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      Association between maternal vegetable intake during pregnancy and allergy in offspring: Japan Environment and Children’s Study

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          Abstract

          The association between maternal diet during pregnancy and allergy in offspring remains contentious. Here, we examined the association between maternal intake of vegetables and related nutrients during pregnancy and allergic diseases in offspring at one year of age. A cohort of 80,270 pregnant women enrolled in the Japan Environment and Children’s Study were asked to respond to a food frequency questionnaire during pregnancy and the International Study of Asthma and Allergies in Childhood questionnaire at one year postpartum. The women were categorized into quintiles according to the energy-adjusted maternal intake of vegetables and related nutrients. Using the categorizations as exposure variables, the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were determined for the allergic outcomes, including asthma, wheeze, atopic dermatitis, eczema, and food allergy, in the offspring per quintile at one year of age. Of the 80,270 participants, 2,027 (2.5%), 15,617 (19.6%), 3,477 (4.3%), 14,929 (18.7%), 13,801 (17.2%), and 25,028 (31.3%) children experienced asthma, wheeze, atopic dermatitis, eczema, food allergy, and some form of allergic disease, respectively. The aORs of each quintile of maternal vegetable intake for all allergic outcomes were close to 1.0 compared to the lowest quintile. The lowest aOR was found in the association of maternal cruciferous vegetable intake with asthma (aOR: 0.82, 95% CI: 0.70–0.96) and highest was found in the association of maternal total vegetable intake with atopic dermatitis (aOR: 1.17, 95% CI: 1.04–1.31). The risk of allergic outcomes for the various nutrients related to vegetable consumption was close to 1.0. The maternal intake of vegetables and various related nutrients during pregnancy had little or no association with any of the allergic outcomes, including asthma, wheezing, atopic dermatitis, eczema, and food allergy, in offspring at one year.

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          Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis.

          Metabolites from intestinal microbiota are key determinants of host-microbe mutualism and, consequently, the health or disease of the intestinal tract. However, whether such host-microbe crosstalk influences inflammation in peripheral tissues, such as the lung, is poorly understood. We found that dietary fermentable fiber content changed the composition of the gut and lung microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The gut microbiota metabolized the fiber, consequently increasing the concentration of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease. Treatment of mice with the SCFA propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 (TH2) cell effector function. The effects of propionate on allergic inflammation were dependent on G protein-coupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show that dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation.
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            Rationale and study design of the Japan environment and children’s study (JECS)

            Background There is global concern over significant threats from a wide variety of environmental hazards to which children face. Large-scale and long-term birth cohort studies are needed for better environmental management based on sound science. The primary objective of the Japan Environment and Children’s Study (JECS), a nation-wide birth cohort study that started its recruitment in January 2011, is to elucidate environmental factors that affect children’s health and development. Methods/Design Approximately 100,000 expecting mothers who live in designated study areas will be recruited over a 3-year period from January 2011. Participating children will be followed until they reach 13 years of age. Exposure to environmental factors will be assessed by chemical analyses of bio-specimens (blood, cord blood, urine, breast milk, and hair), household environment measurements, and computational simulations using monitoring data (e.g. ambient air quality monitoring) as well as questionnaires. JECS’ priority outcomes include reproduction/pregnancy complications, congenital anomalies, neuropsychiatric disorders, immune system disorders, and metabolic/endocrine system disorders. Genetic factors, socioeconomic status, and lifestyle factors will also be examined as covariates and potential confounders. To maximize representativeness, we adopted provider-mediated community-based recruitment. Discussion Through JECS, chemical substances to which children are exposed during the fetal stage or early childhood will be identified. The JECS results will be translated to better risk assessment and management to provide healthy environment for next generations.
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              Baseline Profile of Participants in the Japan Environment and Children’s Study (JECS)

