper, arsenic and mercury, have been suggested to play a significant role in the development and progression of this neoplasia. In particular, the bioaccumulation of toxic metals can play a significant role in colorectal cancer by regulating biological phenomenon associated to both cancer occurrence and progression, such as cell death and proliferation. Also, frequently these metals can induce DNA mutations in well-known oncogenes. This review provides a critical analysis of the current evidence, highlighting the need for further research to fully grasp the complex interplay between toxic metal bioaccumulation and colorectal cancer. Understanding the contribution of toxic metals to colorectal cancer occurrence and progression is essential for the development of targeted preventive strategies and social interventions, with the ultimate goal of reducing the burden of this disease.
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Affiliation(s)
- Rita Bonfiglio
- Department of Experimental Medicine, Torvergata Oncoscience Research, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
| | - Renata Sisto
- Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, National Institute for Insurance against Accidents at Work (INAIL), Rome, Italy.
| | - Stefano Casciardi
- Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, National Institute for Insurance against Accidents at Work (INAIL), Rome, Italy.
| | - Valeria Palumbo
- Department of Experimental Medicine, Torvergata Oncoscience Research, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Maria Paola Scioli
- Department of Experimental Medicine, Torvergata Oncoscience Research, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Alessia Palumbo
- Department of Experimental Medicine, Torvergata Oncoscience Research, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
| | - Donata Trivigno
- Department of Experimental Medicine, Torvergata Oncoscience Research, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Erica Giacobbi
- Department of Experimental Medicine, Torvergata Oncoscience Research, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Francesca Servadei
- Department of Experimental Medicine, Torvergata Oncoscience Research, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy
| | - Gerry Melino
- Department of Experimental Medicine, Torvergata Oncoscience Research, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
| | - Alessandro Mauriello
- Department of Experimental Medicine, Torvergata Oncoscience Research, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
| | - Manuel Scimeca
- Department of Experimental Medicine, Torvergata Oncoscience Research, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
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10
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Liu S, Liu Y, Zhang D, Li H, Shao X, Xie P, Li J. Novel insights into perfluorinated compound-induced hepatotoxicity: Chronic dietary restriction exacerbates the effects of PFBS on hepatic lipid metabolism in mice. ENVIRONMENT INTERNATIONAL 2023; 181:108274. [PMID: 37879206 DOI: 10.1016/j.envint.2023.108274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 10/13/2023] [Accepted: 10/16/2023] [Indexed: 10/27/2023]
Abstract
Perfluorobutane sulfonates (PFBS) have garnered extensive utilization because of their distinctive physicochemical properties. The liver acts as a key target organ for toxicity within the body and is vital for regulating metabolic processes, particularly lipid metabolism. However, there is currently a significant research gap regarding the influences of PFBS on hepatic lipid metabolism, especially in individuals with different dietary statuses. Here, the objective of this research was to examine the effects of PFBS on hepatic function under different dietary conditions. The results suggested that the levels of liver injury biomarkers were significantly upregulated, e.g., transaminase (GPT, GOT), while liver lipid levels were downregulated after exposure to PFBS at concentration of 50 μg/L for 42 days. Moreover, restricted diet further intensified the adverse effects of PFBS on the liver. Metabolomics analysis identified significant alterations in lipid-related metabolites in PFBS-induced hepatotoxicity, PFBS exposure induced a decrease in lysophosphatidylethanolamine and lysophosphatidylcholine. PFBS exposure caused an increase in aldosterone and prostaglandin f2alpha under restricted diet. In PFBS treatment group, histidine metabolism, beta-alanine metabolism, and arginine biosynthesis were the main pathway for PFBS toxicity. Aldosterone-regulated sodium reabsorption as a vital factor in inducing PFBS toxicity in the RD-PFBS treatment group. The analysis of 16S rRNA sequencing revealed that exposure to PFBS resulted in imbalance of gut microbial communities. PFBS exposure induced a decrease in Akkermansia and Lactobacillus, but an increase in Enterococcus. PFBS exposure caused the abundance of Lachnospiraceae_NK4A136_group was significantly elevated under restricted diet. Additionally, disruptions in the expression of genes involved in lipid production and consumption may significantly contribute to lipid imbalance in the liver. This study underscores the importance of recognizing the harmful impact of PFBS on liver function, along with the biotoxicity of contaminant influenced by dietary habits.
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Affiliation(s)
- Su Liu
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China; School of Engineering, China Pharmaceutical University, Nanjing 211198, China
| | - Yafeng Liu
- School of Engineering, China Pharmaceutical University, Nanjing 211198, China
| | - Dong Zhang
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China
| | - Huan Li
- School of Engineering, China Pharmaceutical University, Nanjing 211198, China; State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210023, China
| | - Xicheng Shao
- Faculty of Land and Food Systems, Vancouver Campus, University of British Columbia, Vancouver V6T 1Z4, Canada
| | - Pengfei Xie
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China
| | - Jianmei Li
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.
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11
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Makevic V, Milovanovich ID, Popovac N, Janković S, Janković V, Stefanović S, Bukumiric Z, de Luka SR. Oligoelements in serum and intestinal tissue of pediatric IBD patients. J Trace Elem Med Biol 2023; 79:127239. [PMID: 37302217 DOI: 10.1016/j.jtemb.2023.127239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 05/21/2023] [Accepted: 06/02/2023] [Indexed: 06/13/2023]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) develops through complex interplay of genetic, microbial, immune, and environmental factors. Trace elements alterations are commonly present in IBD and may have influence on IBD development. Heavy metal pollution is one of the major environmental issues nowadays and IBD incidence is rising in countries where industry starts to develop. Metals are implicated in processes that are connected to IBD pathogenesis. AIM The aim of this study was to investigate toxic and trace element levels in pediatric population of IBD patients both in serum and intestinal mucosa. MATERIALS AND METHODS This prospective study enrolled children newly diagnosed with IBD in University children's hospital in Belgrade. Concentrations of thirteen elements: Al, As, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Se and Zn in serum and intestinal mucosa of 17 newly diagnosed children with IBD (10 Crohn's disease (CD) and 7ulcerative colitis (UC)) and 10 controls were assessed using inductively coupled plasma mass spectrometry (ICP-MS). Intestinal mucosa samples were taken from terminal ileum and six different colon segments (cecum, ascending colon, colon transversum, descending and sigmoid colon and rectum). RESULTS The results demonstrated significant alterations in serum and intestinal mucosa concentrations of investigated elements. Serum iron was significantly decreased in IBD and CD group, compared to controls while serum Cu significantly differed between three investigated groups with highest concentration observed in CD children. Serum manganese was the highest in the UC subgroup. Terminal ileums of IBD patients contained significantly lower amount of Cu, Mg, Mn and Zn with Mn being significantly decreased also in CD patients compared to control. IBD patients' caecum contained significantly less Mg and Cu while colon transversum tissue samples from IBD and Crohn's patients contained significantly more chromium than controls. Moreover, sigmoid colon of IBD patients were poorer in Mg than controls (p < 0.05). Colon Al, As and Cd were significantly reduced in IBD, and UC children compared to control. Correlations of investigated elements in CD and UC groups were different from controls. Biochemical and clinical parameters showed correlation with element concentrations in intestines. CONCLUSION Sera of CD, UC and control children significantly differ in Fe, Cu and Mn levels. Serum manganese was the highest in the UC subgroup creating the most prominent and only significant difference between UC and CD subgroups. Terminal ileum of IBD patients contained significantly lower amount of majority of investigated essential trace elements and toxic elements were significantly reduced in colon of IBD and UC patients. Investigation of macro- and microelement alterations in children and adults has potential to further elucidate IBD pathogenesis.
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Affiliation(s)
- Vedrana Makevic
- Department of Pathological Physiology, Faculty of Medicine, University of Belgrade, Dr Subotica1, 11000 Belgrade, Serbia.
| | | | - Nevena Popovac
- University Children's Hospital, Tiršova 10, 11000 Belgrade, Serbia.
| | - Saša Janković
- Institute of Meat Hygiene and Technology, Kaćanskog 13, 11000 Belgrade, Serbia.
| | - Vesna Janković
- Institute of Meat Hygiene and Technology, Kaćanskog 13, 11000 Belgrade, Serbia.
| | - Srdjan Stefanović
- Institute of Meat Hygiene and Technology, Kaćanskog 13, 11000 Belgrade, Serbia.
| | - Zoran Bukumiric
- Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Dr Subotica 15, 11000 Belgrade, Serbia.
| | - Silvio R de Luka
- Department of Pathological Physiology, Faculty of Medicine, University of Belgrade, Dr Subotica1, 11000 Belgrade, Serbia.
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12
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Djouina M, Waxin C, Leprêtre F, Tardivel M, Tillement O, Vasseur F, Figeac M, Bongiovanni A, Sebda S, Desreumaux P, Launay D, Dubuquoy L, Body-Malapel M, Vignal C. Gene/environment interaction in the susceptibility of Crohn's disease patients to aluminum. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 850:158017. [PMID: 35973536 DOI: 10.1016/j.scitotenv.2022.158017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 08/09/2022] [Accepted: 08/09/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND & AIM The key role of environmental factors in the pathogenesis of Inflammatory Bowel Diseases (IBD) is recognized. Aluminum is suspected to be a risk factor for IBD. However, mechanisms linking aluminum exposure to disease development are unknown. We examined the role of aluminum transport and subcellular localisation on human colon susceptibility to aluminum-induced inflammation. METHODS Human colon biopsies isolated from Crohn's disease (CD) or control patients and Caco-2 cells were incubated with aluminum. The effects of aluminum were evaluated on cytokine secretion and transporter expression. The role of aluminum kinetics parameters was studied in Caco-2 using transport inhibitors and in human colon biopsies by assessing genetic polymorphisms of transporters. RESULTS Aluminum exposure was shown to induce cytokine secretion in colon of CD but not healthy patients. In Caco-2 cells, aluminum internalisation was correlated with inflammatory status. In human colon, analysis of genetic polymorphisms and expression of ABCB1 and SLC26A3 transporters showed that their decreased activity was involved in aluminum-induced inflammation. CONCLUSIONS We hypothesize that alteration in detoxifying response would lead to a deregulation of intestinal homeostasis and to the expression of IBD. Our study emphasizes the complexity of gene/environment interaction for aluminum adverse health effect, highlighting at risk populations or subtypes of patients. A better understanding of correlations between gene expression or SNP and xenobiotic kinetics parameters would shift the medical paradigm to more personalized disease management and treatment.
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Affiliation(s)
- Madjid Djouina
- Univ. Lille, Inserm, CHU Lille, U1286- INFINITE - Institute for translational research in inflammation, F-59000 Lille, France
| | - Christophe Waxin
- Univ. Lille, Inserm, CHU Lille, U1286- INFINITE - Institute for translational research in inflammation, F-59000 Lille, France
| | - Frédéric Leprêtre
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, F-59000 Lille, France
| | - Meryem Tardivel
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, F-59000 Lille, France
| | - Olivier Tillement
- Institut Lumière Matière, Université Claude Bernard Lyon 1, CNRS UMR 5306, 69622 Villeurbanne, France
| | - Francis Vasseur
- Univ. Lille, CHU Lille, ULR 2694-METRICS : Évaluation des technologies de santé et des pratiques médicales, F-59000 Lille, France
| | - Martin Figeac
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, F-59000 Lille, France
| | - Antonino Bongiovanni
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, F-59000 Lille, France
| | - Shéhérazade Sebda
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, F-59000 Lille, France
| | - Pierre Desreumaux
- Univ. Lille, Inserm, CHU Lille, U1286- INFINITE - Institute for translational research in inflammation, F-59000 Lille, France
| | - David Launay
- Univ. Lille, Inserm, CHU Lille, U1286- INFINITE - Institute for translational research in inflammation, F-59000 Lille, France
| | - Laurent Dubuquoy
- Univ. Lille, Inserm, CHU Lille, U1286- INFINITE - Institute for translational research in inflammation, F-59000 Lille, France
| | - Mathilde Body-Malapel
- Univ. Lille, Inserm, CHU Lille, U1286- INFINITE - Institute for translational research in inflammation, F-59000 Lille, France
| | - Cécile Vignal
- Univ. Lille, Inserm, CHU Lille, U1286- INFINITE - Institute for translational research in inflammation, F-59000 Lille, France.
