1
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Bai S, Lu J, Hua L, Liu Q, Chen M, Gu Y, Zhang J, Ma D, Bao Y. Prediction of asthma using a four-locus gene model including IL13, IL4, FCER1B, and ADRB2 in children of Kazak nationality. Ital J Pediatr 2023; 49:162. [PMID: 38049812 PMCID: PMC10694882 DOI: 10.1186/s13052-023-01564-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 11/21/2023] [Indexed: 12/06/2023] Open
Abstract
BACKGROUND To study whether the four locus gene model consisting of ADRB2 rs1042713, IL4 rs2243250, FCER1B rs569108 and L13 rs20541 can predict asthma of the Kazak children in Xinjiang, China. METHODS Four single nucleotide polymorphisms about the 4 genes were genotyped in asthma group and control group of Han children and Kazak children respectively. The frequencies of different genotypes and alleles were compared between the asthma group and the control group in the two nationalities. Different risk genotypes for asthma were evaluated in the two nationalities. RESULTS The differences about frequencies of genotypes in ADRB2 rs1042713 and IL4 rs2243250 and IL13 rs20541 between asthma group and control group were statistically significant in Han children, as were the frequencies of alleles in the 3 single nucleotide polymorphisms, but there were no statistical differences in FCER1B rs569108(P > 0.05). For the Kazak children, no differences were existed among all the genotypes and alleles in asthma group and control group. For the Han children, more children were asthma high risk genotype in the asthma group than those in the control group and no difference was found in the Kazak children. CONCLUSIONS The four locus gene model consisting of ADRB2 rs1042713, IL4 rs2243250, FCER1B rs569108 and L13 rs20541 can predict asthma of Han children but not for the Kazak children in Xinjiang, which illustrating that the difference of asthma prevalence between different races is closely related to the genetic background.
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Affiliation(s)
- Shasha Bai
- Department of Pediatric Pulmonology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Lu
- Children's Respiratory Diagnosis and Treatment Center, Urumqi First People's Hospital, Xinjiang, China
| | - Li Hua
- Department of Pediatric Pulmonology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Quanhua Liu
- Department of Pediatric Pulmonology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengxue Chen
- Department of Pediatric Pulmonology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yutong Gu
- Department of Pediatric Pulmonology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianhua Zhang
- Department of Pediatric Pulmonology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dongjun Ma
- Children's Respiratory Diagnosis and Treatment Center, Urumqi First People's Hospital, Xinjiang, China
| | - Yixiao Bao
- Department of Pediatric Pulmonology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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2
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Taleb NN, West J. Working with Convex Responses: Antifragility from Finance to Oncology. ENTROPY (BASEL, SWITZERLAND) 2023; 25:343. [PMID: 36832709 PMCID: PMC9955868 DOI: 10.3390/e25020343] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 01/23/2023] [Accepted: 01/25/2023] [Indexed: 06/07/2023]
Abstract
We extend techniques and learnings about the stochastic properties of nonlinear responses from finance to medicine, particularly oncology, where it can inform dosing and intervention. We define antifragility. We propose uses of risk analysis for medical problems, through the properties of nonlinear responses (convex or concave). We (1) link the convexity/concavity of the dose-response function to the statistical properties of the results; (2) define "antifragility" as a mathematical property for local beneficial convex responses and the generalization of "fragility" as its opposite, locally concave in the tails of the statistical distribution; (3) propose mathematically tractable relations between dosage, severity of conditions, and iatrogenics. In short, we propose a framework to integrate the necessary consequences of nonlinearities in evidence-based oncology and more general clinical risk management.
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Affiliation(s)
| | - Jeffrey West
- Integrated Mathematical Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA
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3
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Petersen AM. Gastrointestinal dysbiosis and Escherichia coli pathobionts in inflammatory bowel diseases. APMIS 2022; 130 Suppl 144:1-38. [PMID: 35899316 PMCID: PMC9546507 DOI: 10.1111/apm.13256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Andreas Munk Petersen
- Department of Gastroenterology and Department of Clinical Microbiology, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark
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4
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Sanchez K, Darling JS, Kakkar R, Wu SL, Zentay A, Lowry CA, Fonken LK. Mycobacterium vaccae immunization in rats ameliorates features of age-associated microglia activation in the amygdala and hippocampus. Sci Rep 2022; 12:2165. [PMID: 35140249 PMCID: PMC8828872 DOI: 10.1038/s41598-022-05275-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 01/05/2022] [Indexed: 12/14/2022] Open
Abstract
Aging and reduced exposure to environmental microbes can both potentiate neuroinflammatory responses. Prior studies indicate that immunization with the immunoregulatory and anti-inflammatory bacterium, Mycobacterium vaccae (M. vaccae), in aged rats limits neuroimmune activation and cognitive impairments. However, the mechanisms by which M. vaccae immunization ameliorates age-associated neuroinflammatory “priming” and whether microglia are a primary target remain unclear. Here, we investigated whether M. vaccae immunization protects against microglia morphological changes in response to aging. Adult (3 mos) and aged (24 mos) Fisher 344 × Brown Norway rats were immunized with either M. vaccae or vehicle once every week for 3 weeks. Aging led to elevated Iba1 immunoreactivity, microglial density, and deramification of microglia processes in the hippocampus and amygdala but not other brain regions. Additionally, aged rats exhibited larger microglial somas in the dorsal hippocampus, suggestive of a more activated phenotype. Notably, M. vaccae treatment ameliorated indicators of microglia activation in both the amygdala and hippocampus. While changes in morphology appeared to be region-specific, gene markers indicative of microglia activation were upregulated by age and lowered in response to M. vaccae in all brain regions evaluated. Taken together, these data suggest that peripheral immunization with M. vaccae quells markers of age-associated microglia activation.
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Affiliation(s)
- Kevin Sanchez
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 107 W Dean Keeton St 3.510C, Austin, TX, 78712, USA
| | - Jeffrey S Darling
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 107 W Dean Keeton St 3.510C, Austin, TX, 78712, USA
| | - Reha Kakkar
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 107 W Dean Keeton St 3.510C, Austin, TX, 78712, USA
| | - Sienna L Wu
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 107 W Dean Keeton St 3.510C, Austin, TX, 78712, USA
| | - Andrew Zentay
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 107 W Dean Keeton St 3.510C, Austin, TX, 78712, USA
| | - Christopher A Lowry
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, 80309, USA.,Center for Neuroscience, University of Colorado Boulder, Boulder, CO, 80309, USA
| | - Laura K Fonken
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, 107 W Dean Keeton St 3.510C, Austin, TX, 78712, USA.
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5
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Finlay BB, Amato KR, Azad M, Blaser MJ, Bosch TCG, Chu H, Dominguez-Bello MG, Ehrlich SD, Elinav E, Geva-Zatorsky N, Gros P, Guillemin K, Keck F, Korem T, McFall-Ngai MJ, Melby MK, Nichter M, Pettersson S, Poinar H, Rees T, Tropini C, Zhao L, Giles-Vernick T. The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome. Proc Natl Acad Sci U S A 2021; 118:e2010217118. [PMID: 33472859 PMCID: PMC8017729 DOI: 10.1073/pnas.2010217118] [Citation(s) in RCA: 95] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Indexed: 12/12/2022] Open
Abstract
The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with preexisting conditions, such as diabetes and obesity, which are also associated with microbiome abnormalities. Current pandemic control measures and practices will have broad, uneven, and potentially long-term effects for the human microbiome across the planet, given the implementation of physical separation, extensive hygiene, travel barriers, and other measures that influence overall microbial loss and inability for reinoculation. Although much remains uncertain or unknown about the virus and its consequences, implementing pandemic control practices could significantly affect the microbiome. In this Perspective, we explore many facets of COVID-19-induced societal changes and their possible effects on the microbiome, and discuss current and future challenges regarding the interplay between this pandemic and the microbiome. Recent recognition of the microbiome's influence on human health makes it critical to consider both how the microbiome, shaped by biosocial processes, affects susceptibility to the coronavirus and, conversely, how COVID-19 disease and prevention measures may affect the microbiome. This knowledge may prove key in prevention and treatment, and long-term biological and social outcomes of this pandemic.
