Weaning Stress Aggravates Defense Response and the Burden of Protein Metabolism in Low-Birth-Weight Piglets

The effect of low birth weight (LBW) on piglet development has been widely demonstrated. However, the reasons for the significant decline in the growth performance of LBW piglets after weaning remain poorly understood. This study aimed to investigate the underlying mechanisms of this phenomenon. At 21 days of age, 24 normal-birth-weight (NBW) piglets and 24 LBW piglets were selected and divided into four groups-NBW control, NBW weaning, LBW control, and LBW weaning-with 12 replicates per group (1 piglet per replicate). Control groups were euthanized on the same day, while weaning groups were weaned and sampled 3 days later. The results showed that the body weight of NBW piglets increased, whereas that of LBW piglets decreased, after 3 days of weaning. Compared with NBW piglets, LBW piglets exhibited higher serum cortisol concentrations and lower villus height (<i>p</i> < 0.05). Weaning stress significantly increased serum cortisol and C-reactive protein concentrations in NBW piglets (<i>p</i> < 0.05), while no significant changes were observed in LBW piglets. However, weaning stress significantly increased serum blood urea nitrogen (BUN) concentrations (<i>p</i> < 0.05) in LBW piglets but not in NBW piglets. Additionally, weaning stress reduced the mRNA expressions of <i>Occludin</i>, <i>Claudin-1</i>, and <i>Claudin-2</i> in the jejunum of NBW piglets (<i>p</i> < 0.05), as well as <i>Occludin</i> in the jejunum of LBW piglets (<i>p</i> < 0.05). Furthermore, weaning stress reduced the mRNA expressions of <i>IL-6</i>, <i>TLR9</i>, <i>MyD88</i>, <i>TRIF</i> and <i>p65 NF-κB</i> in the jejunum of NBW piglets (<i>p</i> < 0.05). In LBW piglets, weaning stress decreased the mRNA expressions of <i>IL-2</i>, <i>TNF-α</i>, <i>NLRP3</i>, <i>TLR9</i>, and <i>NOD2</i> (<i>p</i> < 0.05). In conclusion, compared to NBW piglets, LBW piglets are more susceptible to weaning stress-induced protein metabolic disorders and intestinal barrier dysfunction, ultimately leading to impaired immune function and reduced growth performance. The results underscore the importance of tailored management strategies for piglets based on birth weight to mitigate weaning stress impacts.