              Background The Japan Environment and Children’s Study (JECS), known as Ecochil-Chosa in Japan, is a nationwide birth cohort study investigating the environmental factors that might affect children’s health and development. We report the baseline profiles of the participating mothers, fathers, and their children. Methods Fifteen Regional Centres located throughout Japan were responsible for recruiting women in early pregnancy living in their respective recruitment areas. Self-administered questionnaires and medical records were used to obtain such information as demographic factors, lifestyle, socioeconomic status, environmental exposure, medical history, and delivery information. In the period up to delivery, we collected bio-specimens, including blood, urine, hair, and umbilical cord blood. Fathers were also recruited, when accessible, and asked to fill in a questionnaire and to provide blood samples. Results The total number of pregnancies resulting in delivery was 100,778, of which 51,402 (51.0%) involved program participation by male partners. Discounting pregnancies by the same woman, the study included 95,248 unique mothers and 49,189 unique fathers. The 100,778 pregnancies involved a total of 101,779 fetuses and resulted in 100,148 live births. The coverage of children in 2013 (the number of live births registered in JECS divided by the number of all live births within the study areas) was approximately 45%. Nevertheless, the data on the characteristics of the mothers and children we studied showed marked similarity to those obtained from Japan’s 2013 Vital Statistics Survey. Conclusions Between 2011 and 2014, we established one of the largest birth cohorts in the world.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Methodology
                Role: Supervision
                Role: SupervisionRole: Validation
                Role: SupervisionRole: Validation
                Role: SupervisionRole: Validation
                Role: SupervisionRole: Validation
                Role: SupervisionRole: Validation
                Role: SupervisionRole: Validation
                Role: SupervisionRole: Validation
                Role: SupervisionRole: Validation
                Role: SupervisionRole: Validation
                Role: SupervisionRole: Validation
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 January 2021
                2021
                : 16
                : 1
                : e0245782
                Affiliations
                [1 ] Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan
                [2 ] Department of Social Medicine, National Research Institute for Child Health and Development, Tokyo, Japan
                [3 ] Medical Support Center for the Japan Environment and Children’s Study, National Center for Child Health and Development, Tokyo, Japan
                [4 ] Division of Biostatistics, Department of Data Management, Center for Clinical Research, National Center for Child Health and Development, Tokyo, Japan
                [5 ] Allergy Center, National Center for Child Health and Development, Tokyo, Japan
                National Cancer Center, Japan, JAPAN
                Author notes

                Competing Interests: All the authors declare that they have no conflicts of interest associated with the publication of this research.

                ¶ Membership of the Japan Environment and Children’s Study (JECS) Group is listed in the Acknowledgments.

                Author information
                https://orcid.org/0000-0003-0997-2845
                https://orcid.org/0000-0002-0934-8949
                Article
                PONE-D-20-22340
                10.1371/journal.pone.0245782
                7842951
                33507986
                e0600b4c-99fe-4391-a596-95b62e9b9a04
                © 2021 Ogawa et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 July 2020
                : 7 January 2021
                Page count
                Figures: 1, Tables: 3, Pages: 14
                Funding
                The JECS was funded by the Ministry of the Environment, Japan. The findings and conclusions of this article are solely the responsibility of the authors and do not represent the official views of the Japanese government.
                Categories
                Research Article
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Immunology
                Allergies
                Allergic Diseases
                Food Allergies
                Biology and Life Sciences
                Immunology
                Clinical Immunology
                Allergies
                Allergic Diseases
                Food Allergies
                Medicine and Health Sciences
                Immunology
                Clinical Immunology
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                Custom metadata
                Data are unsuitable for public deposition due to ethical restrictions and legal framework of Japan. It is prohibited by the Act on the Protection of Personal Information (Act No.57 of 30 May 2003, amendment on 9 September 2015) to publicly deposit the data containing personal information. Ethical Guidelines for Epidemiological Research enforced by the Japan Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare also restricts the open sharing of the epidemiologic data. All inquiries about access to data should be sent to: jecs-en@ 123456nies.go.jp . The person responsible for handling enquiries sent to this e-mail address is Dr Shoji F. Nakayama, JECS Programme Office, National Institute for Environmental Studies.

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