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Affiliation(s)
- B Brett Finlay
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada;
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
| | - Katherine R Amato
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Anthropology, Northwestern University, Evanston, IL 60208
| | - Meghan Azad
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Manitoba Interdisciplinary Lactation Centre, Children's Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Martin J Blaser
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Center for Advanced Biotechnology and Medicine at Rutgers Biomedical and Health Sciences, Rutgers University, Piscataway, NJ 08854-8021
| | - Thomas C G Bosch
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Zoologisches Institut, University of Kiel, 24118 Kiel, Germany
| | - Hiutung Chu
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Pathology, University of California San Diego, La Jolla, CA 92093
| | - Maria Gloria Dominguez-Bello
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ 08901
| | - Stanislav Dusko Ehrlich
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Metagenopolis Unit, French National Institute for Agricultural Research, 78350 Jouy-en-Josas, France
| | - Eran Elinav
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Immunology, Weizmann Institute of Science, Rehovot 761000, Israel
- Cancer-Microbiome Division, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany
| | - Naama Geva-Zatorsky
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Technion Integrated Cancer Center, Department of Cell Biology and Cancer Science, Technion-Israel Institute of Technology, Haifa 3525433, Israel
| | - Philippe Gros
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada
| | - Karen Guillemin
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Institute of Molecular Biology, University of Oregon, Eugene, OR 97403
| | - Frédéric Keck
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Centre National de la Recherche Scientifique, 75016 Paris, France
- Laboratoire d'Anthropologie Sociale, Collège de France, 75005 Paris, France
| | - Tal Korem
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Systems Biology, Irving Cancer Research Center, Columbia University, New York, NY 10032
- Department of Obstetrics and Gynecology, Irving Cancer Research Center, Columbia University, New York, NY 10032
| | - Margaret J McFall-Ngai
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Pacific Biosciences Research Center, University of Hawai'i at Manoa, Honolulu, HI 96822
| | - Melissa K Melby
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Anthropology, University of Delaware, Newark, DE 19711
| | - Mark Nichter
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Anthropology, University of Arizona, Tucson, AZ 85721
| | - Sven Pettersson
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Lee Kong Chian School of Medicine, Nanyang Technological University, 637715 Singapore
| | - Hendrik Poinar
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Anthropology, McMaster University, Hamilton, ON L8S 4M4, Canada
| | - Tobias Rees
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Transformations of the Human Program, Berggruen Institute, Los Angeles, CA 90013
| | - Carolina Tropini
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
- Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
| | - Liping Zhao
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ 08901
| | - Tamara Giles-Vernick
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada;
- Anthropology & Ecology of Disease Emergence, Institut Pasteur, 75015 Paris, France
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6
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Liao J, Zhang B, Xia W, Cao Z, Zhang Y, Liang S, Hu K, Xu S, Li Y. Residential exposure to green space and early childhood neurodevelopment. ENVIRONMENT INTERNATIONAL 2019; 128:70-76. [PMID: 31029981 DOI: 10.1016/j.envint.2019.03.070] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 02/22/2019] [Accepted: 03/28/2019] [Indexed: 06/09/2023]
Abstract
BACKGROUND A few studies reported that exposure to high levels of residential surrounding green spaces was associated with better cognitive development in primary school children. However, no studies have been conducted to examine such association in early childhood. OBJECTIVES We investigated the association between residential exposure to green space and early childhood neurodevelopment, and further explored the mediation effects of traffic-related air pollution and maternal physical activity on this association. METHODS We enrolled 1312 pregnant women between January 2012 and October 2015 and their children were followed up until an age of 2 years. We measured residential exposure to green space by calculating averaged normalized difference vegetation index (NDVI) within a 300 meter buffer area surrounding residential address at birth. The neurodevelopment, which included mental development index (MDI) and psychomotor development index (PDI), was assessed using Bayley Scales of Infant Development for each child at about 24 months. The associations of residential exposure to NDVI with early childhood MDI score and PDI score were evaluated using multiple linear regression models. The mediation effects of traffic-related air pollution and maternal physical activities on those associations were estimated by causal mediation analyses. RESULTS Exposure to higher levels of residential surrounding green spaces was associated with increased early childhood PDI score (adjusted changes for one SD increment of NDVI: 3.28 (95% CI: 2.15, 4.41)) and MDI score (adjusted changes for one SD increment of NDVI: 1.97 (95% CI: 0.63, 3.30). These associations were more pronounced in children of mothers whose pre-pregnancy BMI were lower than 24 kg/m2. Further mediation analyses indicated that reduced levels of traffic-related air pollution explained 13.6% to 28.0% of the association between exposure to green space and early childhood PDI score. CONCLUSION Exposure to higher levels of residential surrounding green spaces was associated with better early childhood neurodevelopment. The association between exposure to green space and early childhood psychomotor development might be partly explained by reduced levels of traffic-related air pollution.
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Affiliation(s)
- Jiaqiang Liao
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Bin Zhang
- Women and Children Medical and Healthcare Center of Wuhan, Wuhan, Hubei, People's Republic of China
| | - Wei Xia
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Zhongqiang Cao
- Women and Children Medical and Healthcare Center of Wuhan, Wuhan, Hubei, People's Republic of China
| | - Yimin Zhang
- Women and Children Medical and Healthcare Center of Wuhan, Wuhan, Hubei, People's Republic of China
| | - Shengwen Liang
- Wuhan Environmental Monitoring Center, Wuhan, Hubei Province 430000, China
| | - Ke Hu
- Wuhan Environmental Monitoring Center, Wuhan, Hubei Province 430000, China
| | - Shunqing Xu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Yuanyuan Li
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
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7
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Fox M, Knorr DA, Haptonstall KM. Alzheimer's disease and symbiotic microbiota: an evolutionary medicine perspective. Ann N Y Acad Sci 2019; 1449:3-24. [PMID: 31180143 DOI: 10.1111/nyas.14129] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 04/19/2019] [Accepted: 05/03/2019] [Indexed: 12/15/2022]
Abstract
Microorganisms resident in our bodies participate in a variety of regulatory and pathogenic processes. Here, we describe how etiological pathways implicated in Alzheimer's disease (AD) may be regulated or disturbed by symbiotic microbial activity. Furthermore, the composition of symbiotic microbes has changed dramatically across human history alongside the rise of agriculturalism, industrialization, and globalization. We postulate that each of these lifestyle transitions engendered progressive depletion of microbial diversity and enhancement of virulence, thereby enhancing AD risk pathways. It is likely that the human life span extended into the eighth decade tens of thousands of years ago, yet little is known about premodern geriatric epidemiology. We propose that microbiota of the gut, oral cavity, nasal cavity, and brain may modulate AD pathogenesis, and that changes in the microbial composition of these body regions across history suggest escalation of AD risk. Dysbiosis may promote immunoregulatory dysfunction due to inadequate education of the immune system, chronic inflammation, and epithelial barrier permeability. Subsequently, proinflammatory agents-and occasionally microbes-may infiltrate the brain and promote AD pathogenic processes. APOE genotypes appear to moderate the effect of dysbiosis on AD risk. Elucidating the effect of symbiotic microbiota on AD pathogenesis could contribute to basic and translational research.
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Affiliation(s)
- Molly Fox
- Department of Anthropology, University of California Los Angeles, Los Angeles, California.,Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California
| | - Delaney A Knorr
- Department of Anthropology, University of California Los Angeles, Los Angeles, California
| | - Kacey M Haptonstall
- Department of Ecology and Evolutionary Biology, University of California Los Angeles, Los Angeles, California
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8
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da Silva TM, Fiaccone RL, Kehdy FSG, Tarazona-Santos E, Rodrigues LC, Costa GNO, Figueiredo CA, Dos Santos DN, Feitosa CA, Fattore GL, Santos LM, Alcantara-Neves NM, Cruz ÁA, Barreto ML. African biogeographical ancestry, atopic and non-atopic asthma and atopy: A study in Latin American children. Pediatr Pulmonol 2019; 54:125-132. [PMID: 30548437 DOI: 10.1002/ppul.24213] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 11/03/2018] [Indexed: 11/06/2022]
Abstract
BACKGROUND Genetic variants underlying African ancestry have been suggested be implicated in the ethnic-racial inequalities reported for asthma and allergies. OBJECTIVES To investigate the association between individual African ancestry and asthma symptoms, atopic and non-atopic asthma, and atopy in children. METHODS A cross-sectional study encompassing 1190 individuals was conducted. African biogeographic ancestry was estimated using 370 539 genome-wide SNPs. Serum levels of specific IgE were measured, and skin prick test (SPT) performed for the most common local aeroallergens. Information on asthma symptoms was obtained by applying the International Study of Allergy and Asthma in Childhood questionnaire. The associations between the proportion of individual African ancestry and the outcomes investigated were analyzed through multivariate models adjusted for socio-environmental variables, infections markers, and psychosocial factors. RESULTS Each 20% increase in the proportion of African ancestry was negatively associated with SPT reactivity (OR: 0.79, 95%CI: 0.66-0.96) and positively associated with asthma symptoms in non-atopic individuals (OR: 1.40, 95%CI: 1.03-1.89). We estimated that socioeconomic status and number of infections mediated 28.4% of the effect of African ancestry on SPT reactivity, while 20.2% of the effect on non-atopic asthma was explained by socioeconomic status and behavioral problems in children. CONCLUSIONS The negative association observed between African ancestry and atopy is most probably explained by unobserved environmental or social factors that covariate with ancestry. For non-atopic asthma, in turn, putative genetic variants of risk underlying African ancestry may play some role.
