{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:25:13Z","timestamp":1760235913971,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill &amp; Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1150161"],"award-info":[{"award-number":["OPP1150161"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9\u201311 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies.<\/jats:p>","DOI":"10.3390\/nu13103516","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T21:26:20Z","timestamp":1633728380000},"page":"3516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children"],"prefix":"10.3390","volume":"13","author":[{"given":"Thomas","family":"Hayman","sequence":"first","affiliation":[{"name":"Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8153-6258","authenticated-orcid":false,"given":"Peter","family":"Hickey","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Advanced Technology and Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Amann-Zalcenstein","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Advanced Technology and Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9796-9381","authenticated-orcid":false,"given":"Cavan","family":"Bennett","sequence":"additional","affiliation":[{"name":"Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Ataide","sequence":"additional","affiliation":[{"name":"Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5988-358X","authenticated-orcid":false,"given":"Rahvia Alam","family":"Sthity","sequence":"additional","affiliation":[{"name":"International Centre for Diarrheal Disease Research, Nutrition and Clinical Services Division, Bangladesh (icddr,b), Dhaka 1212, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-6200","authenticated-orcid":false,"given":"Afsana Mim","family":"Khandaker","sequence":"additional","affiliation":[{"name":"International Centre for Diarrheal Disease Research, Nutrition and Clinical Services Division, Bangladesh (icddr,b), Dhaka 1212, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazi Munisul","family":"Islam","sequence":"additional","affiliation":[{"name":"International Centre for Diarrheal Disease Research, Nutrition and Clinical Services Division, Bangladesh (icddr,b), Dhaka 1212, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1291-6783","authenticated-orcid":false,"given":"Katharina","family":"Stracke","sequence":"additional","affiliation":[{"name":"Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nawaf","family":"Yassi","sequence":"additional","affiliation":[{"name":"Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"Melbourne Brain Centre, Departments of Medicine and Neurology, The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC 3050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosie","family":"Watson","sequence":"additional","affiliation":[{"name":"Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC 3050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Westcott","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy F.","family":"Krebs","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA"},{"name":"International Zinc Nutrition Consultative Group, University of California, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet C.","family":"King","sequence":"additional","affiliation":[{"name":"International Zinc Nutrition Consultative Group, University of California, San Francisco, CA 94158, USA"},{"name":"Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E.","family":"Black","sequence":"additional","affiliation":[{"name":"International Zinc Nutrition Consultative Group, University of California, San Francisco, CA 94158, USA"},{"name":"Institute for International Programs, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21218, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md. Munirul","family":"Islam","sequence":"additional","affiliation":[{"name":"International Centre for Diarrheal Disease Research, Nutrition and Clinical Services Division, Bangladesh (icddr,b), Dhaka 1212, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine M.","family":"McDonald","sequence":"additional","affiliation":[{"name":"International Zinc Nutrition Consultative Group, University of California, San Francisco, CA 94158, USA"},{"name":"Departments of Pediatrics and Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5502-0434","authenticated-orcid":false,"given":"Sant-Rayn","family":"Pasricha","sequence":"additional","affiliation":[{"name":"Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia"},{"name":"Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Diagnostic Haematology, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia"},{"name":"Clinical Haematology at the Peter MacCallum Cancer Centre, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wessells, K.R., and Brown, K.H. 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