Gut–brain axis disruption sustains low intake syndrome in weanling pigs

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 performance. 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 a proxy for individual feed intake (n = 12/timepoint).

RNA sequencing of ileal and hypothalamic tissue revealed that low‑ADG pigs at day 7 exhibited impaired intestinal barrier function, suppressed metabolic and immune pathways, and hypothalamic activation of appetite‑suppressing (mTORC1, GLP‑1) and thermogenic signalling, together with endocrine disruption. By day 39, digestive and metabolic pathways were upregulated in the ileum of low‑ADG pigs, yet gut integrity deficits persisted alongside sustained hypothalamic immune activation and disrupted appetite signalling.