Gut–brain axis alterations suggest a low feed intake syndrome in weanling pigs

Abrupt weaning imposes highly variable physiological stress on pigs, yet the mechanisms underlying this variability remain poorly understood. We applied an integrative approach combining transcriptomics, gastrointestinal phenotyping, and blood biomarkers to characterize gut–brain axis dynamics at one week post‑weaning (day 7) and at the end of the nursery phase (day 39) in pigs with divergent early ADG. Twenty‑four pigs of similar weaning weight (5.65 ± 1.0 kg) were selected from pens showing extreme early feed intake post-weaning and subsequently classified by average daily gain (ADG) as an early adaptation phenotype ( n = 12/timepoint). RNA sequencing identified 40 and 46 differentially expressed genes (DEGs) in the ileum and hypothalamus, respectively, at day 7, and 119 and 80 DEGs at day 39. Low-ADG pigs at day 7 exhibited transcriptional signatures consistent with impaired intestinal barrier integrity and nutrient metabolism-related pathways together with hypothalamic activation of immune and appetite-suppressing signalling. These changes were accompanied by higher insulin ( P = 0.020) and lower IGF-I ( P = 0.036) and TNF-α ( P = 0.016) concentrations. By day 39, digestive and metabolic pathways were upregulated in the ileum of Low-ADG pigs, whereas impaired gut integrity and altered hypothalamic signalling persisted. Low-ADG pigs also exhibited higher triglycerides ( P = 0.028), insulin ( P = 0.041), leptin ( P = 0.003), and TNF-α ( P = 0.035) concentrations, together with lower PYY ( P = 0.022). Collectively, these findings suggest a “low feed intake syndrome”, in which early nutrient deprivation, compromised gut integrity, and dysregulated neuroendocrine signalling converge to perpetuate poor growth and long‑term maladaptation.