Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions. Issue 3 (12th December 2018)

• Record Type: Journal Article
• Authors: Podany, Abigail; Rauchut, Jessica; Wu, Tong; Kawasawa, Yuka Imamura; Wright, Justin; Lamendella, Regina; Soybel, David I.; Kelleher, Shannon L.
• Is Part Of: Molecular nutrition & food research. Volume 63:Issue 3(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-12-12
• Subjects: host–microbe interactions -- infancy -- microbiome -- zinc; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201800947
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : Scope: Greater than 68% of young infants are exposed to dietary zinc (Zn) levels that are higher than the Tolerable Upper Intake Limit. However, the consequences of excess dietary Zn during early life on intestinal function and host–microbe interactions are unknown. Methods and Results: Neonatal mice are gavaged with 100 Zn µg d –1 from postnatal day (PN) 2 through PN10 and indices of intestinal function and host–microbe interactions are compared to unsupplemented mice. Excess dietary Zn causes oxidative stress, increases goblet cell number and mucus production, and are associated with increased intestinal permeability and systemic inflammation. Over 900 genes are differentially expressed; 413 genes display a fold‐change >1.60. The Gene Ontology Biological processes most significantly affected include biological adhesion, the immune system, metabolic processes, and response to stimulus. Key genes most highly and significantly upregulated include ALDH2, MT1, TMEM6, CDK20, and COX62b, while CALU, ST3GAL4, CRTC2, SLC28A2, and COMMA1 are downregulated. These changes are associated with a microbiome enriched in pathogenic taxa including Pseudomonadales and Campylobacter, and greater expression of bacterial stress response genes. Conclusion: Excess dietary Zn may have unforeseen influences on epithelial signaling pathways, barrier function, and luminal ecology in the intestine that may have long‐term consequences on intestinal health. Abstract : Excessive intake of dietary zinc is common in infants. In neonatal mice, excess dietary zinc causes oxidative stress in the intestine, which is associated with increased mucus production, intestinal permeability, and profound shifts in the microbiome. Moreover, changes in the expression of key intestinal genes implicated in metabolic processes, cytoskeletal arrangement, oxidative and ER stress, and protein glycosylation are identified, revealing novel molecular pathways that are affected by excess zinc intake.