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Affiliation(s)
- Thiago M da Silva
- Institute of Collective Health, Federal University of Bahia, Salvador, Bahia, Brazil.,Departamento de Ciências Biológicas, Universidade Estadual do Sudoeste da Bahia, Jequié, Bahia, Brazil
| | - Rosemeire L Fiaccone
- Departamento de Estatística, Instituto de Matemática, Universidade Federal da Bahia, Salvador, Bahia, Brazil.,Center of Data and Knowledge Integration for Health, Instituto Gonçalo Muniz, Fundação Osvaldo Cruz, Salvador, Brazil
| | - Fernanda S G Kehdy
- Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de, Janeiro, Brazil
| | - Eduardo Tarazona-Santos
- Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Laura C Rodrigues
- Department of Infectious Disease Epidemiology, Faculty of Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Gustavo N O Costa
- Institute of Collective Health, Federal University of Bahia, Salvador, Bahia, Brazil.,Center of Data and Knowledge Integration for Health, Instituto Gonçalo Muniz, Fundação Osvaldo Cruz, Salvador, Brazil
| | - Camila A Figueiredo
- Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil
| | - Darci N Dos Santos
- Institute of Collective Health, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Caroline A Feitosa
- Institute of Collective Health, Federal University of Bahia, Salvador, Bahia, Brazil
| | - Gisel L Fattore
- Institute of Collective Health, Federal University of Bahia, Salvador, Bahia, Brazil.,Departamento de Salud Comunitaria, Universidad Nacional de Lanús, Buenos Aires, Argentina
| | - Leticia M Santos
- Institute of Collective Health, Federal University of Bahia, Salvador, Bahia, Brazil
| | | | - Álvaro A Cruz
- ProAR-Center of Excellence in Asthma, Federal University of Bahia School of Medicine, Salvador, Brazil
| | - Maurício L Barreto
- Institute of Collective Health, Federal University of Bahia, Salvador, Bahia, Brazil.,Center of Data and Knowledge Integration for Health, Instituto Gonçalo Muniz, Fundação Osvaldo Cruz, Salvador, Brazil
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9
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Mirjalali H, Abbasi MR, Naderi N, Hasani Z, Mirsamadi ES, Stensvold CR, Balaii H, Asadzadeh Aghdaei H, Zali MR. Distribution and phylogenetic analysis of Blastocystis sp. subtypes isolated from IBD patients and healthy individuals in Iran. Eur J Clin Microbiol Infect Dis 2017; 36:2335-2342. [PMID: 28741097 DOI: 10.1007/s10096-017-3065-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 07/04/2017] [Indexed: 12/19/2022]
Abstract
Blastocystis is a single-celled intestinal parasite commonly found in humans and a broad range of animals all over the world. In humans, its role in health and disease remains unsettled. The aim of our study was to investigate the distribution of Blastocystis and Blastocystis subtypes (ST) in patients with inflammatory bowel disease (IBD) and control subjects. A total of 71 stool samples were collected from IBD patients, 69 and 2 of whom had ulcerative colitis (UC) and Crohn's Disease (CD), respectively. Moreover, 166 stool samples from healthy subjects were included as control samples. All stool samples were cultivated, and 550-bp fragments of the small subunit ribosomal RNA gene was amplified from Blastocystis-positive cultures. All PCR-positive samples were sequenced. Blastocystis was observed in 9 (12.67%) and 35 (21.1%) IBD patients and healthy controls, respectively. There was no statistically significant correlation between IBD and presence of Blastocystis (P = 0.147). There was a statistically significant correlation between age and Blastocystis colonization in the IBD group (P < 0.05), but not among healthy controls. No significant correlation between gender and colonization was observed. ST1 and ST3 were obtained from 1 (12.5%) and 7 (87.5%) IBD patients, respectively, while in the healthy control group, subtypes 1, 2, and 3 were found in 14 (40%), 12 (34.28%), and 9 (25.72%), respectively. Phylogenetic analysis showed no variation in the distribution of subtypes nor intra-subtype genetic diversity between samples acquired from IBD patients and healthy controls. This study showed a trend towards a lower prevalence of Blastocystis in IBD patients than in control subjects. ST3 sequences isolated from IBD patients and control individuals did not appear to differ genetically.
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Affiliation(s)
- H Mirjalali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M R Abbasi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - N Naderi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Z Hasani
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - E S Mirsamadi
- Department of Microbiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - C R Stensvold
- Department of Bacteria, Parasites & Fungi, Infectious Disease Preparedness, Statens Serum Institut, Copenhagen, Denmark
| | - H Balaii
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - H Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - M R Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Gampa A, Engen PA, Shobar R, Mutlu EA. Relationships between gastrointestinal microbiota and blood group antigens. Physiol Genomics 2017; 49:473-483. [PMID: 28710295 PMCID: PMC5625272 DOI: 10.1152/physiolgenomics.00043.2017] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 07/11/2017] [Indexed: 12/25/2022] Open
Abstract
FUT2 is a gene for a fucosyltransferase that encodes expression of ABO blood group antigens found on gastrointestinal mucosa and secretions. We hypothesized that the fecal microbiomes of healthy subjects, with blood group antigens A, B, and O, have differing compositions. We analyzed 33 fecal and blood specimens from healthy subjects for FUT2 genotype, and the fecal microbiome was determined by 454 pyrosequencing. Our data show that being a blood group secretor is associated with less diversity at higher orders of taxonomy; and the presence of blood group A antigens in the secretor subjects are associated with an expansion families of bacteria within the gut. Furthermore, our study confirms the previous findings that secretors and nonsecretors have differing bacterial taxa. This extends the previous findings by demonstrating that the impact of being a nonsecretor is higher than that of individual blood group antigens. Additionally, we demonstrate that both secretor status and blood group antigen expression especially affect the Lachnospiraceae family of bacteria within the gut microbiome, with lower abundances noted in nonsecretors and higher abundances in secretors of various blood groups. We further note specific differences in blood group A-secretors demonstrating that the genus Blautia is lower in the group A-secretors compared with the non-A-secretors and that this reduction is accompanied by higher abundances of members of the Rikenellaceae, Peptostreptococcaceae, Clostridiales, and Turicibacter This study offers a first insight into the relationship between the fecal microbiome and blood group antigens in secretors.
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Affiliation(s)
- Anuhya Gampa
- Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois; and
| | - Phillip A Engen
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, Rush University Medical Center, Chicago, Illinois
| | - Rima Shobar
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, Rush University Medical Center, Chicago, Illinois
| | - Ece A Mutlu
- Department of Internal Medicine, Section of Gastroenterology, Hepatology and Nutrition, Rush University Medical Center, Chicago, Illinois
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Abstract
PURPOSE OF REVIEW According to the WHO reports, around 350 million people worldwide suffer from depression. Despite its high prevalence, the complex interaction of multiple mechanisms underlying depression still needs to be elucidated. RECENT FINDINGS Over the course of the last few years, several neurobiological alterations have been linked to the development and maintenance of depression. One basic process that seems to link many of these findings is inflammation. Chronic inflammation has been associated with both biological factors such as excessive neurotransmitter concentrations as well as psychological processes such as adult stress reactivity and a history of childhood trauma. As a balanced microbial community, modulated by diet, is a key regulator of the host physiology, it seems likely that gut microbiota plays a role in depression. SUMMARY The review summarizes the existent literature on this emerging research field and provides a comprehensive overview of the multifaceted links between the microbiota, diet, and depression. Several pathways linking early life trauma, pharmacological treatment effects, and nutrition to the microbiome in depression are described aiming to foster the psychotherapeutic treatment of depressed patients by interventions targeting the microbiota.
