TY - JOUR
T1 - Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions
AU - Podany, Abigail
AU - Rauchut, Jessica
AU - Wu, Tong
AU - Kawasawa, Yuka Imamura
AU - Wright, Justin
AU - Lamendella, Regina
AU - Soybel, David I.
AU - Kelleher, Shannon L.
N1 - Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
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U2 - 10.1002/mnfr.201800947
DO - 10.1002/mnfr.201800947
M3 - Article
C2 - 30513548
AN - SCOPUS:85058332354
SN - 1613-4125
VL - 63
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 3
M1 - 1800947
ER -