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13
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Aguilera-Lizarraga J. Gut reactions: emerging mechanisms of abdominal pain from food intake. Am J Physiol Gastrointest Liver Physiol 2022; 323:G401-G409. [PMID: 36126222 DOI: 10.1152/ajpgi.00173.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Abdominal pain, which is a form of visceral pain, is a highly prevalent symptom worldwide frequently occurring following food ingestion. Its pathophysiology is complex, and many factors, including intestinal environmental cues, the immune system, or the molecular composition of foods, can influence the development of postprandial abdominal pain. Because of the poor efficacy of drug treatments, current strategies are often limited to the exclusion of culprit food(s) from the diet. However, there are two important limitations to this approach. First, patients suffering from food-induced abdominal pain usually recognize several food items as the cause of their gastrointestinal symptoms. Second, not all offending foods can always be identified by these patients. Newly identified mechanisms involving neuroimmune interactions and their communication with the intestinal microbiota shed light on the development of new therapeutic strategies. In this Mini-Review, these novel mechanisms and relevance of such findings are highlighted.
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Affiliation(s)
- Javier Aguilera-Lizarraga
- Laboratory for Intestinal Neuroimmune Interactions, Translational Research Centre for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
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14
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Tarawneh R, Penhos E. The gut microbiome and Alzheimer's disease: Complex and bidirectional interactions. Neurosci Biobehav Rev 2022; 141:104814. [PMID: 35934087 PMCID: PMC9637435 DOI: 10.1016/j.neubiorev.2022.104814] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 07/16/2022] [Accepted: 08/01/2022] [Indexed: 11/20/2022]
Abstract
Structural and functional alterations to the gut microbiome, referred to as gut dysbiosis, have emerged as potential key mediators of neurodegeneration and Alzheimer disease (AD) pathogenesis through the "gut -brain" axis. Emerging data from animal and clinical studies support an important role for gut dysbiosis in mediating neuroinflammation, central and peripheral immune dysregulation, abnormal brain protein aggregation, and impaired intestinal and brain barrier permeability, leading to neuronal loss and cognitive impairment. Gut dysbiosis has also been shown to directly influence various mechanisms involved in neuronal growth and repair, synaptic plasticity, and memory and learning functions. Aging and lifestyle factors including diet, exercise, sleep, and stress influence AD risk through gut dysbiosis. Furthermore, AD is associated with characteristic gut microbial signatures which offer value as potential markers of disease severity and progression. Together, these findings suggest the presence of a complex bidirectional relationship between AD and the gut microbiome and highlight the utility of gut modulation strategies as potential preventative or therapeutic strategies in AD. We here review the current literature regarding the role of the gut-brain axis in AD pathogenesis and its potential role as a future therapeutic target in AD treatment and/or prevention.
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Affiliation(s)
- Rawan Tarawneh
- Department of Neurology, Center for Memory and Aging, Alzheimer Disease Research Center, The University of New Mexico, Albuquerque, NM 87106, USA.
| | - Elena Penhos
- College of Medicine, The Ohio State University, Columbus, OH, USA 43210
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15
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Liu S, Li H, Wang J, Wu B, Guo X. Polystyrene microplastics aggravate inflammatory damage in mice with intestinal immune imbalance. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 833:155198. [PMID: 35427627 DOI: 10.1016/j.scitotenv.2022.155198] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 03/17/2022] [Accepted: 04/08/2022] [Indexed: 06/14/2023]
Abstract
Microplastics (MPs) have been detected in drinking water, seafood, and commodities relevant to human daily life, causing widespread concern. Although there have been studies on the health risks of MPs to mammals, the impact of MPs on populations with intestinal immune imbalance has been greatly ignored. The vulnerability of the body with intestinal immune imbalance may increase the likelihood of its response to MPs, which is in urgent need of relevant research. Here, we compared the effects of 500 μg/L polystyrene microplastics (PSMPs) on healthy mice and mice with intestinal immune imbalance through colon photographs, histopathological analysis, expression of inflammatory cytokines, PSMPs distribution, microbial community analysis, and metabolomics analysis. The results demonstrated that intestinal immune imbalance aggravated the colonic response to PSMPs. PSMPs exposure significantly increased the expression of inflammation factors (TNF-α, IL-1β and IFN-γ) in mice with intestinal immune imbalance. In addition, the exposure of PSMPs aggravated the histopathological damage of colonic mucosa in mice with intestinal immune imbalance, and exerted great disturbance on the colonic microbial community and metabolism. This may be due to the significant increase of PSMPs accumulation owing to the damage of intestinal barrier in mice with intestinal immune imbalance. In addition, the increase of several pathogenic bacteria including Bacteroides caused by intestinal immune imbalance also increased the toxicity of PSMPs. Our results highlight that individual with intestinal immune imbalance could be more sensitive to environmental pollution, which should be considered during health risk assessment.
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Affiliation(s)
- Su Liu
- School of Engineering, China Pharmaceutical University, Nanjing 211198, China; School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.
| | - Huan Li
- School of Engineering, China Pharmaceutical University, Nanjing 211198, China
| | - Jun Wang
- School of Engineering, China Pharmaceutical University, Nanjing 211198, China
| | - Bing Wu
- State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing 210023, China
| | - Xuechao Guo
- Beijing Enterprises Water Group Limited, Beijing 100102, China
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16
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Hao W, Zhu X, Liu Z, Song Y, Wu S, Lu X, Yang J, Jin C. Resveratrol alleviates aluminum-induced intestinal barrier dysfunction in mice. ENVIRONMENTAL TOXICOLOGY 2022; 37:1373-1381. [PMID: 35156769 DOI: 10.1002/tox.23490] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 01/27/2022] [Accepted: 02/05/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Aluminum is mainly exposed to the general population through food and water, and is absorbed into the systemic circulation through intestine, which in turn damages the intestinal barrier. METHODS The mice model of subchronic exposure to aluminum chloride (AlCl3 ) was established via oral. Tail suspension test was used to detect depressive behavior. H&E staining was performed to assess pathological intestinal injury. Intestinal permeability was estimated by exogenous Evans blue content. The level of inflammatory cytokines and tight junction protein were assessed via ELISA and western blotting. Simultaneously, resveratrol (Rsv, an agonist of Sirt1) was evaluated the protective role against intestinal barrier injuries caused by aluminum exposure. RESULTS Our results showed that AlCl3 induced depressive-like behavior, intestinal pathological damage and intestinal barrier permeability, resulting in intestinal barrier dysfunction. Besides, aluminum induced the expression of inflammatory cytokines, which further triggered IRF8-MMP9-mediated downregulation of tight junction proteins including CLD1, OCLD and ZO-1. After Rsv treatment, SIRT1 expression was increased, depressive symptom was improved, pathological injury was reduced, inflammatory reaction was alleviated, and intestinal barrier function restored. CONCLUSION Our findings revealed that aluminum exposure induced intestinal barrier dysfunction by IRF8-MMP9 signaling pathway. Rsv alleviated these injuries via activating SIRT1.
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Affiliation(s)
- Wudi Hao
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, China
| | - Xiaoying Zhu
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, China
| | - Ziyue Liu
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, China
| | - Yushuai Song
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, China
| | - Shengwen Wu
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, China
| | - Xiaobo Lu
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, China
| | - Jinghua Yang
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, China
| | - Cuihong Jin
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, China
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17
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Abstract
Crohn's disease (CD) is chronic immune-related disease of the gastrointestinal tract hypothesized to be caused by an interplay of genetic predisposition and environmental exposures. With the global incidence increasing, more patients are exploring dietary exposures to explain and treat CD. However, most patients report minimal nutritional education from their provider, and providers report few nutritional resources to help them educate patients. This highlights the previous deficit of literature describing the role and influence of diet in CD. To address this need, this article reviews available literature on the possible roles of diet in the pathogenesis, exacerbation, and treatment of CD.
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Affiliation(s)
- Phillip Gu
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
| | - Linda A Feagins
- Department of Medicine, Center for Inflammatory Bowel Diseases, University of Texas at Austin, Dell Medical School, Health Discovery Building, Z0900 1601 Trinity Street, Building B, Austin, TX 78712, USA.
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18
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Lo CH, Khandpur N, Rossato SL, Lochhead P, Lopes EW, Burke KE, Richter JM, Song M, Korat AVA, Sun Q, Fung TT, Khalili H, Chan AT, Ananthakrishnan AN. Ultra-processed Foods and Risk of Crohn's Disease and Ulcerative Colitis: A Prospective Cohort Study. Clin Gastroenterol Hepatol 2022; 20:e1323-e1337. [PMID: 34461300 PMCID: PMC8882700 DOI: 10.1016/j.cgh.2021.08.031] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 08/23/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The rising incidence of inflammatory bowel disease in regions undergoing Westernization has coincided with the increase in ultra-processed food (UPF) consumption over the past few decades. We aimed to examine the association between consumption of UPFs and the risk of Crohn's disease (CD) and ulcerative colitis (UC). METHODS We performed a prospective cohort study of 3 nationwide cohorts of health professionals in the United States-the Nurses' Health Study (1986-2014), the Nurses' Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2012). We employed Cox proportional hazards models with adjustment for confounders to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CD and UC according to self-reported consumption of UPFs. RESULTS The study included 245,112 participants. Over 5,468,444 person-years of follow-up, we documented 369 incident cases of CD and 488 incident cases of UC. The median age at diagnosis was 56 years (range, 29-85 years). Compared with participants in the lowest quartile of simple updated UPF consumption, those in the highest quartile had a significantly increased risk of CD (HR, 1.70; 95% CI, 1.23-2.35; Ptrend = .0008). Among different UPF subgroups, ultra-processed breads and breakfast foods; frozen or shelf-stable ready-to-eat/heat meals; and sauces, cheeses, spreads, and gravies showed the strongest positive associations with CD risk (HR per 1 standard deviation increase in intake, 1.18 [95% CI, 1.07-1.29], 1.11 [95% CI, 1.01-1.22], and 1.14 [95% CI, 1.02-1.27], respectively). There was no consistent association between UPF intake and UC risk. CONCLUSIONS Higher UPF intake was associated with an increased risk of incident CD. Further studies are needed to identify specific contributory dietary components.
