Abstract The intestine adapts rapidly in early life to meet environmental and nutritional demands. While these changes aid short-term survival, they can program long-term gut function with consequences for growth and productivity. Although swine weaning practices are well studied for barrier disruption and inflammation, the impact of weaning age on later intestinal functions—especially nutrient sensing and transport—remains unclear. We hypothesized that early weaning stress alters epithelial composition and maturation, shifting nutrient digestion and absorption with lasting detrimental effects. Our objective was to determine how weaning age influences intestinal expression of key targets and functions involved in nutrient sensing, digestion, and transport. Twenty female piglets were weaned at day 15 (early, EW) or day 25 (late, LW), co-housed, and euthanized on day 35 to assess chronic, age-matched intestinal adaptations. Distal ileum was studied in Ussing chambers to measure active ion transport (short-circuit current, Isc) and electrogenic nutrient transport (ΔIsc to luminal glucose, dipeptide, alanine, lysine, and glutamine). Peptide YY (PYY) was quantified by ELISA in serum, ileal mucosa, and Ussing-chamber tissues. Ileal mucosa was analyzed for stem (BMI1), proliferative (SOX9), and secretory (HES1) markers; epithelial lineage markers—enterocyte (ALPi), goblet (MUC2), enteroendocrine (CHGA), and Paneth (LYZ); and a digestion/sensing/transport gene panel (PYY, GPR119, GPR120, FFAR1, FFAR3, LEAP2, T1R1, SI, PEPT1, ATP1A1, LAT1) by RT-qPCR. Digestive enzyme activities (sucrase, maltase, aminopeptidase) were assayed in mucosa and brush-border membrane vesicles. Group differences between EW and LW were tested by two-tailed Student’s t-test. EW pigs showed a trend toward higher basal Isc (greater Cl⁻ secretion; P 0.10). This profile coincided with upregulated BMI1 (damage-responsive stem cell marker), reduced SOX9, and increased HES1, with higher MUC2 (goblet cells) and lower LYZ (Paneth cells) (P 0.05), collectively indicating epithelial injury and inflammation. Under these conditions, Na+-dependent alanine and lysine transport (ΔIsc) decreased, whereas dipeptide transport increased significantly. EW pigs also exhibited higher maltase and aminopeptidase activities (P 0.05), consistent with upregulated SI, PEPT1, and ATP1A1 expression. Nutrient-sensing receptors GPR120 and FFAR1 were downregulated, while the anti-appetite gene LEAP2 was upregulated (P 0.05). Despite higher PYY mRNA, PYY secretion (serum and Ussing-chamber) was significantly reduced in EW pigs (P 0.05). Early-weaned piglets undergo intestinal reprogramming toward a prosecretory ileal phenotype and a more energy-efficient nutrient transport strategy as a compensatory adaptation to epithelial damage and inflammation. By enhancing digestion, dampening nutrient-sensing signals, and shifting amino-acid uptake toward peptide transport, the intestine rebalances nutrient acquisition under stress. Defining how early-life stress programs these pathways may guide strategies to improve feed efficiency in swine production.
Zhaoyan Zhu (Wed,) studied this question.
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