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Caenepeel C, Van Assche G. Whipping Crohn's With Helminth Therapies? Not Yet. J Crohns Colitis 2017; 11:387-389. [PMID: 28204053 DOI: 10.1093/ecco-jcc/jjx007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Accepted: 02/14/2017] [Indexed: 02/08/2023]
Affiliation(s)
- Clara Caenepeel
- Division of Gastroenterology and Hepatology and TARGID, KULeuven, Leuven, Belgium
| | - Gert Van Assche
- Division of Gastroenterology and Hepatology and TARGID, KULeuven, Leuven, Belgium
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13
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Schölmerich J, Fellermann K, Seibold FW, Rogler G, Langhorst J, Howaldt S, Novacek G, Petersen AM, Bachmann O, Matthes H, Hesselbarth N, Teich N, Wehkamp J, Klaus J, Ott C, Dilger K, Greinwald R, Mueller R, on behalf of the International TRUST-2 Study Group. A Randomised, Double-blind, Placebo-controlled Trial of Trichuris suis ova in Active Crohn's Disease. J Crohns Colitis 2017; 11:390-399. [PMID: 27707789 PMCID: PMC5881737 DOI: 10.1093/ecco-jcc/jjw184] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2016] [Accepted: 10/05/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS To investigate the efficacy and safety of three different dosages of embryonated, viable eggs of Trichuris suis [TSO] versus placebo for induction of remission in mildly-to-moderately active ileocolonic, uncomplicated Crohn's disease [CD]. METHODS Adults with active CD [n = 252] randomly received six fortnightly doses of 250, 2500, or 7500 TSO/15 ml suspension/day [TSO 250, TSO 2500, TSO 7500], or 15 ml placebo solution/day, in a double-blind fashion, with 4 weeks' follow-up. Primary endpoint was the rate of clinical remission [Crohn's Disease Activity Index [CDAI] < 150] at end of treatment, ie at Week 12 or withdrawal. Secondary endpoints included the course of clinical remission, rate of clinical response, change in CDAI, change in markers of inflammation, mucosal healing, and Physician's Global Assessment. RESULTS Clinical remission at Week 12 occurred in 38.5%, 35.2%, and 47.2% of TSO 250, TSO 2500, and TSO 7500 patients, respectively, and in 42.9% of placebo recipients. TSO induced a dose-dependent immunological response. There was no response regarding laboratory markers of inflammation. Other secondary efficacy variables also showed no advantage of TSO over placebo for treatment of active CD. Administration of TSO did not result in any serious adverse drug reaction. Review of non-serious suspected adverse drug reactions following TSO did not reveal any safety concerns. CONCLUSIONS Administration of 250-7500 TSO fortnightly over 12 weeks was safe and showed a dose-dependent immunological response, but no TSO dose showed a clinically relevant effect over placebo for induction of clinical remission or response in mildly-to-moderately active, ileocolonic CD.
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Affiliation(s)
- Jürgen Schölmerich
- Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany
| | | | - Frank W. Seibold
- Spital Netz Bern Tiefenau, Abt. Gastroenterologie, Bern, Switzerland
| | - Gerhard Rogler
- University of Zurich, Division of Gastroenterology and Hepatology, Zurich, Switzerland
| | - Jost Langhorst
- Kliniken Essen-Mitte, University of Duisburg-Essen, Integrative Gastroenterologie, Essen, Germany
| | - Stefanie Howaldt
- Hamburgisches Forschungsinstitut für CED, HaFCED GmbH&Co.KG, Hamburg, Germany
| | - Gottfried Novacek
- Medizinische Universität Wien, Universitätsklinik für Innere Medizin III, Vienna, Austria
| | - Andreas Munk Petersen
- Hvidovre University Hospital, Department of Gastroenterology and Department of Clinical Microbiology, Hvidovre, Denmark
| | | | - Harald Matthes
- Gemeinschaftskrankenhaus Havelhöhe, Abt. Gastroenterologie, Berlin, Germany
| | | | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten Leipzig & Schkeuditz, Leipzig, Germany
| | - Jan Wehkamp
- Robert-Bosch-Krankenhaus, Abt. Innere Medizin I, Stuttgart, Germany
| | - Jochen Klaus
- Universitätsklinikum Ulm, Klinik für Innere Medizin I, Ulm, Germany
| | - Claudia Ott
- University Hospital of Regensburg, Dept. of Internal Medicine I, Regensburg, Germany
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Saliganti V, Kapila R, Kapila S, Bhat MI. Probiotics in the modulation of maternal–infant immunity: Implications for allergic diseases. FOOD REVIEWS INTERNATIONAL 2016. [DOI: 10.1080/87559129.2016.1198913] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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15
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Sun CY, Bai J, Hu TY, Cheng BH, Ma L, Fan XQ, Yang PC, Zheng PY, Liu ZQ. CD4+ T cell responses in Balb/c mice with food allergy induced by trinitrobenzene sulfonic acid and ovalbumin. Mol Med Rep 2016; 13:5349-57. [PMID: 27109448 DOI: 10.3892/mmr.2016.5153] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 03/08/2016] [Indexed: 11/05/2022] Open
Abstract
The rapid increase in atopic diseases is potentially linked to increased hapten exposure, however, the role of haptens in the pathogenesis of food allergy remains unknown. Further studies are required to elucidate the cluster of differentiation 4 positive (CD4+) T cell response to food allergy induced by haptens. Dendritic cells were primed by trinitrobenzene sulfonic acid (TNBS) as a hapten or ovalbumin (OVA) as a model antigen, in a cell culture model. BALB/c mice were sensitized using TNBS and/or OVA. Intestinal Th1/Th2 cell and ovalbumin specific CD4+ T cells proliferation, intestinal cytokines (interleukin‑4 and interferon‑γ) in CD4+ T cells were evaluated. TNBS increased the expression of T cell immunoglobulin and mucin domain‑4 and tumor necrosis factor ligand superfamily member 4 in dendritic cells. Skewed Th2 cell polarization, extensive expression of interleukin‑4, reduced expression of interferon‑γ and forkhead box protein P3 were elicited following concomitant exposure to TNBS and OVA, with reduced regulatory T cells in the mouse intestinal mucosa, whereas a Th1 response was detected when challenged by TNBS or OVA alone. This data suggests that TNBS, as a hapten, combined with food antigens may lead to a Th2 cell response in the intestinal mucosa.
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Affiliation(s)
- Chen-Yi Sun
- Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Jie Bai
- Maternal and Child Care Service Centre of Zhengzhou, Zhengzhou, Henan 471000, P.R. China
| | - Tian-Yong Hu
- Shenzhen Key Laboratory of Ear, Nose and Throat (ENT), Department of Rhinology, Institute of ENT, Longgang ENT Hospital, Shenzhen, Guangdong 518116, P.R. China
| | - Bao-Hui Cheng
- Shenzhen Key Laboratory of Ear, Nose and Throat (ENT), Department of Rhinology, Institute of ENT, Longgang ENT Hospital, Shenzhen, Guangdong 518116, P.R. China
| | - Li Ma
- Shenzhen Key Laboratory of Ear, Nose and Throat (ENT), Department of Rhinology, Institute of ENT, Longgang ENT Hospital, Shenzhen, Guangdong 518116, P.R. China
| | - Xiao-Qin Fan
- Shenzhen Key Laboratory of Ear, Nose and Throat (ENT), Department of Rhinology, Institute of ENT, Longgang ENT Hospital, Shenzhen, Guangdong 518116, P.R. China
| | - Ping-Chang Yang
- Shenzhen Key Laboratory of Ear, Nose and Throat (ENT), Department of Rhinology, Institute of ENT, Longgang ENT Hospital, Shenzhen, Guangdong 518116, P.R. China
| | - Peng-Yuan Zheng
- Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Zhi-Qiang Liu
- Shenzhen Key Laboratory of Ear, Nose and Throat (ENT), Department of Rhinology, Institute of ENT, Longgang ENT Hospital, Shenzhen, Guangdong 518116, P.R. China
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Gonipeta B, Kim E, Gangur V. Mouse models of food allergy: how well do they simulate the human disorder? Crit Rev Food Sci Nutr 2016; 55:437-52. [PMID: 24915373 DOI: 10.1080/10408398.2012.657807] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Food allergy is a growing health problem with serious concerns due to high potential for fatality. Rapid advances in the knowledge on causes and mechanisms as well as in developing effective prevention/therapeutic strategies are needed. To meet these goals, mouse models that simulate the human disorder are highly desirable. During the past decade, several mouse models of food allergies have been reported. Here, we briefly reviewed the human disorder and then critically evaluated these models seeking answers to the following important questions: To what extent do they simulate the human disorder? What are the strengths and limitations of these models? What are the challenges facing this scientific area? Our analysis suggest that: (i) the mouse models, with inherent strengths and limitations, are available for many major food allergies; there is scope for additional model development and validation; (ii) models mostly simulate the severe forms of human disorder with similar immune and clinical features; (iii) the approaches used to develop some of the mouse models may be questionable; and (iv) the specific mechanisms of sensitization as wells as oral elicitation of fatal reactions in both humans and mice remains incompletely understood and therefore warrants further research.