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Affiliation(s)
- Chun-Han Lo
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Neha Khandpur
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Department of Nutrition, School of Public Health, University of São Paulo, São Paulo, Brazil,Center for Epidemiological Studies in Health and Nutrition, Faculty of Public Health, University of São Paulo, São Paulo, Brazil
| | - Sinara Laurini Rossato
- Graduation course in Public Health, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
| | - Paul Lochhead
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Emily W. Lopes
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Kristin E. Burke
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - James M. Richter
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Mingyang Song
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Andres Victor Ardisson Korat
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Qi Sun
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Teresa T. Fung
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA,Department of Nutrition, Simmons University, Boston, Massachusetts, USA
| | - Hamed Khalili
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Andrew T. Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA,Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Ashwin N. Ananthakrishnan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA,Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
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19
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Ganesan N, Ronsmans S, Vanoirbeek J, Hoet PHM. Assessment of Experimental Techniques That Facilitate Human Granuloma Formation in an In Vitro System: A Systematic Review. Cells 2022; 11:cells11050864. [PMID: 35269486 PMCID: PMC8909410 DOI: 10.3390/cells11050864] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/14/2022] [Accepted: 02/28/2022] [Indexed: 12/12/2022] Open
Abstract
The process of granuloma formation is complex, and due to species differences, the validity of animal studies is somewhat questioned. Moreover, the large number of animals needed to observe the different stages of development also raises ethical questions. Therefore, researchers have explored the use of human peripheral blood mononuclear cells (PBMCs), a heterogeneous population of immune cells, in an in vitro model. This review included in vitro studies that focused on exposing PBMCs—from healthy, sensitized, or diseased individuals—to antigens derived from infectious agents—such as mycobacteria or Schistosoma spp.—or inorganic antigens—such as beryllium. The reviewed studies mainly explored how human in vitro granuloma models can contribute towards understanding the pathogenesis of granulomatous diseases, especially during the early stages of granuloma formation. The feasibility of granuloma modelling was thus largely assessed via experimental techniques including (1) granuloma scoring indices (GI), (2) cell surface markers and (3) cytokine secretion profiling. While granuloma scoring showed some similarities between studies, a large variability of culture conditions and endpoints measured have been identified. The lack of any standardization currently impedes the success of a human in vitro granuloma model.
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Affiliation(s)
- Nirosha Ganesan
- Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, 3001 Leuven, Belgium; (N.G.); (J.V.)
| | - Steven Ronsmans
- Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3001 Leuven, Belgium;
| | - Jeroen Vanoirbeek
- Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, 3001 Leuven, Belgium; (N.G.); (J.V.)
- Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3001 Leuven, Belgium;
| | - Peter H. M. Hoet
- Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, 3001 Leuven, Belgium; (N.G.); (J.V.)
- Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3001 Leuven, Belgium;
- Correspondence:
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20
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Hao W, Hao C, Wu C, Xu Y, Jin C. Aluminum induced intestinal dysfunction via mechanical, immune, chemical and biological barriers. CHEMOSPHERE 2022; 288:132556. [PMID: 34648793 DOI: 10.1016/j.chemosphere.2021.132556] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 09/18/2021] [Accepted: 10/10/2021] [Indexed: 06/13/2023]
Abstract
Aluminum is the most abundant metal element in the Earth's crust, which exists naturally in the form of aluminum compounds. Aluminum is mainly absorbed through the gastrointestinal tract, which varies with different aluminum compounds. During this process, aluminum could induce the disruption of intestinal mucosa barrier. However, its underlying mechanism has not been elucidated yet. Previous studies have reported that aluminum can firstly promote the apoptosis of intestinal epithelial cells, destroy the structure of tight-junction proteins, and increase the intestinal permeability, injuring the mechanical barrier of gut. Also, it can induce the activation of immune cells to secrete inflammatory factors, and trigger immune responses, interfering with immune barrier. Moreover, aluminum treatment can regulate intestinal composition and bio-enzyme activity, impairing the function of chemical barrier. In addition, aluminum accumulation can induce an imbalance of the intestinal flora, inhibit the growth of beneficial bacteria, and promote the proliferation of harmful bacteria, which ultimately disrupting biological barrier. Collectively, aluminum may do extensive damage to intestinal barrier function covering mechanical barrier, immune barrier, chemical barrier and biological barrier.
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Affiliation(s)
- Wudi Hao
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, 110122, PR China
| | - Chenyu Hao
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, 110122, PR China
| | - Chengrong Wu
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, 110122, PR China
| | - Yuqing Xu
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, 110122, PR China
| | - Cuihong Jin
- Department of Toxicology, School of Public Health, China Medical University, Shenyang, 110122, PR China.
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21
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Food Additives, a Key Environmental Factor in the Development of IBD through Gut Dysbiosis. Microorganisms 2022; 10:microorganisms10010167. [PMID: 35056616 PMCID: PMC8780106 DOI: 10.3390/microorganisms10010167] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/04/2022] [Accepted: 01/11/2022] [Indexed: 12/12/2022] Open
Abstract
Diet is a key environmental factor in inflammatory bowel disease (IBD) and, at the same time, represents one of the most promising therapies for IBD. Our daily diet often contains food additives present in numerous processed foods and even in dietary supplements. Recently, researchers and national authorities have been paying much attention to their toxicity and effects on gut microbiota and health. This review aims to gather the latest data focusing on the potential role of food additives in the pathogenesis of IBDs through gut microbiota modulation. Some artificial emulsifiers and sweeteners can induce the dysbiosis associated with an alteration of the intestinal barrier, an activation of chronic inflammation, and abnormal immune response accelerating the onset of IBD. Even if most of these results are retrieved from in vivo and in vitro studies, many artificial food additives can represent a potential hidden driver of gut chronic inflammation through gut microbiota alterations, especially in a population with IBD predisposition. In this context, pending the confirmation of these results by large human studies, it would be advisable that IBD patients avoid the consumption of processed food containing artificial food additives and follow a personalized nutritional therapy prescribed by a clinical nutritionist.
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22
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Orsini Delgado ML, Sambuelli A, Negreira S, Gil A, D Elia L, Smaldini PL, Docena GH. Volcanic ash-driven worsening of mucosal inflammation in an experimental colitis model. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2022; 292:118351. [PMID: 34637830 DOI: 10.1016/j.envpol.2021.118351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 10/07/2021] [Accepted: 10/08/2021] [Indexed: 06/13/2023]
Abstract
Particulate matter exposure and related chemical changes in drinking water have been associated with health problems and inflammatory disorders. This study aimed to examine the effect of orally administered ash-water dilution on the gut of mice under normal and inflammatory conditions. Balb/c mice received ash-released soluble and dust-suspended components in the drinking water for 14 days. On day 7, animals were intrarectally instilled with TNBS in ethanol or flagellin from Salmonella typhimurium in PBS. At sacrifice, colon segments were collected and histologic damage, mRNA expression and cytokine levels in tissue were evaluated. In addition, these parameters were also evaluated in IL-10 null mice. We found that mice that received 5% w. fine-ash dilution in the drinking water worsened colitis signs. Weight loss, shortening of the colon, tissue edema with mucosa and submucosa cell infiltration and production of pro-inflammatory cytokines and chemokines were enhanced compared to control mice. A more pronounced inflammation was observed in IL-10 null mice. In addition, markers of NLRP3-dependent inflammasome activation were found in animals exposed to ash. In conclusion, ingestion of contaminated water with dust-suspended particulate matter enhanced the inflammatory response in the gut, probably due to alteration of the gut barrier and promoting an intense contact with the luminal content. This study critically appraises the response for fine particulate matter in uncommon illnesses reported for volcanic ash pollution. We suggest actions to enable better prediction and assessment the health impacts of volcanic eruptions.
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Affiliation(s)
- María Lucía Orsini Delgado
- Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET y Universidad Nacional de La Plata, La Plata, Argentina.
| | - Alicia Sambuelli
- Servicio de Enfermedades Inflamatorias, Hospital de Gastroenterología Bonorino Udaondo, Buenos Aires, Argentina.
| | - Silvia Negreira
- Servicio de Enfermedades Inflamatorias, Hospital de Gastroenterología Bonorino Udaondo, Buenos Aires, Argentina.
| | - Anibal Gil
- Servicio de Enfermedades Inflamatorias, Hospital de Gastroenterología Bonorino Udaondo, Buenos Aires, Argentina.
| | - Leandro D Elia
- Centro de Investigaciones Geológicas (CIG), CONICET y Universidad Nacional de La Plata, La Plata, Argentina.
| | - Paola L Smaldini
- Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET y Universidad Nacional de La Plata, La Plata, Argentina.
| | - Guillermo H Docena
- Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET y Universidad Nacional de La Plata, La Plata, Argentina.
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23
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Elevated IgG Antibody to Aluminum Bound to Human Serum Albumin in Patients with Crohn's, Celiac and Alzheimer's Disease. TOXICS 2021; 9:toxics9090212. [PMID: 34564363 PMCID: PMC8473134 DOI: 10.3390/toxics9090212] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/01/2021] [Accepted: 09/02/2021] [Indexed: 12/24/2022]
Abstract
Aluminum is in our water and food, and is used as an adjuvant in vaccines. About 40% of the ingested dose accumulates within the intestinal mucosa, making the gut the main target of inflammation and autoimmunity; about 1% accumulates in the skeletal system and brain, inducing the cross-linking of amyloid-β-42 peptide and the formation of amyloid aggregates associated with Alzheimer's disease. To examine whether the accumulation of aluminum in the gut and brain tissues results in neoantigen formation, we bound aluminum compounds to human serum albumin. We used ELISA to measure IgG antibody in 94 different sera from healthy controls and 47 sera from each group of patients: anti-Saccharomyces cerevisiae antibody-positive (Crohn's), and positive for deamidated α-gliadin and transglutaminase-2 IgA antibodies (celiac disease), autoimmune disorders associated with intestinal tissue antigens. Because earlier studies have shown that aluminum exposure is linked to Alzheimer's disease etiology, and high aluminum content is detected in Alzheimer's patients' brain tissue, we also measured aluminum antibody in the blood of these patients. Additionally, we measured aluminum antibody in the sera of mixed connective tissue disease patients who were positive for antinuclear antibodies, and used them as disease controls. We found significant IgG antibody elevation against all three aluminum compounds in the sera of patients with Crohn's, celiac and Alzheimer's disease, but not in patients with mixed connective tissue disease. We concluded that aluminum ingestion and absorption from the GI tract and brain may contribute to Crohn's, celiac and Alzheimer's disease, but not to mixed connective tissue disease.
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24
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Kostoff RN, Briggs MB, Kanduc D, Shores DR, Kovatsi L, Vardavas AI, Porter AL. Common contributing factors to COVID-19 and inflammatory bowel disease. Toxicol Rep 2021; 8:1616-1637. [PMID: 34485092 PMCID: PMC8406546 DOI: 10.1016/j.toxrep.2021.08.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 08/17/2021] [Accepted: 08/28/2021] [Indexed: 12/11/2022] Open
Abstract
The devastating complications of coronavirus disease 2019 (COVID-19) result from an individual's dysfunctional immune response following the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS-CoV-2 exploits the dysfunctional immune system to trigger a chain of events ultimately leading to COVID-19. We have previously identified many contributing factors (CFs) (representing toxic exposure, lifestyle factors and psychosocial stressors) common to myriad chronic diseases. We hypothesized significant overlap between CFs associated with COVID-19 and inflammatory bowel disease (IBD), because of the strong role immune dysfunction plays in each disease. A streamlined dot-product approach was used to identify potential CFs to COVID-19 and IBD. Of the fifty CFs to COVID-19 that were validated for demonstration purposes, approximately half had direct impact on COVID-19 (the CF and COVID-19 were mentioned in the same record; i.e., CF---→COVID-19), and the other half had indirect impact. The nascent character of the COVID-19 core literature (∼ one year old) did not allow sufficient time for the direct impacts of many CFs on COVID-19 to be identified. Therefore, an immune system dysfunction (ID) literature directly related to the COVID-19 core literature was used to augment the COVID-19 core literature and provide the remaining CFs that impacted COVID-19 indirectly (i.e., CF---→immune system dysfunction---→COVID-19). Approximately 13000 potential CFs for myriad diseases (obtained from government and university toxic substance lists) served as the starting point for the dot-product identification process. These phrases were intersected (dot-product) with phrases extracted from a PubMed-derived IBD core literature, a nascent COVID-19 core literature, and the COVID-19-related immune system dysfunction (ID) core literature to identify common ID/COVID-19 and IBD CFs. Approximately 3000 potential CFs common to both ID and IBD, almost 2300 potential CFs common to ID and COVID-19, and over 1900 potential CFs common to IBD and COVID-19 were identified. As proof of concept, we validated fifty of these ∼3000 overlapping ID/IBD candidate CFs with biologic plausibility. We further validated 24 of the fifty as common CFs in the IBD and nascent COVID-19 core literatures. This significant finding demonstrated that the CFs indirectly related to COVID-19 -- identified with use of the immune system dysfunction literature -- are strong candidates to emerge eventually as CFs directly related to COVID-19. As discussed in the main text, many more CFs common to all these core literatures could be identified and validated. ID and IBD share many common risk/contributing factors, including behaviors and toxic exposures that impair immune function. A key component to immune system health is removal of those factors that contribute to immune system dysfunction in the first place. This requires a paradigm shift from traditional Western medicine, which often focuses on treatment, rather than prevention.
