The Znt7-null mutation has sex dependent effects on the gut microbiota and goblet cell population in the mouse colon

Authors: Kable, Mary; RIAZATI, NIKNAZ - University Of California, Davis; Kirschke, Catherine; ZHAO, JUNLI - Nanjing Xiaozhuang University; TEPAAMORNDECH, SURAPUN - National Center For Genetic Engineering And Biotechnology (BIOTEC); Huang, Liping

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/11/2020
Publication Date: 9/29/2020
Citation: Kable, M.E., Riazati, N., Kirschke, C.P., Zhao, J., Tepaamorndech, S., Huang, L. 2020. The Znt7-null mutation has sex dependent effects on the gut microbiota and goblet cell population in the mouse colon. PLoS ONE. 15(9). Article e0239681. https://doi.org/10.1371/journal.pone.0239681.
DOI: https://doi.org/10.1371/journal.pone.0239681

Interpretive Summary: Zinc is an essential element for living organisms. Zinc concentration and distribution within a given cell are tightly regulated by zinc transporters. The zinc transporter 7 (ZnT7) is enriched on the membrane of the Golgi complex (a machinery within the cell where proteins are matured and sorted to their destinations) of intestinal absorptive cells and goblet cells (mucin secreting cells). It has previously been shown that Znt7 knockout leads to zinc deficiency and decreased weight gain in C57Bl/6 mice on a defined diet. However, effects within the colon are unknown. Given the expression profile of Znt7, we set out to analyze the changes in mucin density and gut microbial composition in the mouse large intestine caused by Znt7 knockout. We fed a semi-puri'ed diet containing 30 mg Zn/kg to Znt7-null mice with their heterozygous (one intact and one null copy of Znt7 in the genome) and wild type (WT) littermates and found a sex specific effect on body weight, colonic mucin density, goblet cell number, and microbiome composition. In male mice, Znt7 knockout led to increased goblet cell number, but had little effect on mucin density or gut microbiome composition. However, in female mice, Znt7 knockout was associated with reduced mucin density, reduced goblet cell number, and increased proportions of the microbial taxa, Allobaculum, relative to WT. The gut microbial composition was correlated with mucin density in both sexes. These findings suggest that a sex-specific relationship exists between zinc physiological equilibrium, mucin production, and the microbial community composition within the colon.

Technical Abstract: Cellular homeostasis of zinc, an essential element for living organisms, is tightly regulated by a family of zinc transporters. The zinc transporter 7, ZnT7, is highly expressed on the membrane of the Golgi complex of intestinal epithelial cells and goblet cells. It has previously been shown that Znt7 knockout leads to zinc deficiency and decreased weight gain in C57BL/6 mice on a defined diet. However, effects within the colon are unknown. Given the expression profile of Znt7, we set out to analyze the changes in mucin density and gut microbial composition in the mouse large intestine induced by Znt7 knockout. We fed a semi-puri'ed diet containing 30 mg Zn/kg to Znt7-/- mice with their heterozygous and wild type littermates and found a sex specific effect on body weight, colonic mucin density, goblet cell number, and microbiome composition. In male mice Znt7 knockout led to increased goblet cell number, but had little effect on mucin density or gut microbiome composition. However, in female mice Znt7 knockout was associated with reduced mucin density, reduced goblet cell number and increased proportions of the microbial taxa, Allobaculum, relative to wild type. The gut microbial composition was correlated with mucin density in both sexes. These findings suggest that a sex-specific relationship exists between zinc homeostasis, mucin production and the microbial community composition within the colon.