Enterocyte-specific deletion of metal transporter Zip14 (Slc39a14) alters intestinal homeostasis through epigenetic mechanisms.

Zinc has anti-inflammatory properties using mechanisms that are unclear. Zip14 (Slc39a14) is a zinc transporter induced by proinflammatory stimuli and is highly expressed at the basolateral membrane of intestinal epithelial cells (IECs). Enterocyte-specific Zip14 ablation (Zip14ΔIEC) in mice was developed to study the functions of this transporter in enterocytes. This gene deletion led to increased intestinal permeability, increased IL-6 and IFNγ expression, mild endotoxemia, and intestinal dysbiosis. RNA sequencing was used for transcriptome profiling. These analyses revealed differential expression of specific intestinal proinflammatory and tight junction (TJ) genes. Binding of transcription factors, including NF-κß, STAT3, and CDX2, to appropriate promoter sites of these genes supports the differential expression shown with chromatin immunoprecipitation assays. Total histone deacetylase (HDAC), and specifically HDAC3, activities were markedly reduced with Zip14 ablation. Intestinal organoids derived from ΔIEC mice display TJ and cytokine gene dysregulation compared with control mice. Differential expression of specific genes was reversed with zinc supplementation of the organoids. We conclude that zinc-dependent HDAC enzymes acquire zinc ions via Zip14-mediated transport and that intestinal integrity is controlled in part through epigenetic modifications.NEW & NOTEWORTHY We show that enterocyte-specific ablation of zinc transporter Zip14 (Slc39a14) results in selective dysbiosis and differential expression of tight junction proteins, claudin 1 and 2, and specific cytokines associated with intestinal inflammation. HDAC activity and zinc uptake are reduced with Zip14 ablation. Using intestinal organoids, the expression defects of claudin 1 and 2 are resolved through zinc supplementation. These novel results suggest that zinc, an essential micronutrient, influences gene expression through epigenetic mechanisms.

Pond bank access as an approach for managing toxic cyanobacteria in beef cattle pasture drinking water ponds.

Forty-one livestock drinking water ponds in Alabama beef cattle pastures during were surveyed during the late summer to generally understand water quality patterns in these important water resources. Since livestock drinking water ponds are prone to excess nutrients that typically lead to eutrophication, which can promote blooms of toxigenic phytoplankton such as cyanobacteria, we also assessed the threat of exposure to the hepatotoxin, microcystin. Eighty percent of the ponds studied contained measurable microcystin, while three of these ponds had concentrations above human drinking water thresholds set by the US Environmental Protection Agency (i.e., 0.3 µg/L). Water quality patterns in the livestock drinking water ponds contrasted sharply with patterns typically observed for temperate freshwater lakes and reservoirs. Namely, we found several non-linear relationships between phytoplankton abundance (measured as chlorophyll) and nutrients or total suspended solids. Livestock had direct access to all the study ponds. Consequently, the proportion of inorganic suspended solids (e.g., sediment) increased with higher concentrations of total suspended solids, which underlies these patterns. Unimodal relationships were also observed between microcystin and phytoplankton abundance or nutrients. Euglenoids were abundant in the four ponds with chlorophyll concentrations > 250 µg/L (and dominated three of these ponds), which could explain why ponds with high chlorophyll concentrations would have low microcystin concentrations. Based on observations made during sampling events and available water quality data, livestock-mediated bioturbation is causing elevated total suspended solids that lead to reduced phytoplankton abundance and microcystin despite high concentrations of nutrients, such as phosphorus and nitrogen. Thus, livestock could be used to manage algal blooms, including toxic secondary metabolites, in their drinking water ponds by allowing them to walk in the ponds to increase turbidity.