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Affiliation(s)
- Ronald Neil Kostoff
- School of Public Policy, Georgia Institute of Technology, Gainesville, VA, 20155, United States
| | | | - Darja Kanduc
- Dept. of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, Via Orabona 4, Bari, 70125, Italy
| | - Darla Roye Shores
- Department of Pediatrics, Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, United States
| | - Leda Kovatsi
- Laboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, 54124, Greece
| | - Alexander I. Vardavas
- Laboratory of Toxicology & Forensic Sciences, Faculty of Medicine, University of Crete, Greece
| | - Alan L. Porter
- R&D, Search Technology, Inc., Peachtree Corners, GA, 30092, United States
- School of Public Policy, Georgia Institute of Technology, Atlanta, GA, 30332, United States
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25
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Pambianchi E, Pecorelli A, Valacchi G. Gastrointestinal tissue as a "new" target of pollution exposure. IUBMB Life 2021; 74:62-73. [PMID: 34289226 DOI: 10.1002/iub.2530] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/01/2021] [Accepted: 07/01/2021] [Indexed: 12/26/2022]
Abstract
Airborne pollution has become a leading cause of global death in industrialized cities and the exposure to environmental pollutants has been demonstrated to have adverse effects on human health. Among the pollutants, particulate matter (PM) is one of the most toxic and although its exposure has been more commonly correlated with respiratory diseases, gastrointestinal (GI) complications have also been reported as a consequence to PM exposure. Due to its composition, PM is able to exert on intestinal mucosa both direct damaging effects, (by reaching it either via direct ingestion of contaminated food and water or indirect inhalation and consequent macrophagic mucociliary clearance) and indirect ones via generation of systemic inflammation. The relationship between respiratory and GI conditions is well described by the lung-gut axis and more recently, has become even clearer during coronavirus disease 2019 (COVID-19) pandemic, when respiratory symptoms were associated with gastrointestinal conditions. This review aims at pointing out the mechanisms and the models used to evaluate PM induced GI tract damage.
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Affiliation(s)
- Erika Pambianchi
- Department of Animal Science, Plants for Human Health Institute, Kannapolis, North Carolina, USA
| | - Alessandra Pecorelli
- Department of Animal Science, Plants for Human Health Institute, Kannapolis, North Carolina, USA
| | - Giuseppe Valacchi
- Department of Animal Science, Plants for Human Health Institute, Kannapolis, North Carolina, USA.,Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy.,Department of Food and Nutrition, Kyung Hee University, Seoul, South Korea
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26
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He Z, Chen L, Catalan-Dibene J, Bongers G, Faith JJ, Suebsuwong C, DeVita RJ, Shen Z, Fox JG, Lafaille JJ, Furtado GC, Lira SA. Food colorants metabolized by commensal bacteria promote colitis in mice with dysregulated expression of interleukin-23. Cell Metab 2021; 33:1358-1371.e5. [PMID: 33989521 PMCID: PMC8266754 DOI: 10.1016/j.cmet.2021.04.015] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 02/26/2021] [Accepted: 04/20/2021] [Indexed: 12/26/2022]
Abstract
Both genetic predisposition and environmental factors appear to play a role in inflammatory bowel disease (IBD) development. Genetic studies in humans have linked the interleukin (IL)-23 signaling pathway with IBD, but the environmental factors contributing to disease have remained elusive. Here, we show that the azo dyes Red 40 and Yellow 6, the most abundant food colorants in the world, can trigger an IBD-like colitis in mice conditionally expressing IL-23, or in two additional animal models in which IL-23 expression was augmented. Increased IL-23 expression led to generation of activated CD4+ T cells that expressed interferon-γ and transferred disease to mice exposed to Red 40. Colitis induction was dependent on the commensal microbiota promoting the azo reduction of Red 40 and generation of a metabolite, 1-amino-2-naphthol-6-sulfonate sodium salt. Together these findings suggest that specific food colorants represent novel risk factors for development of colitis in mice with increased IL-23 signaling.
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Affiliation(s)
- Zhengxiang He
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Lili Chen
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
| | - Jovani Catalan-Dibene
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Gerold Bongers
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Jeremiah J Faith
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Chalada Suebsuwong
- Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Robert J DeVita
- Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Zeli Shen
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - James G Fox
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
| | - Juan J Lafaille
- Department of Pathology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
| | - Glaucia C Furtado
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Sergio A Lira
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
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27
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Zuo Y, Lu X, Wang X, Sooranna SR, Tao L, Chen S, Li H, Huang D, Nai G, Chen H, Pan C, Huang C, Pang Y. High-Dose Aluminum Exposure Further Alerts Immune Phenotype in Aplastic Anemia Patients. Biol Trace Elem Res 2021; 199:1743-1753. [PMID: 32761514 PMCID: PMC7990755 DOI: 10.1007/s12011-020-02313-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 07/29/2020] [Indexed: 11/26/2022]
Abstract
This study explored the relationship between immunological status and clinical characteristics of aplastic anemia (AA) patients to plasma aluminum levels, which were increased after constant exposure to high levels of this metal. Sixty-two AA patients (33 cases with high and 29 cases with low or no exposure to aluminum) and 30 healthy controls were selected for this study. Aluminum in human albumin solution was measured by inductivity coupled plasma mass spectrometry. IL-10, IL-12, IL-17, and INF-γ levels were measured by enzyme-linked immunosorbent assay. The distribution of lymphocyte subsets were determined by flow cytometry. The expression levels of immunoglobulins and complement C3 and C4 were also measured. Exposure to high aluminum raised the levels of serum aluminum in AA patients (P < 0.01). The levels of hemoglobin and complement C4 were lower in AA patients with high aluminum exposure (P < 0.05 and < 0.01, respectively). The percentage of CD4+ T cells and the ratio of CD4+/ CD8+T cells in peripheral blood in AA patients with high aluminum exposure were higher compared with control AA patients (P < 0.05 in both cases), while the percentage of CD8+ T cells was significantly lower than that in non-aluminum-exposed AA patients (P < 0.05). Compared with non-aluminum-exposed AA patients, the level of IL-10 in the high aluminum-exposed AA group was significantly higher (P < 0.05 in both cases). The immunological and clinical characteristics of AA patients from regions of high aluminum exposure are different to those in from non-aluminum areas. These results suggest that high aluminum exposure alters the immune system in patients suffering from AA.
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Affiliation(s)
- Yao Zuo
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
| | - Xiang Lu
- Department of Oncology, First People’s Hospital, Nanning, Guangxi China
| | - Xiaochao Wang
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
| | - Suren R. Sooranna
- Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, London, SW10 9NH UK
| | - Liju Tao
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
| | - Shiqiang Chen
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
| | - Hongwen Li
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
| | - Dan Huang
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
| | - Guanye Nai
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
| | - Hong Chen
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
| | - Chunfeng Pan
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
| | - Caihong Huang
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
| | - Yanmin Pang
- Department of Hematology, Affiliated Hospital of YouJiang Medical College for Nationalities, Baise, 533000 Guangxi China
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28
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Crawford MS, Nordgren TM, McCole DF. Every breath you take: Impacts of environmental dust exposure on intestinal barrier function-from the gut-lung axis to COVID-19. Am J Physiol Gastrointest Liver Physiol 2021; 320:G586-G600. [PMID: 33501887 PMCID: PMC8054554 DOI: 10.1152/ajpgi.00423.2020] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 01/19/2021] [Accepted: 01/20/2021] [Indexed: 01/31/2023]
Abstract
As countries continue to industrialize, major cities experience diminished air quality, whereas rural populations also experience poor air quality from sources such as agricultural operations. These exposures to environmental pollution from both rural and populated/industrialized sources have adverse effects on human health. Although respiratory diseases (e.g., asthma and chronic obstructive pulmonary disease) are the most commonly reported following long-term exposure to particulate matter and hazardous chemicals, gastrointestinal complications have also been associated with the increased risk of lung disease from inhalation of polluted air. The interconnectedness of these organ systems has offered valuable insights into the roles of the immune system and the micro/mycobiota as mediators of communication between the lung and the gut during disease states. A topical example of this relationship is provided by reports of multiple gastrointestinal symptoms in patients with coronavirus disease 2019 (COVID-19), whereas the rapid transmission and increased risk of COVID-19 has been linked to poor air quality and high levels of particulate matter. In this review, we focus on the mechanistic effects of environmental pollution on disease progression with special emphasis on the gut-lung axis.
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Affiliation(s)
- Meli'sa S Crawford
- Division of Biomedical Sciences, School of Medicine, University of California, Riverside, California
| | - Tara M Nordgren
- Division of Biomedical Sciences, School of Medicine, University of California, Riverside, California
| | - Declan F McCole
- Division of Biomedical Sciences, School of Medicine, University of California, Riverside, California
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29
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George F, Mahieux S, Daniel C, Titécat M, Beauval N, Houcke I, Neut C, Allorge D, Borges F, Jan G, Foligné B, Garat A. Assessment of Pb(II), Cd(II), and Al(III) Removal Capacity of Bacteria from Food and Gut Ecological Niches: Insights into Biodiversity to Limit Intestinal Biodisponibility of Toxic Metals. Microorganisms 2021; 9:microorganisms9020456. [PMID: 33671764 PMCID: PMC7926695 DOI: 10.3390/microorganisms9020456] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/15/2021] [Accepted: 02/18/2021] [Indexed: 12/14/2022] Open
Abstract
Toxic metals (such as lead, cadmium, and, to a lesser extent, aluminum) are detrimental to health when ingested in food or water or when inhaled. By interacting with heavy metals, gut and food-derived microbes can actively and/or passively modulate (by adsorption and/or sequestration) the bioavailability of these toxins inside the gut. This “intestinal bioremediation” involves the selection of safe microbes specifically able to immobilize metals. We used inductively coupled plasma mass spectrometry to investigate the in vitro ability of 225 bacteria to remove the potentially harmful trace elements lead, cadmium, and aluminum. Interspecies and intraspecies comparisons were performed among the Firmicutes (mostly lactic acid bacteria, including Lactobacillus spp., with some Lactococcus, Pediococcus, and Carnobacterium representatives), Actinobacteria, and Proteobacteria. The removal of a mixture of lead and cadmium was also investigated. Although the objective of the study was not to elucidate the mechanisms of heavy metal removal for each strain and each metal, we nevertheless identified promising candidate bacteria as probiotics for the intestinal bioremediation of Pb(II) and Cd(II).
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Affiliation(s)
- Fanny George
- U1286–INFINITE-Institute for Translational Research in Inflammation, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France; (F.G.); (S.M.); (M.T.); (I.H.); (C.N.)
| | - Séverine Mahieux
- U1286–INFINITE-Institute for Translational Research in Inflammation, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France; (F.G.); (S.M.); (M.T.); (I.H.); (C.N.)
| | - Catherine Daniel
- U1019-UMR 9017–Center for Infection and Immunity of Lille, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France;
| | - Marie Titécat
- U1286–INFINITE-Institute for Translational Research in Inflammation, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France; (F.G.); (S.M.); (M.T.); (I.H.); (C.N.)
| | - Nicolas Beauval
- ULR 4483-IMPECS-IMPact de l’Environnement Chimique sur la Santé humaine, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France; (N.B.); (D.A.); (A.G.)
