{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:47:14Z","timestamp":1784908034073,"version":"3.55.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Sepsis, a global health challenge, necessitates a nuanced understanding of modifiable factors for effective prevention and intervention. The role of trace micronutrients in sepsis pathogenesis remains unclear, and their potential connection, especially with genetic influences, warrants exploration.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We employed Mendelian randomization (MR) analyses to assess the causal relationship between genetically predicted blood levels of nine micronutrients (calcium, \u03b2-carotene, iron, magnesium, phosphorus, vitamin C, vitamin B6, vitamin D, and zinc) and sepsis susceptibility, severity, and subtypes. The instrumental variables for circulating micronutrients were derived from nine published genome-wide association studies (GWAS). In the primary MR analysis, we utilized summary statistics for sepsis from two independent databases (UK Biobank and FinnGen consortium), for initial and replication analyses. Subsequently, a meta-analysis was conducted to merge the results. In secondary MR analyses, we assessed the causal effects of micronutrients on five sepsis-related outcomes (severe sepsis, sepsis-related death within 28\u00a0days, severe sepsis-related death within 28\u00a0days, streptococcal septicaemia, and puerperal sepsis), incorporating multiple sensitivity analyses and multivariable MR to address potential heterogeneity and pleiotropy.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The study revealed a significant causal link between genetically forecasted zinc levels and reduced risk of severe sepsis-related death within 28\u00a0days (odds ratio [OR] = 0.450; 95% confidence interval [CI]: 0.263, 0.770; <jats:italic>p<\/jats:italic> = 3.58 \u00d7 10<jats:sup>\u22123<\/jats:sup>). Additionally, suggestive associations were found for iron (increased risk of sepsis), \u03b2-carotene (reduced risk of sepsis death) and vitamin C (decreased risk of puerperal sepsis). No significant connections were observed for other micronutrients.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our study highlighted that zinc may emerges as a potential protective factor against severe sepsis-related death within 28\u00a0days, providing theoretical support for supplementing zinc in high-risk critically ill sepsis patients. In the future, larger-scale data are needed to validate our findings.<\/jats:p>","DOI":"10.3389\/fgene.2024.1353118","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T04:50:49Z","timestamp":1708059049000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Circulating micronutrient levels and their association with sepsis susceptibility and severity: a Mendelian randomization study"],"prefix":"10.3389","volume":"15","author":[{"given":"Zhengxiao","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingfen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuhong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1080\/13685538.2020.1740200","article-title":"Serum trace element and heavy metal levels in patients with sepsis","volume":"23","author":"Akkas","year":"2020","journal-title":"Aging Male"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e649","DOI":"10.1097\/MJT.0000000000001423","article-title":"Vitamin C for sepsis and septic shock","volume":"28","author":"Ammar","year":"2021","journal-title":"Am. 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