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Affiliation(s)
- Babu Gonipeta
- a Food Allergy and Immunology Laboratory, Department of Food Science and Human Nutrition , Michigan State University , East Lansing , Michigan , USA
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17
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The Urban-Rural Gradient In Asthma: A Population-Based Study in Northern Europe. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2015; 13:ijerph13010093. [PMID: 26729146 PMCID: PMC4730484 DOI: 10.3390/ijerph13010093] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 12/10/2015] [Accepted: 12/15/2015] [Indexed: 12/14/2022]
Abstract
The early life environment appears to have a persistent impact on asthma risk. We hypothesize that environmental factors related to rural life mediate lower asthma prevalence in rural populations, and aimed to investigate an urban-rural gradient, assessed by place of upbringing, for asthma. The population-based Respiratory Health In Northern Europe (RHINE) study includes subjects from Denmark, Norway, Sweden, Iceland and Estonia born 1945–1973. The present analysis encompasses questionnaire data on 11,123 RHINE subjects. Six categories of place of upbringing were defined: farm with livestock, farm without livestock, village in rural area, small town, city suburb and inner city. The association of place of upbringing with asthma onset was analysed with Cox regression adjusted for relevant confounders. Subjects growing up on livestock farms had less asthma (8%) than subjects growing up in inner cities (11%) (hazard ratio 0.72 95% CI 0.57–0.91), and a significant urban-rural gradient was observed across six urbanisation levels (p = 0.02). An urban-rural gradient was only evident among women, smokers and for late-onset asthma. Analyses on wheeze and place of upbringing revealed similar results. In conclusion, this study suggests a protective effect of livestock farm upbringing on asthma development and an urban-rural gradient in a Northern European population.
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Sutharsan R, Mannan M, Doi SA, Mamun AA. Caesarean delivery and the risk of offspring overweight and obesity over the life course: a systematic review and bias-adjusted meta-analysis. Clin Obes 2015; 5:293-301. [PMID: 26286021 DOI: 10.1111/cob.12114] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Revised: 07/07/2015] [Accepted: 07/16/2015] [Indexed: 12/15/2022]
Abstract
A causal role of Caesarean delivery (CD) on developing overweight and obesity in the life course of offspring has been postulated. However, the true strength of this association is not clear and the potential for confounding has not been adequately addressed. A systematic review and meta-analysis were conducted to evaluate the strength of this association, this time using a bias-adjusted model in addition to conventional methods. Our search yielded 32 estimates from 14 publications (n = 261,000) for meta-analysis. The pooled analysis of seven estimates (n = 194,463) demonstrated a trend only towards a risk increase (RR = 1.15; 95% CI:0.94, 1.40) in overweight and obesity combined (ow+ob) due to CD in early childhood (0-5 years) and a similar trend was observed for mid-childhood and adolescence (5-18 years). In adulthood, a moderate increase in risk for ow+ob due to CD was observed (n = 30,200) (RR = 1.28; 95% CI 1.02, 1.34). Results for obesity and overweight separately were stronger for obesity and demonstrated a decreasing effect across the three life stages. Conventional methods of analysis suggested less uncertainty than we report and publication bias assessment was strongly suggestive of a bias in favour of positive studies. The current analysis therefore suggests that the small effects seen with CD in this and previous meta-analyses are probably a cumulative consequence of several biases we have outlined, including confounding effect and publication bias.
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Affiliation(s)
- R Sutharsan
- School of Public Health, The University of Queensland, Brisbane, QLD, Australia
- Eskitis Institute, Griffith University, Brisbane, QLD, Australia
| | - M Mannan
- School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia
| | - S A Doi
- Research School of Population Health, Australian National University, Canberra, ACT, Australia
| | - A A Mamun
- School of Public Health, The University of Queensland, Brisbane, QLD, Australia
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19
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Murch SH. Adverse Reactions to Foods. Clin Nutr 2015. [DOI: 10.1002/9781119211945.ch8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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20
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Leonardi I, Nicholls F, Atrott K, Cee A, Tewes B, Greinwald R, Rogler G, Frey-Wagner I. Oral administration of dextran sodium sulphate induces a caecum-localized colitis in rabbits. Int J Exp Pathol 2015; 96:151-62. [PMID: 25716348 DOI: 10.1111/iep.12117] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2014] [Accepted: 12/09/2014] [Indexed: 12/23/2022] Open
Abstract
Trichuris suis ova (TSO) have shown promising results in the treatment of inflammatory bowel disease (IBD) but the mechanisms which underlies this therapeutic effect cannot be studied in mice and rats as T. suis fails to colonize the rodent intestine, whilst hatching in humans and rabbits. As a suitable rabbit IBD model is currently not available, we developed a rabbit colitis model by administration of dextran sodium sulphate (DSS). White Himalayan rabbits (n = 12) received 0.1% DSS in the daily water supply for five days. Clinical symptoms were monitored daily, and rabbits were sacrificed at different time points. A genomewide expression analysis was performed with RNA isolated from caecal lamina propria mononuclear cells (LPMC) and intestinal epithelial cells (IEC). The disease activity index of DSS rabbits increased up to 2.1 ± 0.4 (n = 6) at day 10 (controls <0.5). DSS induced a caecum-localized pathology with crypt architectural distortion, stunted villous surface and inflammatory infiltrate in the lamina propria. The histopathology score reached a peak of 14.2 ± 4.9 (n = 4) at day 10 (controls 7.7 ± 0.9, n = 5). Expression profiling revealed an enrichment of IBD-related genes in both LPMC and IEC. Innate inflammatory response, Th17 signalling and chemotaxis were among the pathways affected significantly. We describe a reproducible and reliable rabbit model of DSS colitis. Localization of the inflammation in the caecum and its similarities to IBD make this model particularly suitable to study TSO therapy in vivo.
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Affiliation(s)
- Irina Leonardi
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Flora Nicholls
- Central Biological Laboratory, University Hospital Zurich, Zurich, Switzerland
| | - Kirstin Atrott
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Alexandra Cee
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Bernhard Tewes
- Research and Development, Dr. Falk Pharma GmbH, Freiburg, Germany
| | - Roland Greinwald
- Research and Development, Dr. Falk Pharma GmbH, Freiburg, Germany
| | - Gerhard Rogler
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Isabelle Frey-Wagner
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
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21
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Rossen NG, Bart A, Verhaar N, van Nood E, Kootte R, de Groot PF, D'Haens GR, Ponsioen CY, van Gool T. Low prevalence of Blastocystis sp. in active ulcerative colitis patients. Eur J Clin Microbiol Infect Dis 2015; 34:1039-44. [PMID: 25680316 PMCID: PMC4409634 DOI: 10.1007/s10096-015-2312-2] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Accepted: 01/06/2015] [Indexed: 12/17/2022]
Abstract
Ulcerative colitis (UC) is thought to originate from a disbalance in the interplay between the gut microbiota and the innate and adaptive immune system. Apart from the bacterial microbiota, there might be other organisms, such as parasites or viruses, that could play a role in the aetiology of UC. The primary objective of this study was to compare the prevalence of Blastocystis sp. in a cohort of patients with active UC and compare that to the prevalence in healthy controls. We studied patients with active UC confirmed by endoscopy included in a randomised prospective trial on the faecal transplantation for UC. A cohort of healthy subjects who served as donors in randomised trials on faecal transplantation were controls. Healthy subjects did not have gastrointestinal symptoms and were extensively screened for infectious diseases by a screenings questionnaire, extensive serologic assessment for viruses and stool analysis. Potential parasitic infections such as Blastocystis were diagnosed with the triple faeces test (TFT). The prevalence of Blastocystis sp. were compared between groups by Chi-square testing. A total of 168 subjects were included, of whom 45 had active UC [median age 39.0 years, interquartile range (IQR) 32.5–49.0, 49 % male] and 123 were healthy subjects (median age 27 years, IQR 22.0–37.0, 54 % male). Blastocystis sp. was present in the faeces of 40/123 (32.5 %) healthy subjects and 6/45 (13.3 %) UC patients (p = 0.014). Infection with Blastocystis is significantly less frequent in UC patients as compared to healthy controls.