- Unité fonctionnelle de Toxicologie, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France
| | - Isabelle Houcke
- U1286–INFINITE-Institute for Translational Research in Inflammation, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France; (F.G.); (S.M.); (M.T.); (I.H.); (C.N.)
| | - Christel Neut
- U1286–INFINITE-Institute for Translational Research in Inflammation, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France; (F.G.); (S.M.); (M.T.); (I.H.); (C.N.)
| | - Delphine Allorge
- ULR 4483-IMPECS-IMPact de l’Environnement Chimique sur la Santé humaine, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France; (N.B.); (D.A.); (A.G.)
- Unité fonctionnelle de Toxicologie, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France
| | | | - Gwénaël Jan
- STLO, INRAE, Agrocampus Ouest, Institut Agro, Science & Technologie du Lait & de l’Œuf, F-35042 Rennes, France;
| | - Benoît Foligné
- U1286–INFINITE-Institute for Translational Research in Inflammation, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France; (F.G.); (S.M.); (M.T.); (I.H.); (C.N.)
- Correspondence: ; Tel.: +33-621741015
| | - Anne Garat
- ULR 4483-IMPECS-IMPact de l’Environnement Chimique sur la Santé humaine, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France; (N.B.); (D.A.); (A.G.)
- Unité fonctionnelle de Toxicologie, Institut Pasteur de Lille, CHU Lille, Université de Lille, F-59000 Lille, France
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Rogler G, Scharl M, Spalinger M, Yilmaz B, Zaugg M, Hersberger M, Schreiner P, Biedermann L, Herfarth H. Diet and Inflammatory Bowel Disease: What Quality Standards Should Be Applied in Clinical and Laboratory Studies? Mol Nutr Food Res 2021; 65:e2000514. [PMID: 33433954 DOI: 10.1002/mnfr.202000514] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 12/21/2020] [Indexed: 12/11/2022]
Abstract
Many patients suffering from inflammatory bowel disease (IBD) follow restrictive diets, as many respective recommendations circulate. Efforts are made to evaluate and summarize the published information, for example, in a recent consensus manuscript by the International Organization for the Study of IBD (IOIBD). However, the standards that should be applied to make claims about dietary effects are poorly defined. In this manuscript, the scientific basis of recommendations for nutritional interventions in IBD is analyzed. Epidemiological evidence on diet in IBD is always biased by numerous factors, and the number of robust dietary intervention studies is limited due to methodological difficulties. Therefore, animal models are used to test hypotheses with respect to dietary factors and intestinal inflammation. Naturally, animal models have limitations, and knowledge of key characteristics of colitis animal models is crucial to understand their advantages and disadvantages. In recent years the important role of the microbiota for IBD and dietary factors has been discovered. Microbiota data are added to many publications on IBD and nutrition. The quality of those data varies largely. Subsequently, quality standards for microbiota analyses also are discussed. Finally, quality requirements to be applied on recommendations for dietary changes in patients with IBD are suggested.
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Affiliation(s)
- Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich 8091, Switzerland
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich 8091, Switzerland
| | - Marianne Spalinger
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich 8091, Switzerland
| | - Bahtiyar Yilmaz
- Maurice Müller Laboratories, Department for Biomedical Research, University Clinic of Visceral Surgery and Medicine, Inselspital, University of Bern, Bern, 3010, Switzerland
| | - Michael Zaugg
- Department of Pharmacology and Department of Anesthesiology and Pain Medicine and Cardiovascular Research Centre, University of Alberta, Edmonton, T6G 2G3, Canada
| | - Martin Hersberger
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, Zurich, 8032, Switzerland
| | - Philipp Schreiner
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich 8091, Switzerland
| | - Luc Biedermann
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich 8091, Switzerland
| | - Hans Herfarth
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, 27599-7080, USA
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31
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Hemida M, Vuori KA, Moore R, Anturaniemi J, Hielm-Björkman A. Early Life Modifiable Exposures and Their Association With Owner Reported Inflammatory Bowel Disease Symptoms in Adult Dogs. Front Vet Sci 2021; 8:552350. [PMID: 33598486 PMCID: PMC7882719 DOI: 10.3389/fvets.2021.552350] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 01/04/2021] [Indexed: 12/04/2022] Open
Abstract
Background: Inflammatory bowel disease (IBD) is an idiopathic multifactorial disease in humans and dogs, usually assigned to the interactions between genes, gut microbiota, diet, environment, and the immune system. We aimed to investigate the modifiable early life exposures associated with IBD in dogs. Materials and Methods: The study data was extracted from the validated owner-reported DogRisk food frequency questionnaire. This was a cross-sectional questionnaire-based study that tested 21 different early life dietary and environmental, demographic and genetic variables for their association with IBD or not, in adult dogs. A total of 7,015 dogs participated in this study. The study covered early life periods; prenatal, neonatal, early, and late postnatal periods. Two feeding patterns, a non-processed meat-based diet (NPMD) and an ultra-processed carbohydrate-based diet (UPCD) were studied. Data was analyzed using logistic regression analysis with a backward stepwise deletion. Results: From the final models we found that the NPMD during early and late postnatal periods were significantly associated with lower IBD risk later in life. The UPCD during the same periods was associated with a higher risk of IBD incidence. Also, the maternal diet during the neonatal period showed a non-significant trend of lower IBD risk in the offspring with the NPMD and a higher IBD risk with the UPCD. Additionally, the normal body weight of puppies during the first 6 months of age was associated with a lower risk of IBD in adulthood while, slim puppies associated significantly with IBD in adulthood. From the non-modifiable background variables, we identified the maternal history of IBD as the strongest risk factor for later incidence of IBD. Furthermore, male dogs were twice as likely to develop IBD as female dogs were. Conclusions: It is reassuring for owners to know that they themselves can have an impact on their dog's health. A high-fat, low-carbohydrate NPMD exposure during early life, and a normal body condition in puppyhood were significantly associated with less IBD in adult dogs. The opposite was true for UPCD exposure and abnormal body condition score in 6 month old puppies.
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Affiliation(s)
- Manal Hemida
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.,Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Kristiina A Vuori
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Robin Moore
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Johanna Anturaniemi
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
| | - Anna Hielm-Björkman
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
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32
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Hueso T, Ekpe K, Mayeur C, Gatse A, Joncquel-Chevallier Curt M, Gricourt G, Rodriguez C, Burdet C, Ulmann G, Neut C, Amini SE, Lepage P, Raynard B, Willekens C, Micol JB, De Botton S, Yakoub-Agha I, Gottrand F, Desseyn JL, Thomas M, Woerther PL, Seguy D. Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: the role of mucosal strengthening. Gut Microbes 2020; 12:1800897. [PMID: 32893715 PMCID: PMC7524297 DOI: 10.1080/19490976.2020.1800897] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222). In patients, we observed a decrease of plasma citrulline, which is a marker of the functional enterocyte mass, of short-chain fatty acids and of fecal bacterial load, except for Escherichia coli and Enterococcus spp., which became dominant. Both the α and β-diversities of fecal microbiota decreased. In wild-type mice, citrulline levels decreased under chemotherapy along with an increase of E. coli and Enterococcus spp load associated with concomitant histologic impairment. By comparison with wild-type mice, Tg222 mice, 3 days after completing chemotherapy, had higher citrulline levels, a faster healing epithelium, and preserved α-diversity of their intestinal microbiota. This was associated with reduced bacterial translocations. Our results highlight the intestinal damage and the dysbiosis induced by the 7 + 3 regimen. As a proof of concept, our transgenic model suggests that strengthening the intestinal barrier is a promising approach to limit BSI and improve AML patients' outcome.
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Affiliation(s)
- Thomas Hueso
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France
| | - Kenneth Ekpe
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Camille Mayeur
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Anna Gatse
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France
| | | | - Guillaume Gricourt
- NGS Platform, IMRB, CHU Henri Mondor, Créteil, France,Institut Mondor de Recherche Biomédicale, Inserm U955, Créteil, France
| | - Christophe Rodriguez
- NGS Platform, IMRB, CHU Henri Mondor, Créteil, France,Institut Mondor de Recherche Biomédicale, Inserm U955, Créteil, France
| | - Charles Burdet
- School of Medicine, EA3964 University of Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Guillaume Ulmann
- Department of Biochemistry, Cochin Hospital – HUPC, Paris, France
| | - Christel Neut
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France
| | - Salah-Eddine Amini
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France
| | - Patricia Lepage
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Bruno Raynard
- Nutrition Department, Gustave Roussy Cancer Centre, F-94805, Villejuif, France
| | - Christophe Willekens
- Hematology Departement, Gustave Roussy Cancer Centre, F-94805, Villejuif, France
| | - Jean-Baptiste Micol
- Hematology Departement, Gustave Roussy Cancer Centre, F-94805, Villejuif, France
| | - Stéphane De Botton
- Hematology Departement, Gustave Roussy Cancer Centre, F-94805, Villejuif, France
| | - Ibrahim Yakoub-Agha
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France,Allogeneic Stem Cell Department, CHU Lille, Lille, France
| | - Frédéric Gottrand
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France
| | - Jean-Luc Desseyn
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France
| | - Muriel Thomas
- Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France
| | - Paul-Louis Woerther
- Department of Microbiology and Infection Control, Henri-Mondor Hospital, Créteil, France,EA 7380 Dynamyc, EnvA, UPEC, Paris-Est University, Créteil, France
| | - David Seguy
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France,Nutrition Unit, CHU Lille, Lille, France,CONTACT David Seguy Nutrition Unit, Claude Huriez Hospital, F-59000 Lille, Lille, France
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Hu C, Liu W, Xu N, Huang A, Zhang Z, Fan M, Ruan G, Wang Y, Xi T, Xing Y. Silk fibroin hydrogel as mucosal vaccine carrier: induction of gastric CD4+TRM cells mediated by inflammatory response induces optimal immune protection against Helicobacter felis. Emerg Microbes Infect 2020; 9:2289-2302. [PMID: 33000989 PMCID: PMC7594714 DOI: 10.1080/22221751.2020.1830719] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Tissue-resident memory T (TRM) cells, located in the epithelium of most peripheral tissues, constitute the first-line defense against pathogen infections. Our previous study reported that gastric subserous layer (GSL) vaccination induced a “pool” of protective tissue-resident memory CD4+T (CD4+TRM) cells in the gastric epithelium. However, the mechanistic details how CD4+TRM cells form in the gastric epithelium are unknown. Here, our results suggested that the vaccine containing CCF in combination with Silk fibroin hydrogel (SF) broadened the distribution of gastric intraepithelial CD4+TRM cells. It was revealed that the gastric intraepithelial TRM cells were even more important than circulating memory T cells against infection by Helicobacter felis. It was also shown that gastric-infiltrating neutrophils were involved as indispensable mediators which secreted CXCL10 to chemoattract CXCR3+CD4+T cells into the gastric epithelium. Blocking of CXCR3 or neutrophils significantly decreased the number of gastric intraepithelial CD4+TRM cells due to reduced recruitment of CD4+T cells. This study demonstrated the protective efficacy of gastric CD4+TRM cells against H. felis infection, and highlighted the influence of neutrophils on gastric intraepithelial CD4+TRM cells formation.
