Abstract
BACKGROUND: Intensive breeding system makes piglets expose to infectious agents causing immunological stress. Lipopolysaccharide (LPS), a material found in Gram-negative bacteria’s cell walls, can induce immunological stress. Some studies demonstrated that immunological stress was harmful to intestinal functions of piglets. Capsaicin (CAP) has been reported to improve intestinal functions both in vivo and in vitro experiments. Thus, this study’s objective was to look into whether CAP supplementation could be an effective mean to protect jejunum of piglets against immunological stress. RESULTS: The results showed that during the whole rearing period, 400 and 800 mg/kg CAP supplementation were able to reduce feed conversion ratio of piglets (P < 0.05), and 800 mg/kg CAP showed the best effect. LPS challenge contributed to impaired jejunal morphology, increased permeability of jejunum, occurrence of jejunal inflammation, and necroptosis of jejunal epithelial cells (P < 0.05). Nevertheless, CAP pretreatment elevated villus height and ratio of villus height to crypt depth in the jejunum of LPS-challenged piglets (P < 0.05). CAP intervention degraded serum diamine oxidase activity and D-lactate concentration of LPS-challenged piglets (P < 0.05). Administering CAP also increased jejunal lactase activity and the mRNA expression of zonula occludens-1 and occluding of LPS-challenged piglets (P < 0.05). CAP supplementation decreased serum interleukin (IL)-6 level and jejunal IL-1β levels of LPS-challenged piglets (P < 0.05). Meanwhile, CAP pretreatment downregulated the mRNA expression of toll-like receptor 4, myeloid differentiation factor 88, and nuclear factor-kappa B and the protein expression of integrin alpha M, while CAP pretreatment upregulated the mRNA expression of IL-10 in the jejunum of LPS-challenged piglets (P < 0.05). CAP supplementation reduced the expression of genes related to necroptosis and the protein expression of high mobility group box 1 in the jejunum of LPS-challenged piglets (P < 0.05). Moreover, CAP lowered the relative abundance of jejunal Acinetobacter of piglets challenged with LPS (P < 0.05). CONCLUSIONS: Dietary CAP supplementation improves growth performance of piglets before LPS challenge. Furthermore, CAP pretreatment could protect jejunum against immunological stress. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-026-05346-6.