Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions

Abigail Podany, Jessica Rauchut, Tong Wu, Yuka Imamura, Justin Wright, Regina Lamendella, David Soybel, Shannon L. Kelleher

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article number1800947
JournalMolecular Nutrition and Food Research
Volume63
Issue number3
DOIs
StatePublished - Feb 1 2019

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Zinc
neonates
Oxidative Stress
oxidative stress
zinc
genes
Genes
Immune System Phenomena
Pseudomonadales
Biological Phenomena
Gene Ontology
Campylobacter
Goblet Cells
goblet cells
Microbiota
Mucus
Ecology
mucus
Intestines
adhesion

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science

Cite this

Podany, Abigail ; Rauchut, Jessica ; Wu, Tong ; Imamura, Yuka ; Wright, Justin ; Lamendella, Regina ; Soybel, David ; Kelleher, Shannon L. / Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions. In: Molecular Nutrition and Food Research. 2019 ; Vol. 63, No. 3.
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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.",
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Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions. / Podany, Abigail; Rauchut, Jessica; Wu, Tong; Imamura, Yuka; Wright, Justin; Lamendella, Regina; Soybel, David; Kelleher, Shannon L.

In: Molecular Nutrition and Food Research, Vol. 63, No. 3, 1800947, 01.02.2019.

Research output: Contribution to journalArticle

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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 - Imamura, Yuka

AU - Wright, Justin

AU - Lamendella, Regina

AU - Soybel, David

AU - Kelleher, Shannon L.

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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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