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Affiliation(s)
- Chupeng Hu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Wei Liu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Ningyin Xu
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China
| | - An Huang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Zhenxing Zhang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Menghui Fan
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Guojing Ruan
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Yue Wang
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Tao Xi
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China
| | - Yingying Xing
- School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.,Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China
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34
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Tenailleau QM, Lanier C, Gower-Rousseau C, Cuny D, Deram A, Occelli F. Crohn's disease and environmental contamination: Current challenges and perspectives in exposure evaluation. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2020; 263:114599. [PMID: 32325248 DOI: 10.1016/j.envpol.2020.114599] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/20/2019] [Accepted: 04/13/2020] [Indexed: 06/11/2023]
Abstract
Although the incidence of Crohn's disease has increased worldwide over the past 30 years, the disorder's exact causes and physiological mechanisms have yet to be determined. Given that genetic determinants alone do not explain the development of Crohn's disease, there is growing interest in "environmental" determinants. In medical science, the term "environment" refers to both the ecological and social surroundings; however, most published studies have focused on the latter. In environmental and exposure sciences, the term "environment" mostly relates to contamination of the biotope. There are many unanswered questions on how environmental hazards might contribute to the pathogenesis of Crohn's disease. Which pollutants should be considered? Which mechanisms are involved? And how should environmental contamination and exposure be evaluated? The objective was to perform a systematic review of the literature on Crohn's disease and environmental contamination. We searched the PubMed, Google Scholar, Scopus, ISI Web of Science and Prospero databases. We considered all field studies previous to April 2019 conducted on human health indicators, and evaluating exposure to all type of physical, biological and chemical contamination of the environment. The lack of clear answers to date can be ascribed to the small total number of field studies (n = 16 of 39 publications, most of which were conducted by pioneering medical scientists), methodological differences, and the small number of contaminants evaluated. This make it impossible to conduct a coherent and efficient meta-analysis. Based on individual analysis of available studies, we formulated five recommendations on improving future research: (i) follow up the currently identified leads - especially metals and endocrine disruptors; (ii) explore soil contamination; (iii) gain a better knowledge of exposure mechanisms by developing transdisciplinary studies; (iv) identify the most plausible contaminants by developing approaches based on the source-to-target distance; and (v) develop registries and cohort-based analyses.
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Affiliation(s)
- Quentin M Tenailleau
- Univ. Lille, CHU Lille, Institut Pasteur de Lille, EA 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, F-59000, Lille, France.
| | - Caroline Lanier
- Univ. Lille, CHU Lille, Institut Pasteur de Lille, EA 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, F-59000, Lille, France
| | - Corinne Gower-Rousseau
- Public Health, Epidemiology and Economic Health Unit, EPIMAD Registry, Maison Régionale de la Recherche Clinique, University of Lille and Lille University Hospital, Lille, France; LIRIC UMR 995, Team, INSERM, University of Lille, Lille, France
| | - Damien Cuny
- Univ. Lille, CHU Lille, Institut Pasteur de Lille, EA 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, F-59000, Lille, France
| | - Annabelle Deram
- Univ. Lille, CHU Lille, Institut Pasteur de Lille, EA 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, F-59000, Lille, France
| | - Florent Occelli
- Univ. Lille, CHU Lille, Institut Pasteur de Lille, EA 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, F-59000, Lille, France
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35
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Yu L, Duan H, Kellingray L, Cen S, Tian F, Zhao J, Zhang H, Gall GL, Mayer MJ, Zhai Q, Chen W, Narbad A. Lactobacillus plantarum-Mediated Regulation of Dietary Aluminum Induces Changes in the Human Gut Microbiota: an In Vitro Colonic Fermentation Study. Probiotics Antimicrob Proteins 2020; 13:398-412. [PMID: 32712897 DOI: 10.1007/s12602-020-09677-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The gut microbiota has been identified as a target of toxic metals and a potentially crucial mediator of the bioavailability and toxicity of these metals. In this study, we show that aluminum (Al) exposure, even at low dose, affected the growth of representative strains from the human intestine via pure culture experiments. In vitro, Lactobacillus plantarum CCFM639 could bind Al on its cell surface as shown by electron microscopy and energy dispersive X-ray analysis. The potential of L. plantarum CCFM639 to reverse changes in human intestine microbiota induced by low-dose dietary Al exposure was investigated using an in vitro colonic fermentation model. Batch fermenters were inoculated with fresh stool samples from healthy adult donors and supplemented with 86 mg/L Al and/or 109 CFU of L. plantarum CCFM639. Al exposure significantly increased the relative abundances of Bacteroidetes (Prevotella), Proteobacteria (Escherichia), Actinobacteria (Collinsella), Euryarchaeota (Methanobrevibacter), and Verrucomicrobiaceae and decreased Firmicutes (Streptococcus, Roseburia, Ruminococcus, Dialister, Coprobacillus). Some changes were reversed by the inclusion of L. plantarum CCFM639. Alterations in gut microbiota induced by Al and L. plantarum CCFM639 inevitably led to changes in metabolite levels. The short-chain fatty acid (SCFAs) contents were reduced after Al exposure, but L. plantarum CCFM639 could elevate their levels. SCFAs had positive correlations with beneficial bacteria, such as Dialister, Streptococcus, Roseburia, and negative correlations with Erwinia, Escherichia, and Serratia. Therefore, dietary Al exposure altered the composition and structure of the human gut microbiota, and this was partially mitigated by L. plantarum CCFM639. This probiotic supplementation is potentially a promising and safe approach to alleviate the harmful effects of dietary Al exposure.
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Affiliation(s)
- Leilei Yu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,International Joint Research Laboratory for Probiotics at Jiangnan University, Wuxi, 214122, China
| | - Hui Duan
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Lee Kellingray
- Gut Health and Microbiome Institute Strategic Programme, Quadram Institute Bioscience, Norwich, NR4 7UQ, UK
| | - Shi Cen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China
| | - Fengwei Tian
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,International Joint Research Laboratory for Probiotics at Jiangnan University, Wuxi, 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, 214122, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, 214122, China.,(Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou, 225004, China
| | - Gwénaëlle Le Gall
- Department of Medicine, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, NR4 7TJ, UK
| | - Melinda J Mayer
- Gut Health and Microbiome Institute Strategic Programme, Quadram Institute Bioscience, Norwich, NR4 7UQ, UK
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China. .,School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China. .,International Joint Research Laboratory for Probiotics at Jiangnan University, Wuxi, 214122, China.
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.,National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, 214122, China.,Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology & Business University, Beijing, 100048, China
| | - Arjan Narbad
- International Joint Research Laboratory for Probiotics at Jiangnan University, Wuxi, 214122, China.,Gut Health and Microbiome Institute Strategic Programme, Quadram Institute Bioscience, Norwich, NR4 7UQ, UK
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36
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Jeong CH, Kwon HC, Cheng WN, Kim DH, Choi Y, Han SG. Aluminum exposure promotes the metastatic proclivity of human colorectal cancer cells through matrix metalloproteinases and the TGF-β/Smad signaling pathway. Food Chem Toxicol 2020; 141:111402. [PMID: 32437896 DOI: 10.1016/j.fct.2020.111402] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 04/30/2020] [Accepted: 04/30/2020] [Indexed: 11/15/2022]
Abstract
Human exposure to aluminum (Al) mainly occurs through food intake. However, influences of Al on the gastrointestinal tract have been rarely reported. In particular, the effect of Al on the metastasis and angiogenesis of colorectal cancer cells has not been studied. Thus, we investigated the effect of Al on the metastatic proclivity using the human colorectal cancer cell line, HT-29. Cells were exposed to 1-16 mM AlCl3 for 3-72 h. The effects of AlCl3 on HT-29 cells for migration/invasion/adhesion, and metastasis-associated protein and gene expression were evaluated. AlCl3 promoted cell migration and invasion, whereas it suppressed cell adhesion. AlCl3-exposed cells showed decreased E-cadherin and increased vimentin and Snail. AlCl3 increased transforming growth factor-beta (TGF-β) mRNA expression and Smad2/3 nuclear translocation. AlCl3-treated cells had a higher mRNA expression of matrix metalloproteinase (MMP)-7 and -9 than the control. Particularly, AlCl3-treated HT-29 cells promoted the angiogenesis of endothelial cells via increasing the secretion of vascular endothelial growth factor. Taken together, AlCl3 can promote the metastatic proclivity of colorectal cancer cells through MMP-7, -9, and TGF-β/Smad2/3 pathway. Our data suggest that Al exposure of the gastrointestinal tract may be a risk factor for metastasis initiation in colorectal cancer cells.
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Affiliation(s)
- Chang Hee Jeong
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, 05029, Republic of Korea
| | - Hyuk Cheol Kwon
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, 05029, Republic of Korea
| | - Wei Nee Cheng
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, 05029, Republic of Korea
| | - Do Hyun Kim
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, 05029, Republic of Korea
| | - Youngsok Choi
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, Republic of Korea
| | - Sung Gu Han
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, 05029, Republic of Korea.
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37
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Levine A, Rhodes JM, Lindsay JO, Abreu MT, Kamm MA, Gibson PR, Gasche C, Silverberg MS, Mahadevan U, Boneh RS, Wine E, Damas OM, Syme G, Trakman GL, Yao CK, Stockhamer S, Hammami MB, Garces LC, Rogler G, Koutroubakis IE, Ananthakrishnan AN, McKeever L, Lewis JD. Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol 2020; 18:1381-1392. [PMID: 32068150 DOI: 10.1016/j.cgh.2020.01.046] [Citation(s) in RCA: 163] [Impact Index Per Article: 32.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 12/21/2019] [Accepted: 01/24/2020] [Indexed: 02/07/2023]
Abstract
Recent evidence points to a plausible role of diet and the microbiome in the pathogenesis of both Crohn's disease (CD) and Ulcerative Colitis (UC). Dietary therapies based on exclusion of table foods and replacement with nutritional formulas and/or a combination of nutritional formulas and specific table foods may induce remission in CD. In UC, specific dietary components have also been associated with flare of disease. While evidence of varying quality has identified potential harmful or beneficial dietary components, physicians and patients at the present time do not have guidance as to which foods are safe, may be protective or deleterious for these diseases. The current document has been compiled by the nutrition cluster of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) based on the best current evidence to provide expert opinion regarding specific dietary components, food groups and food additives that may be prudent to increase or decrease in the diet of patients with inflammatory bowel diseases to control and prevent relapse of inflammatory bowel diseases.
