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PSVI-9 Temporal transcriptional and functional dynamics of small intestine mucosal response to early weaning in piglets.

Year: 2025
Type: article
Abstract: Early weaning in swine production imposes significant psychosocial and environmental stress during a critical window of gastrointestinal (GI) development. While this practice maximizes sow reproductive efficiency, early weaning has been shown to profoundly disrupt GI development, altering the intestinal epithelial barrier, reshaping immune function, and inducing lasting changes in the enteric nervous system. Despite these adverse outcomes, the early molecular mechanisms that initiate these alterations and set the gut on a divergent developmental trajectory remain poorly understood. To address this knowledge gap, this study aims to identify the earliest transcriptional and functional changes in the gut immediately following weaning, capturing distinct phases of gene expression that may drive an altered developmental course. Sixteen male castrated Yorkshire-Duroc piglets were divided into three groups for tissue collection: unweaned (0 h), 3 hours post-weaning, and 24 hours post-weaning, with the latter two groups weaned at 16-18 days of age. The 3-hour time point was selected with the goal of capturing immediate early-response genes, which reflect acute stress signaling and transcriptional regulators, while the 24-hour time point was aimed to capture sustained transcriptional changes leading to long-term physiological adaptations. We utilized RNA sequencing, followed by comprehensive bioinformatic analyses, to delineate the early transcriptional profile of the jejunal mucosa in early weaned male castrates compared to their unweaned littermates. Ex vivo Ussing chamber experiments were performed to validate the functional changes associated with the observed transcriptional alterations. We show that weaning triggers rapid transcriptional changes in the GI tract, observable as early as 3 hours post-weaning. At 3 hours post-weaning, we observed differential expression in 1,605 genes (776 upregulated, 829 downregulated; un-adjusted P-value ≤ 0.05). By 24 hours, this increased to 3,338 differentially expressed genes (1,469 upregulated, 1,849 downregulated). These include reduced expression of mitochondrial energy production genes and increased expression of glucose transporters. Weaning activates pathways associated with ion channel transport (BH-adjusted P-value < 0.05), including KCN, SCN, TRP, and SLC gene families and genes encoding neurotransmitter receptors such as cholinergic, dopaminergic, GABAergic, and glutamatergic receptors. While these are key pathways influenced by weaning, additional pathways—including keratinization, ribosomal function, and cholesterol biosynthesis—also exhibit significant transcriptional changes during this developmental transition. Ex vivo electrophysiological experiments revealed increased SGLT-mediated glucose transport (P=0.015) and enhanced neural-evoked secretory function (P < 0.0001) in weaned pigs 24 hours post-weaning, supporting the gene pathway analyses. Overall, our findings highlight key pathways—neuronal signaling, ion transport, and nutrient absorption—that are prominently activated in response to weaning. These pathways provide potential targets for interventions to mitigate the long-term consequences of weaning-associated stressors.
DOI: 10.1093/jas/skaf300.476
Language: English
Open Access status: bronze
OpenAlex ID: W4414831183
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