Immune stress markedly affects the immune function and growth performance of livestock, including poultry, resulting in financial loss to farmers. It can lead to decreased feed intake, reduced growth, and intestinal disorders. Studies have shown that pathogen-induced immune stress is mostly related to TLR4-related inflammatory signal pathway activation, excessive inflammatory cytokine release, oxidative stress, hormonal disorders, cell apoptosis, and intestinal microbial disorders. This paper reviews the occurrence of immune stress in livestock, its impact on immune function and growth performance, and strategies for immune stress prevention.

Herein, we assessed the anti-inflammatory and intestinal barrier protective effects of butyrolactone-I (BTL-1), derived from the coral-derived endophytic fungus (Aspergillus terreus), using the LPS-induced IPEC-J2 inflammation model and the DSS-induced IBD model in mice. In IPEC-J2 cells, pretreatment with BTL-I significantly inhibited TLR4/NF-κB signaling pathway and JNK phosphorylation, resulting in the decrease of IL-1β and IL-6 expression. Interestingly, BTL-1 pretreatment activated the phosphorylation of ERK and P38, which significantly enhanced the expression of TNF-α. Meanwhile, BTL-1 pretreatment upregulated tight junction protein expression (ZO-1, occludin, and claudin-1) and maintained intestinal barrier and intestinal permeability integrity. In mice, BTL-1 significantly alleviated the intestinal inflammatory response induced by DSS, inhibited TLR4/NF-κB signaling pathway, and MAPK signaling pathway, thus reducing the production of IL-1, IL-6, and TNF-α. Further, the expression of tight junction proteins (ZO-1, occludin, and claudin-1) was upregulated in BTL-1 administrated mice. Therefore, it has been suggested that butyrolactone-I alleviates inflammatory responses in LPS-stimulated IPEC-J2 and DSS-induced murine colitis by TLR4/NF-κB and MAPK signal pathway. Thereby, BTL-1 might potentially be used as an ocean drug to prevent intestinal bowel disease.

Heat stress poses a significant challenge to animal husbandry, contributing to oxidative stress, intestinal mucosal injury, and apoptosis, which severely impact animal health, growth, and production efficiency. The development of safe, sustainable, and naturally derived solutions to mitigate these effects is critical for advancing sustainable agricultural practices. Butyrolactone-I (BTL-I), a bioactive compound derived from deep-sea fungi (Aspergillus), shows promise as a functional feed additive to combat heat stress in animals. This study explored the protective effects of BTL-I against heat-stress-induced oxidative stress and apoptosis in IPEC-J2 cells and mice. Our findings demonstrated that BTL-I effectively inhibited the heat-stress-induced upregulation of HSP70 and HSP90, alleviating intestinal heat stress. Both in vitro and in vivo experiments revealed that heat stress increased intestinal cell apoptosis, with a significant upregulation of Bax/Bcl-2 expression, while BTL-I pretreatment significantly reduced apoptosis-related protein levels, showcasing its protective effects. Furthermore, BTL-I suppressed oxidative stress markers (ROS and MDA) while enhancing antioxidant activity (SOD levels). BTL-I also reduced the expression of p-PERK, p-eIF2α, ATF4, and CHOP, mitigating oxidative and endoplasmic reticulum stress in intestinal cells. In conclusion, BTL-I demonstrates the potential to improve animal resilience to heat stress, supporting sustainable livestock production systems. Its application as a natural, eco-friendly feed additive will contribute to the development of sustainable agricultural practices.