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Affiliation(s)
- N G Rossen
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
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22
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van de Velde J, Wilbers RHP, Westerhof LB, van Raaij DR, Stavrakaki I, Sonnenberg ASM, Bakker J, Schots A. Assessing the immunomodulatory potential of high-molecular-weight extracts from mushrooms; an assay based on THP-1 macrophages. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2015; 95:344-350. [PMID: 24799300 DOI: 10.1002/jsfa.6726] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 04/28/2014] [Accepted: 04/28/2014] [Indexed: 06/03/2023]
Abstract
BACKGROUND Food is a potential source of immunomodulating compounds that may be used to steer immune responses towards a desired status such as reducing inflammatory disorders. However, to identify and characterize such bioactive compounds, biologically relevant and standardized assays are required. Macrophages play an important role in immunomodulation and are suited for developing cell-based assays. An assay was developed based on macrophages, in a homogeneous differentiation state, using the human monocytic cell line THP-1 previously used to assess immunomodulatory properties of low-molecular-weight allergens, hormones, dietary supplements and therapeutic drugs. RESULTS Zymosan and mushroom polysaccharide extracts lead to a heterogeneous differentiation state of THP-1 monocytes, and these cells secrete low levels of cytokines upon stimulation. Differentiation into macrophages using a low concentration of phorbol 12-myristate 13-acetate improved responsiveness. Elevated levels of cytokines were secreted by cells in a homogenous differentiation state. In addition, it was determined that the assay performs best when using cells at a concentration of (2.5-5) × 10(5) cells mL(-1). CONCLUSION An assay was developed suitable to distinguish the immunomodulatory properties of food compounds in a reproducible manner. It was evaluated using eight mushroom species by measuring the secretion of relevant cytokines TNF-α, IL-1β, IL-6 and IL-10.
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Affiliation(s)
- Jan van de Velde
- Plant Sciences Group, Wageningen University and Research Centre, Wageningen, The Netherlands
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Abstract
During the last 20 years, treatment paradigms as well as drugs used for IBD have changed significantly. However, there are still many unmet needs and a significant number of patients needing better therapy. It is obvious from this situation that many attempts have been made to implement new drugs and treatment algorithms including biologicals, new formulations of old drugs and 'fancy molecules or approaches'. For about 10 years, the application of Trichuris suis ova has been promoted and used in quite a number of patients. Two early studies suggested positive effects in ulcerative colitis as well as in Crohn's disease. These studies were based on experimental data in animal models as well as in vitro experiments. However, two large randomized controlled trials were not able to provide significant clinical effects in active Crohn's disease as compared to placebo, although a biological reaction (eosinophilia) was found. Another approach is the use of locally released phosphatidylcholine in ulcerative colitis. This approach is based on decreased phosphatidylcholine concentrations in the colonic mucus in patients, and showed positive effects in a number of monocentric trials in steroid-refractory and chronic active ulcerative colitis. A dose-finding study gave a positive signal in the highest-dose group and this approach is being tested further in controlled trials. Many other 'fancy molecules' including cannabis, vitamin D, thalidomide, hyaluronic acid, lidocaine, clonidine, chondroitin sulfate, naltrexone and melatonin have been tested in patients with claims of success. For most of those, however, controlled data in appropriate studies are lacking. Many more substances have been used in animal models and are probably applied in individual patients. Results of preliminary studies on some of the molecules mentioned are presented.
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Affiliation(s)
- Jürgen Schölmerich
- University Hospital Frankfurt, Johann Wolfgang Goethe University Frankfurt am Main, Frankfurt am Main, Germany
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Peng J, Narasimhan S, Marchesi JR, Benson A, Wong FS, Wen L. Long term effect of gut microbiota transfer on diabetes development. J Autoimmun 2014; 53:85-94. [PMID: 24767831 PMCID: PMC4361177 DOI: 10.1016/j.jaut.2014.03.005] [Citation(s) in RCA: 115] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 03/23/2014] [Accepted: 03/30/2014] [Indexed: 12/12/2022]
Abstract
The composition of the gut microbiome represents a very important environmental factor that influences the development of type 1 diabetes (T1D). We have previously shown that MyD88-deficient non-obese diabetic (MyD88-/-NOD) mice, that were protected from T1D development, had a different composition of gut microbiota compared to wild type NOD mice. The aim of our study was to investigate whether this protection could be transferred. We demonstrate that transfer of gut microbiota from diabetes-protected MyD88-deficient NOD mice, reduced insulitis and significantly delayed the onset of diabetes. Gut bacteria from MyD88-deficient mice, administered over a 3-week period, starting at 4 weeks of age, stably altered the family composition of the gut microbiome, with principally Lachnospiraceae and Clostridiaceae increased and Lactobacillaceae decreased. The transferred mice had a higher concentration of IgA and TGFβ in the lumen that was accompanied by an increase in CD8(+)CD103(+) and CD8αβ T cells in the lamina propria of the large intestine. These data indicate not only that gut bacterial composition can be altered after the neonatal/weaning period, but that the composition of the microbiome affects the mucosal immune system and can delay the development of autoimmune diabetes. This result has important implications for the development of probiotic treatment for T1D.
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Affiliation(s)
- Jian Peng
- Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Sukanya Narasimhan
- Section of Infectious Disease, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Julian R Marchesi
- Cardiff School of Biosciences, Main Building, Museum Avenue, Cardiff University, Cardiff, UK; Centre for Digestive and Gut Health, Imperial College London, London, UK
| | - Andrew Benson
- Department of Food Science and Technology, University of Nebraska, Lincoln, NE, USA
| | - F Susan Wong
- Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, UK
| | - Li Wen
- Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
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Canova C, Zabeo V, Pitter G, Romor P, Baldovin T, Zanotti R, Simonato L. Association of maternal education, early infections, and antibiotic use with celiac disease: a population-based birth cohort study in northeastern Italy. Am J Epidemiol 2014; 180:76-85. [PMID: 24853109 DOI: 10.1093/aje/kwu101] [Citation(s) in RCA: 106] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
We conducted a population-based birth cohort study of approximately 203,000 babies born in northeastern Italy (1989-2012) to investigate perinatal variables, early infections leading to hospital admission, and antibiotic use in the first 12 months of life as possible risk factors for celiac disease (CD). Incident CD cases were identified from pathology reports, hospital discharge records, and exemptions from prescription charges for clinical tests. Multivariate Poisson regression models were fitted to estimate incidence rate ratios (IRRs). A total of 1,227 children had CD; CD was histopathologically confirmed in 866 (71%). Female sex, maternal age, and high maternal educational level were found to be significantly associated with CD. Gastrointestinal infections were strongly associated with a subsequent diagnosis of CD (IRR = 2.04, 95% confidence interval (CI): 1.30, 3.22). Antibiotic use was significantly associated with CD onset (IRR = 1.24, 95% CI: 1.07, 1.43), with a dose-response relationship for number of courses (P-trend < 0.01). Cephalosporin use strongly increased the risk of CD (IRR = 1.42, 95% CI: 1.18, 1.73). Use of antibiotics (supported by the dose-response relationship) and gastrointestinal infections in the first year of life may facilitate the early onset of CD by altering intestinal microflora and the gut mucosal barrier. Perinatal factors, including cesarean section, had little influence on the risk of childhood CD.
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Timm S, Svanes C, Janson C, Sigsgaard T, Johannessen A, Gislason T, Jogi R, Omenaas E, Forsberg B, Torén K, Holm M, Bråbäck L, Schlünssen V. Place of upbringing in early childhood as related to inflammatory bowel diseases in adulthood: a population-based cohort study in Northern Europe. Eur J Epidemiol 2014; 29:429-37. [PMID: 24916994 PMCID: PMC4065648 DOI: 10.1007/s10654-014-9922-3] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Accepted: 05/26/2014] [Indexed: 12/21/2022]
Abstract
Background The two inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, has increased rapidly during the twentieth century, but the aetiology is still poorly understood. Impaired immunological competence due to decreasing biodiversity and altered microbial stimulation is a suggested explanation. Objective Place of upbringing was used as a proxy for the level and diversity of microbial stimulation to investigate the effects on the prevalence of IBD in adulthood. Methods Respiratory Health in Northern Europe (RHINE) III is a postal follow-up questionnaire of the European Community Respiratory Health Survey (ECRHS) cohorts established in 1989–1992. The study population was 10,864 subjects born 1945–1971 in Denmark, Norway, Sweden, Iceland and Estonia, who responded to questionnaires in 2000–2002 and 2010–2012. Data were analysed in logistic and Cox regression models taking age, sex, smoking and body mass index into consideration. Results Being born and raised on a livestock farm the first 5 years of life was associated with a lower risk of IBD compared to city living in logistic (OR 0.54, 95 % CI 0.31; 0.94) and Cox regression models (HR 0.55, 95 % CI 0.31; 0.98). Random-effect meta-analysis did not identify geographical difference in this association. Furthermore, there was a significant trend comparing livestock farm living, village and city living (p < 0.01). Sub-analyses showed that the protective effect was only present among subjects born after 1952 (OR 0.25, 95 % CI 0.11; 0.61). Conclusion This study suggests a protective effect from livestock farm living in early childhood on the occurrence of IBD in adulthood, however only among subjects born after 1952. We speculate that lower microbial diversity is an explanation for the findings.