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Affiliation(s)
- Arie Levine
- Pediatric IBD Center, Wolfson Medical Center Holon, Tel Aviv University, Tel Aviv, Israel
| | - Jonathan M Rhodes
- Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - James O Lindsay
- Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom
| | - Maria T Abreu
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Michael A Kamm
- St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Peter R Gibson
- Monash University and Alfred Health, Melbourne, Australia
| | | | - Mark S Silverberg
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Canada
| | - Uma Mahadevan
- University of California, San Francisco, San Francisco, California
| | - Rotem Sigall Boneh
- Pediatric IBD Center, Wolfson Medical Center Holon, Tel Aviv University, Tel Aviv, Israel
| | - Eyton Wine
- Department of Pediatrics, University of Alberta, Alberta, Canada; Department of Physiology, University of Alberta, Alberta, Canada
| | - Oriana M Damas
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | - Graeme Syme
- The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom
| | - Gina L Trakman
- St Vincent's Hospital and University of Melbourne, Melbourne, Australia
| | - Chu Kion Yao
- Monash University and Alfred Health, Melbourne, Australia
| | - Stefanie Stockhamer
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Canada
| | | | - Luis C Garces
- Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida
| | | | | | | | - Liam McKeever
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - James D Lewis
- Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
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Nanosized Alumina Particle and Proteasome Inhibitor Bortezomib Prevented inflammation and Osteolysis Induced by Titanium Particle via Autophagy and NF-κB Signaling. Sci Rep 2020; 10:5562. [PMID: 32221318 PMCID: PMC7101404 DOI: 10.1038/s41598-020-62254-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 03/11/2020] [Indexed: 12/17/2022] Open
Abstract
Autophagy and NF-κB signaling are involving in the process of Particle Disease, which was caused by the particles released from friction interface of artificial joint, implant materials of particle reinforced composite, scaffolds for tissue engineering, or material for drug delivery. However, the biological interaction of different material particles and the mechanism of proteasome inhibitor, Bortezomib (BTZ), against Titanium (Ti) particle-induced Particle Disease remain unclear. In this study, we evaluated effect of nanosized Alumina (Al) particles and BTZ on reducing and treating the Ti particle-induced inflammatory reaction in MG-63 cells and mouse calvarial osteolysis model. We found that Al particles and BTZ could block apoptosis and NF- κB activation in osteoblasts in vitro and in a mouse model of calvarial resorption induced by Ti particles. We found that Al particles and BTZ attenuated the expression of inflammatory cytokines (IL-1β, IL-6, TNF-α). And Al prevented the IL-1β expression induced by Ti via attenuating the NF- κB activation β-TRCP and reducing the expression of Casepase-3. Expressions of autophagy marker LC3 was activated in Ti group, and reduced by Al and/not BTZ. Furthermore, the expressions of OPG were also higher in these groups than the Ti treated group. Collectively, nanosized Al could prevent autophagy and reduce the apoptosis, inflammatory and osteolysis induced by Ti particles. Our data offered a basic data for implant design when it was inevitable to use Ti as biomaterials, considering the outstanding mechanical propertie of Ti. What's more, proteasome inhibitor BTZ could be a potential therapy for wear particle-induced inflammation and osteogenic activity via regulating the activity of NF- κB signaling pathway.
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Gu P, Feagins LA. Dining With Inflammatory Bowel Disease: A Review of the Literature on Diet in the Pathogenesis and Management of IBD. Inflamm Bowel Dis 2020; 26:181-191. [PMID: 31670372 DOI: 10.1093/ibd/izz268] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Indexed: 12/13/2022]
Abstract
Inflammatory bowel diseases (IBDs) are chronic immune-related diseases hypothesized to be a sequela of an interplay of genetic predisposition and environmental exposures. The global incidence of IBD is increasing, and more patients are exploring diet as a means to explain and treat their IBD. In fact, many patients strongly believe diet plays a fundamental role in the onset and management of their IBD. However, a significant proportion of patients report limited nutritional education from their provider, and providers report limited nutritional resources to aid in discussions with patients. This imbalance between supply and demand likely reflects the previous paucity of available literature characterizing the influence of diet in IBD. To address this gap in knowledge, we review the available literature to characterize the role of diet in the pathogenesis, exacerbation, and treatment of IBD. We aim to provide patients and providers with resources to better understand and discuss the role of diet in IBD, with the overall goal of improving patient care and satisfaction.
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Affiliation(s)
- Phillip Gu
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Linda A Feagins
- Department of Medicine, University of Texas at Austin, Dell Medical School, Austin, Texas, USA
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Guan Z, Yao G, Zeng Y, Li X. Fabrication and Characterization of In Situ Zn-TiB2 Nanocomposite. PROCEDIA MANUFACTURING 2020; 48:332-337. [PMID: 34189188 PMCID: PMC8238460 DOI: 10.1016/j.promfg.2020.05.055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Zinc (Zn) matrix composite has been newly discovered categories of biodegradable materials. With a combination of chemical stability, thermal stability and biocompatibility, ceramic nanoparticles outperformed intermetallics of zinc alloys with inherent advantages of retaining a proper corrosion rate and an exceptional ductility. Compared with Zn alloys, Zn matrix nanocomposites showed an unprecedented strengthening without sacrifices of corrosion rate, which were introduced by intermetallics. In this work, in situ titanium diboride (TiB2) reinforced Zn nanocomposite was prepared via a few cost-effective and economical methods: flux-assisted synthesis (FAS), ultrasound-assisted nanoparticle homogenization and hot rolling. 3 vol.% of TiB2 nanoparticles were synthesized with an average size of 454nm, followed by molten salt assisted ultrasound homogenization and hot rolling. Hot-rolled (HR) Zn-TiB2 performed high strength and high ductility, mostly due to precipitation strengthening (Orowan strengthening). Yield stress (YS) and ultimate tensile stress (UTS) increased by 90% and 45%, respectively, while the elongation to failure retained 23%. The mechanical performance of Zn-TiB2 made it promise to serve as an innovative biodegradable material for load-bearing applications.
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Jeong CH, Kwon HC, Kim DH, Cheng WN, Kang S, Shin DM, Yune JH, Yoon JE, Chang YH, Sohn H, Han SG. Effects of Aluminum on the Integrity of the Intestinal Epithelium: An in Vitro and in Vivo Study. ENVIRONMENTAL HEALTH PERSPECTIVES 2020; 128:17013. [PMID: 31971835 PMCID: PMC7015552 DOI: 10.1289/ehp5701] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
BACKGROUND Aluminum (Al) is the most abundant and ubiquitous metal in the environment. The main route of human exposure to Al is through food and water intake. Although human exposure to Al is common, the influence of Al on the gastrointestinal tract remains poorly understood. OBJECTIVES We aimed to further understand the toxic effect of Al and to elucidate the underlying cellular mechanisms in the intestinal barrier. METHODS The human intestinal epithelial cell line HT-29 and C57BL6 mice were exposed to AlCl3 at 0-16 mM (1-24h) and 5-50mg/kg body weight (13 weeks), respectively. In cell culture experiments, intracellular oxidative stress, inflammatory protein and gene expression, and intestinal epithelial permeability were measured. In animal studies, histological examination, gene expression, and myeloperoxidase (MPO) activity assays were conducted. RESULTS Cellular oxidative stress level (superoxide production) in AlCl3-treated cells (4 mM, 3h) was approximately 38-fold higher than that of the control. Both protein and mRNA expression of tight junction (TJ) components (occludin and claudin-1) in AlCl3-treated cells (1-4 mM, 24h) was significantly lower than that of the control. Transepithelial electrical resistance (TEER) decreased up to 67% in AlCl3-treated cells (2 mM, 24h) compared with that of the control, which decreased approximately 7%. Al activated extracellular signal-regulated kinase 1/2 and nuclear factor-kappa B (NF-κB), resulting in mRNA expression of matrix metalloproteinase-9, myosin light-chain kinase, and inflammatory cytokines [tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6] in HT-29 cells. Moreover, oral administration of AlCl3 to mice induced pathological alteration, MPO activation, and inflammatory cytokine (TNF-α, IL-1β, and IL-6) production in the colon. CONCLUSION Al induced epithelial barrier dysfunction and inflammation via generation of oxidative stress, down-regulation of the TJ proteins, and production of inflammatory cytokines in HT-29 cells. In addition, Al induced toxicity in the colon by increasing the levels of inflammatory cytokines and MPO activity and induced histological damage in a mouse model. Our data suggest that Al may be a potential risk factor for human intestinal diseases. https://doi.org/10.1289/EHP5701.
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Affiliation(s)
- Chang Hee Jeong
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea
| | - Hyuk Cheol Kwon
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea
| | - Do Hyun Kim
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea
| | - Wei Nee Cheng
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea
| | - Sukyung Kang
- Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Yonsei University, Seoul, Republic of Korea
| | - Dong-Min Shin
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea
| | - Jong Hyeok Yune
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea
| | - Jee Eun Yoon
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea
| | - You Hyun Chang
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea
| | - Hyejin Sohn
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea
| | - Sung Gu Han
- Toxicology Laboratory, Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul, Republic of Korea
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Igbokwe IO, Igwenagu E, Igbokwe NA. Aluminium toxicosis: a review of toxic actions and effects. Interdiscip Toxicol 2019; 12:45-70. [PMID: 32206026 PMCID: PMC7071840 DOI: 10.2478/intox-2019-0007] [Citation(s) in RCA: 171] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 08/29/2019] [Indexed: 12/11/2022] Open
Abstract
Aluminium (Al) is frequently accessible to animal and human populations to the extent that intoxications may occur. Intake of Al is by inhalation of aerosols or particles, ingestion of food, water and medicaments, skin contact, vaccination, dialysis and infusions. Toxic actions of Al induce oxidative stress, immunologic alterations, genotoxicity, pro-inflammatory effect, peptide denaturation or transformation, enzymatic dysfunction, metabolic derangement, amyloidogenesis, membrane perturbation, iron dyshomeostasis, apoptosis, necrosis and dysplasia. The pathological conditions associated with Al toxicosis are desquamative interstitial pneumonia, pulmonary alveolar proteinosis, granulomas, granulomatosis and fibrosis, toxic myocarditis, thrombosis and ischemic stroke, granulomatous enteritis, Crohn's disease, inflammatory bowel diseases, anemia, Alzheimer's disease, dementia, sclerosis, autism, macrophagic myofasciitis, osteomalacia, oligospermia and infertility, hepatorenal disease, breast cancer and cyst, pancreatitis, pancreatic necrosis and diabetes mellitus. The review provides a broad overview of Al toxicosis as a background for sustained investigations of the toxicology of Al compounds of public health importance.
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Affiliation(s)
- Ikechukwu Onyebuchi Igbokwe
- Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Maiduguri, Maiduguri, Nigeria
| | - Ephraim Igwenagu
- Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Maiduguri, Maiduguri, Nigeria
| | - Nanacha Afifi Igbokwe
- Department Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Maiduguri, Maiduguri, Nigeria
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Kim KH, Kim J, Han JY, Moon Y. In vitro estimation of metal-induced disturbance in chicken gut-oviduct chemokine circuit. Mol Cell Toxicol 2019; 15:443-452. [PMID: 32226460 PMCID: PMC7097086 DOI: 10.1007/s13273-019-0048-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 04/03/2019] [Indexed: 12/04/2022]
Abstract
Backgrounds Heavy metals affect various processes in the embryonic development. Embryonic fibroblasts (EFs) play key roles in the innate recognition and wound healing in reproductive tissues. Methods Based on the relative toxicities of different inorganic metals and inorganic nonmetallic compounds against murine and chicken EF cells, mechanistic estimations were performed based on transcriptomic analyses. Results Lead (II) acetate induced preferential injuries in the chicken EF and mechanistic analyses using transcriptome revealed that chemokine receptor-associated events are potently involved in metal-induced adverse actions. As an early sentinel of metal exposure, the precision-cut intestine slices (PCIS) induced the expression of chemokines including CXCLi1 or CXCLi2, which were potent gut-derived factors that activate chemokine receptors in reproductive organs after circulation. Conclusion EF-selective metals can be estimated to trigger the chemokine circuit in the gut-reproductive axis of chickens. This in vitro methodology using PCIS-EF culture could be used as a promising alternate platform for the reproductive immunotoxicological assessment.