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Affiliation(s)
- Signe Timm
- Department of Public Health, Aarhus University, Bartholins Allé 2, Building 1260, 8000, Århus, Denmark,
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Bénardais K, Gudi V, Gai L, Neßler J, Singh V, Prajeeth CK, Skripuletz T, Stangel M. Long-term impact of neonatal inflammation on demyelination and remyelination in the central nervous system. Glia 2014; 62:1659-70. [PMID: 24909143 DOI: 10.1002/glia.22706] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2014] [Revised: 05/21/2014] [Accepted: 05/23/2014] [Indexed: 12/12/2022]
Abstract
Perinatal inflammation causes immediate changes of the blood-brain barrier (BBB) and thus may have different consequences in adult life including an impact on neurological diseases such as demyelinating disorders. In order to determine if such a perinatal insult affects the course of demyelination in adulthood as "second hit," we simulated perinatal bacterial inflammation by systemic administration of lipopolysaccharide (LPS) to either pregnant mice or newborn animals. Demyelination was later induced in adult animals by cuprizone [bis(cyclohexylidenehydrazide)], which causes oligodendrocyte death with subsequent demyelination accompanied by strong microgliosis and astrogliosis. A single LPS injection at embryonic day 13.5 did not have an impact on demyelination in adulthood. In contrast, serial postnatal LPS injections (P0-P8) caused an early delay of myelin removal in the corpus callosum, which was paralleled by reduced numbers of activated microglia. During remyelination, postnatal LPS treatment enhanced early remyelination with a concomitant increase of mature oligodendrocytes. Furthermore, the postnatal LPS challenge impacts the phenotype of microglia since an elevated mRNA expression of microglia related genes such as TREM 2, CD11b, TNF-α, TGF-β1, HGF, FGF-2, and IGF-1 was found in these preconditioned mice during early demyelination. These data demonstrate that postnatal inflammation has long-lasting effects on microglia functions and modifies the course of demyelination and remyelination in adulthood.
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Affiliation(s)
- Karelle Bénardais
- Department of Neurology, Hannover Medical School, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany
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Pascual V, Dieli-Crimi R, López-Palacios N, Bodas A, Medrano LM, Núñez C. Inflammatory bowel disease and celiac disease: Overlaps and differences. World J Gastroenterol 2014; 20:4846-4856. [PMID: 24803796 PMCID: PMC4009516 DOI: 10.3748/wjg.v20.i17.4846] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Accepted: 01/15/2014] [Indexed: 02/06/2023] Open
Abstract
Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults.
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Gilissen LJ, van der Meer IM, Smulders MJ. Reducing the incidence of allergy and intolerance to cereals. J Cereal Sci 2014. [DOI: 10.1016/j.jcs.2014.01.005] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Cooper PJ, Vaca M, Rodriguez A, Chico ME, Santos DN, Rodrigues LC, Barreto ML. Hygiene, atopy and wheeze-eczema-rhinitis symptoms in schoolchildren from urban and rural Ecuador. Thorax 2014; 69:232-9. [PMID: 24105783 PMCID: PMC3932750 DOI: 10.1136/thoraxjnl-2013-203818] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Revised: 08/20/2013] [Accepted: 09/16/2013] [Indexed: 11/24/2022]
Abstract
BACKGROUND Rural residence is protective against atopy and wheeze-rhinitis-eczema symptoms in developed countries, an effect attributed to farming and poor hygiene exposures. There are few data from developing countries addressing this question. We compared atopy and wheeze-rhinitis-eczema symptoms between urban and rural Ecuador, and explored the effects of farming and poor hygiene exposures. METHODS We performed cross sectional studies of schoolchildren living in rural and urban Ecuador. Data on symptoms and farming/hygiene exposures were collected by parental questionnaire, atopy by allergen skin prick test reactivity and geohelminth infections by stool examinations. RESULTS Among 2526 urban and 4295 rural schoolchildren, prevalence was: atopy (10.0% vs 12.5%, p=0.06), wheeze (9.4% vs 10.1%, p=0.05), rhinitis (8.1% vs 6.4%, p=0.02) and eczema (5.9% vs 4.7%, p=0.06). A small proportion of symptoms were attributable to atopy (range 3.9-10.7%) with greater attributable fractions for respiratory symptoms observed in urban schoolchildren. Respiratory symptoms were associated with poor hygiene/farming exposures: wheeze with lack of access to potable water; and rhinitis with household pets, no bathroom facilities and contact with large farm animals. Birth order was inversely associated with respiratory symptoms. Area of residence and atopy had few effects on these associations. CONCLUSIONS Urban schoolchildren living in Ecuador have a similar prevalence of atopy, eczema and wheeze but a higher prevalence of rhinitis compared with rural children. Some farming and poor hygiene exposures were associated with an increase in the prevalence of wheeze or rhinitis while birth order was inversely associated with these symptoms.
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Affiliation(s)
- Philip J Cooper
- Laboratorio de Investigaciones FEPIS, Quinindé, Esmeraldas Province, Ecuador
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Abstract
Some but not all epidemiological studies suggest that helminth infection in childhood protects against development of inflammatory bowel disease (IBD) in later years. In animal models of IBD, helminths have shown protective effects and changed bacterial flora in the gut. Based on these concepts, small trials and series have been published showing some positive effects of Trichuris suis ova in ulcerative colitis and Crohn's disease. Currently, large randomized placebo-controlled trials are under way. Results remain to be awaited in order to clarify a possible role of T. suis ova in the treatment of IBD.
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Affiliation(s)
- Jürgen Schölmerich
- University Hospital, Johann Wolfgang Goethe-Universität Frankfurt/Main, Frankfurt/Main, Germany
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Perricone C, Colafrancesco S, Mazor RD, Soriano A, Agmon-Levin N, Shoenfeld Y. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects. J Autoimmun 2013; 47:1-16. [PMID: 24238833 DOI: 10.1016/j.jaut.2013.10.004] [Citation(s) in RCA: 164] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2013] [Accepted: 10/21/2013] [Indexed: 12/23/2022]
Abstract
In 2011 a new syndrome termed 'ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants' was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with post-vaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance.
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Affiliation(s)
- Carlo Perricone
- The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy
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Abstract
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that belongs to the family of basic helix-loop-helix transcription factors. Although the AhR was initially recognized as the receptor mediating the pathologic effects of dioxins and other pollutants, the activation of AhR by endogenous and environmental factors has important physiologic effects, including the regulation of the immune response. Thus, the AhR provides a molecular pathway through which environmental factors modulate the immune response in health and disease. In this review, we discuss the role of AhR in the regulation of the immune response, the source and chemical nature of AhR ligands, factors controlling production and degradation of AhR ligands, and the potential to target the AhR for therapeutic immunomodulation.
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Affiliation(s)
- Francisco J Quintana
- Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
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The management of paediatric allergy: not everybody's cup of tea--10-11th February 2012. Curr Opin Allergy Clin Immunol 2013; 13 Suppl 1:S1-50. [PMID: 23377496 DOI: 10.1097/aci.0b013e32835e8b94] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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35
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Petersen AM, Stensvold CR, Mirsepasi H, Engberg J, Friis-Møller A, Porsbo LJ, Hammerum AM, Nordgaard-Lassen I, Nielsen HV, Krogfelt KA. Active ulcerative colitis associated with low prevalence of Blastocystis and Dientamoeba fragilis infection. Scand J Gastroenterol 2013; 48:638-9. [PMID: 23528075 DOI: 10.3109/00365521.2013.780094] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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Vitetta L, Gobe G. Uremia and chronic kidney disease: the role of the gut microflora and therapies with pro- and prebiotics. Mol Nutr Food Res 2013; 57:824-32. [PMID: 23450842 DOI: 10.1002/mnfr.201200714] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Revised: 12/10/2012] [Accepted: 12/18/2012] [Indexed: 12/17/2022]
Abstract
Uremia is an illness that accompanies kidney failure and chronic kidney disease (CKD). Uremic illness is considered to be due largely to the accumulation of organic waste products that are normally cleared by the kidneys. However, uremic retention solutes are generated in part in the gastrointestinal tract (GIT), with the gut microbiota and the ensuing micro-biometabolome playing a significant role in the proliferation of uremic retention solutes. Toxins generated in, or introduced into the body via the intestine, such as advanced glycation end products, phenols, and indoles, all may contribute to the pathogenesis of CKD. Hence, it is biologically plausible, but not well recognized, that an important participant in the toxic load that contributes to CKD originates in the GIT. The microbiota that colonize the GIT perform a number of functions that include regulating the normal development and function of the mucosal barriers; assisting with maturation of immunological tissues, which in turn promotes immunological tolerance to antigens from foods, the environment, or potentially pathogenic organisms; controlling nutrient uptake and metabolism; and preventing propagation of pathogenic micro-organisms. Here, we develop a hypothesis that probiotics and prebiotics have a therapeutic role in maintaining a metabolically balanced GIT, and reducing progression of CKD and associated uremia.