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Affiliation(s)
- Ki Hyung Kim
- 1Department of Biomedical Sciences, Biomedical Research Institute, Pusan National University, Yangsan, 50612 Republic of Korea.,2Biomedical Research Institute and Pusan Cancer Center, Busan National University Hospital, Busan, Republic of Korea.,3Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Juil Kim
- 1Department of Biomedical Sciences, Biomedical Research Institute, Pusan National University, Yangsan, 50612 Republic of Korea
| | - Jae Yong Han
- 4Department of Agricultural Biotechnology, Seoul National University, Seoul, 08826 Republic of Korea
| | - Yuseok Moon
- 1Department of Biomedical Sciences, Biomedical Research Institute, Pusan National University, Yangsan, 50612 Republic of Korea.,2Biomedical Research Institute and Pusan Cancer Center, Busan National University Hospital, Busan, Republic of Korea.,College of Information and Biomedical Engineering, Yangsan, 50612 Republic of Korea
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Schmitt H, Neufert C, Neurath MF, Atreya R. Resolution of Crohn's disease. Semin Immunopathol 2019; 41:737-746. [PMID: 31552470 DOI: 10.1007/s00281-019-00756-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 09/05/2019] [Indexed: 12/19/2022]
Abstract
Crohn's disease (CD) is characterized by chronic inflammation of the gastrointestinal tract and represents one of the main inflammatory bowel disease (IBD) forms. The infiltration of immune cells into the mucosa and uncontrolled production of pro-inflammatory cytokines and other mediators trigger the chronic inflammatory reaction in the intestine [1]. The inflammatory setting consists of subsequent events that comprise an induction phase, the peak of inflammation which is subsequently followed by the resolution phase. The induction phase, which represents the first phase of inflammation, is important for the rapid and efficient activation of the immune system for sufficient host defense. The permanent sensing of exogenous or endogenous danger signals enables the fast initiation of the inflammatory reaction. The immune cell infiltrate initiates an inflammatory cascade where released lipid and protein mediators play an indispensable role [2, 3]. The last decades of research strongly suggest that resolution of inflammation is similarly a tightly coordinated and active process. The basic concept that resolution of inflammation has to be regarded as an active process has been thoroughly described by others [4-6]. The following review focuses on mechanisms, pathways, and specific mediators that are actively involved in the resolution of inflammation in CD.
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Affiliation(s)
- Heike Schmitt
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Clemens Neufert
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Markus F Neurath
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Ulmenweg 18, 91054, Erlangen, Germany
| | - Raja Atreya
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Ulmenweg 18, 91054, Erlangen, Germany.
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Yu L, Wu J, Zhai Q, Tian F, Zhao J, Zhang H, Chen W. Metabolomic analysis reveals the mechanism of aluminum cytotoxicity in HT-29 cells. PeerJ 2019; 7:e7524. [PMID: 31523502 PMCID: PMC6716502 DOI: 10.7717/peerj.7524] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 07/21/2019] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Aluminum (Al) is toxic to animals and humans. The most common sources of human exposure to Al are food and beverages. The intestinal epithelium is the first barrier against Al-induced toxicity. In this study, HT-29, a human colon cancer cell line, was selected as an in vitro model to evaluate the Al-induced alteration in metabolomic profiles and explore the possible mechanisms of Al toxicity. METHODS MTT assay was performed to determine the half-maximal inhibitory concentration of Al ions. Liquid chromatography-mass spectrometry (LC-MS) was used for metabolomic analysis, and its results were further confirmed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) of nine selected genes. RESULTS Al inhibited the growth of the HT-29 cells, and its half-maximal dose for the inhibition of cell proliferation was found to be four mM. This dose was selected for further metabolomic analysis, which revealed that 81 metabolites, such glutathione (GSH), phosphatidylcholines, phosphatidylethanolamines, and creatine, and 17 metabolic pathways, such as the tricarboxylic acid cycle, pyruvate metabolism, and GSH metabolism, were significantly altered after Al exposure. The RT-qPCR results further confirmed these findings. CONCLUSION The metabolomics and RT-qPCR results indicate that the mechanisms of Al-induced cytotoxicity in HT-29 cells include cellular apoptosis, oxidative stress, and alteration of lipid, energy, and amino acid metabolism.
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Affiliation(s)
- Leilei Yu
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi, China
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Jiangping Wu
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Qixiao Zhai
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi, China
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Fengwei Tian
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi, China
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Jianxin Zhao
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou, China
| | - Hao Zhang
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China
| | - Wei Chen
- School of Food Science and Technology, Jiangnan University, Wuxi, China
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China
- Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology & Business University, Wuxi, China
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Inflammatory Bowel Diseases and Food Additives: To Add Fuel on the Flames! Nutrients 2019; 11:nu11051111. [PMID: 31109097 PMCID: PMC6567822 DOI: 10.3390/nu11051111] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 05/15/2019] [Accepted: 05/16/2019] [Indexed: 12/16/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) develop in genetically predisposed individuals in response to environmental factors. IBDs are concomitant conditions of industrialized societies, and diet is a potential culprit. Consumption of ultra-processed food has increased over the last decade in industrialized countries, and epidemiological studies have found associations between ultra-processed food consumption and chronic diseases. Further studies are now required to identify the potential culprit in ultra-processed food, such as a poor nutritional composition or the presence of food additives. In our review, we will focus on food additives, i.e., substances from packaging in contact with food, and compounds formed during production, processing, and storage. A literature search using PubMed from inception to January 2019 was performed to identify relevant studies on diet and/or food additive and their role in IBDs. Manuscripts published in English from basic science, epidemiological studies, or clinical trials were selected and reviewed. We found numerous experimental studies highlighting the key role of food additives in IBD exacerbation but epidemiological studies on food additives on IBD risk are still limited. As diet is a modifiable environmental risk factor, this may offer a scientific rationale for providing dietary advice for IBD patients.
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Liu J, Gu Z, Zhang H, Zhao J, Chen W. Preventive effects of Lactobacillus plantarum ST-III against Salmonella infection. Lebensm Wiss Technol 2019. [DOI: 10.1016/j.lwt.2019.02.043] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Li M, Cui ZG, Zakki SA, Feng Q, Sun L, Feril LB, Inadera H. Aluminum chloride causes 5-fluorouracil resistance in hepatocellular carcinoma HepG2 cells. J Cell Physiol 2019; 234:20249-20265. [PMID: 30993729 DOI: 10.1002/jcp.28625] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 03/18/2019] [Accepted: 03/19/2019] [Indexed: 01/18/2023]
Abstract
Chemoresistance is one of the major obstacles in chemotherapy-based hepatocellular carcinoma (HCC) intervention. Aluminum (Al) is an environmental pollutant that plays a vital role in carcinogenesis, tumorigenesis, and metastasis. However, the effect of Al on chemoresistance remains unknown. 5-Fluorouracil (5-FU) is a widely used antitumor drug. Therefore, we investigated the effects of aluminum chloride (AlCl3 ) on the chemoresistance of HepG2 cells to 5-FU and explored the underlying mechanisms of these effects. The results demonstrated that AlCl3 pretreatment attenuated 5-FU-induced apoptosis through Erk activation and reversed 5-FU-induced cell cycle arrest by downregulating p-Chk2Thr68 levels. In addition, AlCl3 markedly increased the levels of proteins associated with cell migration, such as MMP-2 and MMP-9. Further investigation demonstrated that an Erk inhibitor (U0126) reversed the AlCl3 -induced decrease in apoptosis, enhancement of cell cycle progression, promotion of cell migration, and attenuation of oxidative stress. In summary, AlCl3 induced chemoresistance to 5-FU in HepG2 cells. The present study suggests a potential influence of AlCl3 on 5-FU therapy. These findings may help others to understand and properly address the resistance of HCC to chemotherapeutic agents.
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Affiliation(s)
- Mengling Li
- Department of Public Health, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
| | - Zheng-Guo Cui
- Department of Public Health, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan.,Graduate School of Medicine, Henan Polytechnic University, Jiaozuo, China
| | - Shahbaz Ahmad Zakki
- Department of Public Health, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
| | - Qianwen Feng
- Department of Public Health, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
| | - Lu Sun
- Department of Public Health, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
| | - Loreto B Feril
- Department of Anatomy, Fukuoka University School of Medicine, Fukuoka, Japan
| | - Hidekuni Inadera
- Department of Public Health, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
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Radan M, Dianat M, Badavi M, Mard SA, Bayati V, Goudarzi G. In vivo and in vitro evidence for the involvement of Nrf2-antioxidant response element signaling pathway in the inflammation and oxidative stress induced by particulate matter (PM10): the effective role of gallic acid. Free Radic Res 2019; 53:210-225. [PMID: 30585515 DOI: 10.1080/10715762.2018.1563689] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Environmental pollution is one of the risk factors for respiratory diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is the major mechanisms contributing to cellular defense against oxidative damage. Gallic acid (GA) is regarded as potent anti-inflammatory and antioxidant agents. The aim was to evaluate the role of Nrf2 pathway in particulate matter (PM10) exposure on lung and epithelial cells with an emphasis on the role of GA. In in vivo part, the rats were divided as control, GA (30 mg/kg), particulate matter (PM) (0.5, 2.5, and 5 mg/kg), and PM + GA. In in vitro study, the cells were divided as control, PM10 (100, 250, and 500 µg/ml), GA (50 µmol/L) and PM10+GA. Inflammation, oxidative stress and Nrf2-pathway factors were assessed. PM10 groups showed a considerable increase in the epithelial permeability and inflammatory parameters. We also found a significant decrease in the expression of Nrf2 and its up-stream regulators genes. Accordingly, the biosynthesis of glutathione (GSH) and other antioxidant activities significantly decreased. Gallic acid was identified to restore the antioxidant status to the normal levels. Our findings approved that Nrf2 is involved in PM10-induced oxidative damages and showed that Nrf2 activation by natural agents could ameliorate respiratory injuries induced by PM10.
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Affiliation(s)
- Maryam Radan
- a Faculty of Medicine, Department of Physiology , Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
| | - Mahin Dianat
- a Faculty of Medicine, Department of Physiology , Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
| | - Mohammad Badavi
- a Faculty of Medicine, Department of Physiology , Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
| | - Seyyed Ali Mard
- a Faculty of Medicine, Department of Physiology , Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
| | - Vahid Bayati
- b Faculty of Medicine , Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
| | - Gholamreza Goudarzi
- c Health Faculty, Department of Environmental Health Engineering , Ahvaz Jundishapur University of Medical Sciences , Ahvaz , Iran
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Kikut J, Konecka N, Ziętek M, Szczuko M. Inflammatory Bowel Disease Etiology: Current Knowledge. Pteridines 2018. [DOI: 10.1515/pteridines-2018-0020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Abstract
Non-specific inflammatory bowel diseases (IBD) include Crohn’s disease (CD) and ulcerative colitis (UC). Both diseases are characterized by chronic inflammation of unclear etiology. The inflammatory bowel diseases incidence is continuously observed to rise. Colon inflammatory response is a physiological process which occurrence is indispensable as an organisms’ defense reaction. The inflammation may be caused by internal factors associated with body’s cells as well as external factors, such as infections and exposition for inflammatory agents. Until recently, IBD have been classified as autoimmune diseases, today they seem to be associated with gut barrier disorders or dysbiosis. Factors that predispose to inflammatory bowel diseases include: genetic factors, dysbiosis and so called western-type diet, natural components such as gluten and lactose. In addition, the development of the disease is favored by: cigarette smoking, phosphate, nanomolecules, sodium chloride, emulgents, carrageenan, carboxymethylcellulose, pollution, maltodextrin. IBD affects whole the body, causing serious medical consequences. Symptoms like anxiety and chronic stress, that occur commonly, can lead to depressive disorders. Quantitative and qualitative dietary deficiency caused by absorption disorders, may promote the occurrence of osteoporosis and osteopenia. In addition, dysbiosis coexisting with alterations in intestinal permeability can lead to the development of nonalcoholic fatty liver disease. IBD medical consequences include also systemic complications, associated with the extra gastrointestinal manifestations’ occurrence.
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Affiliation(s)
- Justyna Kikut
- Department of Biochemistry and Human Nutrition, Pomeranian Medical University in Szczecin , Poland
| | - Nina Konecka
- Department of Applied Neurocognitivistic, Pomeranian Medical University in Szczecin , Poland
| | - Maciej Ziętek
- Department of Perinatology, Obstetrics and Gynecology Pomeranian Medical University in Szczecin , Poland
| | - Małgorzata Szczuko
- Departament of Biochemistry and Human Nutrition, Pomeranian Medical University in Szczecin , Poland
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