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Affiliation(s)
- Luis Vitetta
- Centre for Integrative Clinical and Molecular Medicine, School of Medicine at Princess Alexandra Hospital, The University of Queensland, Brisbane, Australia
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Svensson E, Hyde M, Modi N, Ehrenstein V. Caesarean section and body mass index among Danish men. Obesity (Silver Spring) 2013; 21:429-33. [PMID: 23408746 DOI: 10.1002/oby.20310] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2012] [Accepted: 12/04/2012] [Indexed: 12/15/2022]
Abstract
OBJECTIVE We conducted a prevalence study to examine the association between Caesarean section and body mass index (BMI) in 21,051 adult Danish men born in 1977-1983 who presented for mandatory conscription evaluation around age 18 years. DESIGN AND METHODS Data on BMI from conscription records were linked to the men's birth records to identify mode of delivery and other perinatal data. RESULTS Two thousand one hundred thirty-eight men (10%) had been delivered by a Caesarean section. Prevalence of obesity at conscription was 6% for those born vaginally and 9% for those born by a Caesarean section. The adjusted prevalence ratio (PR) for obesity (BMI ≥ 30 kg/m(2) ) was 1.35 (95% CI 1.14-1.60); the adjusted PR for overweight (25 ≤ BMI < 30 kg/m(2) ) was 1.05 (95% CI 0.94-1.17). The adjusted mean difference in BMI was 0.38 kg/m(2) (95% CI 0.16-0.60) comparing men born by Caesarean versus vaginal delivery. The estimates were similar for planned and nonplanned Caesarean deliveries. CONCLUSION Birth by a Caesarean section was associated with an increased risk of obesity among men.
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Affiliation(s)
- Elisabeth Svensson
- Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
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Lighter-Fisher J, Peng CH. Infection with Mycobacterium tuberculosis Is Inversely Associated with Childhood Asthma. PEDIATRIC ALLERGY IMMUNOLOGY AND PULMONOLOGY 2012. [DOI: 10.1089/ped.2012.0146] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Jennifer Lighter-Fisher
- Saul Krugman Division of Pediatric Infectious Diseases and Immunology, New York University School of Medicine, New York, New York
| | - Chia-Hui Peng
- Saul Krugman Division of Pediatric Infectious Diseases and Immunology, New York University School of Medicine, New York, New York
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Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra. Curr Gerontol Geriatr Res 2012; 2012:302875. [PMID: 22536229 PMCID: PMC3318212 DOI: 10.1155/2012/302875] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2011] [Accepted: 12/19/2011] [Indexed: 01/22/2023] Open
Abstract
Compartmentalized redox faults are common to ageing diseases. Dietary constituents are catabolized to NAD(H) donating electrons producing proton-based bioenergy in coevolved, cross-species and cross-organ networks. Nicotinamide and NAD deficiency from poor diet or high expenditure causes pellagra, an ageing and dementing disorder with lost robustness to infection and stress. Nicotinamide and stress induce Nicotinamide-N-methyltransferase (NNMT) improving choline retention but consume methyl groups. High NNMT activity is linked to Parkinson's, cancers, and diseases of affluence. Optimising nicotinamide and choline/methyl group availability is important for brain development and increased during our evolution raising metabolic and methylome ceilings through dietary/metabolic symbiotic means but strict energy constraints remain and life-history tradeoffs are the rule. An optimal energy, NAD and methyl group supply, avoiding hypo and hyper-vitaminoses nicotinamide and choline, is important to healthy ageing and avoids utilising double-edged symbionts or uncontrolled autophagy or reversions to fermentation reactions in inflammatory and cancerous tissue that all redistribute NAD(P)(H), but incur high allostatic costs.
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Abstract
There have been numerous methods and ways to classify autoimmune diseases. By far, the most traditional has been to separate immune-mediated pathology into organ-specific and organ-non-specific diseases. The classic systemic autoimmune diseases are, of course, rheumatoid arthritis and systemic lupus. The classic organ-specific autoimmune diseases have been autoimmune thyroiditis and autoimmune gastritis. However, as our understanding of the loss of tolerance has expanded, so has the long list of autoimmune diseases. In many cases, the distinction between organ-specific and organ-non-specific or systemic autoimmunity becomes a blur. In this issue, we discuss recent concepts in autoimmune pancreatitis, primary sclerosing cholangitis, Goodpasture's syndrome, myofasciitis, type I diabetes, polymyositis, autoimmune thyroid disease, IgA nephropathy, autoimmune uveitis, and ANCA-associated vasculitis. Common themes on both etiology and effector mechanisms are described throughout these papers with an attempt to provide a cutting-edge overview.
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Björkstén B. Diverse microbial exposure - consequences for vaccine development. Vaccine 2011; 30:4336-40. [PMID: 22079075 DOI: 10.1016/j.vaccine.2011.10.074] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2011] [Revised: 10/17/2011] [Accepted: 10/26/2011] [Indexed: 01/08/2023]
Abstract
Numerous epidemiological studies suggest that there is an inverse relationship between "immunologically mediated diseases of affluence", such as allergy, diabetes and inflammatory bowel disease on one hand and few infections encountered in early childhood, on the other hand. Careful analysis of the epidemiological, clinical and animal studies taken together, however, suggests that the protection is mediated by broad exposure to a wealth of commensal, non-pathogenic microorganisms early in life, rather than by infections. Microbial exposure has little relationship with "hygiene" in the usual meaning of the word and the term "hygiene hypothesis" is therefore misleading. A better term would be "microbial deprivation hypothesis". The suggestion that childhood infections would protect against allergic disease led to unfortunate speculations that vaccinations would increase the risk for allergies and diabetes. Numerous epidemiological studies have therefore been conducted, searching for a possible relationship between various childhood vaccinations on one hand and allergy on the other hand. It is reasonable from these studies to conclude that vaccinations against infectious agents neither significantly increase, nor reduce the likelihood of immunologically mediated diseases. It is established that the postnatal maturation of immune regulation is largely driven by exposure to microbes. Germ free animals manifest excessive immune responses when immunised and they do not develop normal immune regulatory function. The gut is by far the largest source of microbial exposure, as the human gut microbiome contains up to 1014 bacteria, i.e. ten times the number of cells in the human body. Several studies in recent years have shown differences in the composition of the gut microbiota between allergic and non-allergic individuals and between infants living in countries with a low and a high prevalence of immune mediated diseases. The administration of probiotic bacteria to pregnant mothers and postnatal to their infants has immune modulatory effects. So far, however, probiotic bacteria do not seem to significantly enhance immune responses to vaccines. The potential to improve vaccine responses by modifying the gut microbiota in infants and the possibility to employ probiotic bacteria as adjuvants and/or delivery vehicles, is currently explored in several laboratories. Although to date few clinical results have been reported, experimental studies have shown some encouraging results.
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Affiliation(s)
- Bengt Björkstén
- Institute of Environmental Medicine, Karolinska Institutet Stockholm, and School of Health and Medical Sciences, Örebro University, Sweden.
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Stockinger S, Hornef MW, Chassin C. Establishment of intestinal homeostasis during the neonatal period. Cell Mol Life Sci 2011; 68:3699-712. [PMID: 21952827 PMCID: PMC11114965 DOI: 10.1007/s00018-011-0831-2] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2011] [Revised: 09/07/2011] [Accepted: 09/07/2011] [Indexed: 12/15/2022]
Abstract
The intestinal mucosa faces the challenge of regulating the balance between immune tolerance towards commensal bacteria, environmental stimuli and food antigens on the one hand, and induction of efficient immune responses against invading pathogens on the other hand. This regulatory task is of critical importance to prevent inappropriate immune activation that may otherwise lead to chronic inflammation, tissue disruption and organ dysfunction. The most striking example for the efficacy of the adaptive nature of the intestinal mucosa is birth. Whereas the body surfaces are protected from environmental and microbial exposure during fetal life, bacterial colonization and contact with potent immunostimulatory substances start immediately after birth. In the present review, we summarize the current knowledge on the mechanisms underlying the transition of the intestinal mucosa during the neonatal period leading to the establishment of a stable, life-long host-microbial homeostasis. The environmental exposure and microbial colonization during the neonatal period, and also the influence of maternal milk on the immune protection of the mucosa and the role of antimicrobial peptides, are described. We further highlight the molecular mechanisms of innate immune tolerance in neonatal intestinal epithelium. Finally, we link the described immunoregulatory mechanisms to the increased susceptibility to inflammatory and infectious diseases during the neonatal period.
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Affiliation(s)
- Silvia Stockinger
- Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany
| | - Mathias W. Hornef
- Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany
| | - Cécilia Chassin
- Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany
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