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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. [ABSTRACT FROM AUTHOR]

Although numerous studies have shown that the hypothalamic–pituitary–adrenal axis plays a vital role in the response to environmental stress by mediating the production of a series of hormones, the mechanism underlying these effects has not been elucidated. This study used proteomics techniques to investigate the differentially expressed proteins (DEPs) in the pituitary glands of pigs and to elucidate the potential changes in the immune–neuroendocrine system under heat stress (HS). In total, 2517 peptides corresponding to 205 proteins were detected. A comparison of the expression patterns between HSs and healthy controls revealed 56 DEPs, of which 31 were upregulated and 25 were downregulated. Ingenuity pathway analysis (IPA) was used to reveal the subcellular characteristics, functional pathways, regulatory networks, and upstream regulators of the identified proteins. The results showed that these differentially expressed proteins were involved in intercellular communication, interactions, apoptosis, nervous system development, functions, abnormalities and other functions, and in the regulatory network. Moreover, the upstream regulators of the differentially expressed proteins were mainly transcriptional regulators, hormones, and cytokines. Thus, the functional network and pathway analyses could provide insights into the complexity and dynamics of HS–host interactions and may accelerate our understanding of the mechanisms underlying HS. [ABSTRACT FROM AUTHOR]

Heat stressed pigs show typical characteristics of inflammatory bowel disease (IBD). However, little is known about the pathogenesis of heat stress (HS)-induced IBD in pigs. In this study, we determined the effects of HS on colon morphology, intestinal microbiota diversity, transcriptome genes (transcripts), and short chain fatty acids (SCFAs) metabolism in pigs. In addition, the correlation among these parameters was analyzed by weighted gene co-expression network analysis. Results showed that the liver and kidney functions related to blood biochemical indexes were partially changed in pigs under HS. Furthermore, the levels of diamine oxidase and D-lactic acid were significantly increased, whereas the levels of secretory immunoglobulin A were decreased. The integrity of colonic tissue was damaged under HS, as bleeding, lymphatic infiltration, and villi injury were observed. The concentrations of SCFAs in the colon, such as acetic acid and butyric acid, were decreased significantly. In addition, the composition of colon microbiota, such as decrease in Lactobacillus johnsonii , Lactobacillus reuteri and increase in Clostridium sensu stricto 1 of day 7 and 14 while under HS. These changes were associated with changes in the concentration of SCFAs and biochemical indexes above mentioned. Differentially expressed genes were enriched in the nucleotide-binding oligomerization domain-like receptor signaling pathway, Th17 cell differentiation, and IBD pathway, which were also associated with the changes in SCFAs. Thus, the structure, diversity of intestinal microorganisms, and changes in the levels of SCFAs in colon of heat stressed pigs changed significantly, contributing to the activation of immune response and inflammatory signal pathways and causing abnormal physiological and biochemical indexes and intestinal mucosal damage. These results highlight the interconnections between intestinal microbiota, SCFAs, and immune response and their role in the pathogenesis of stress induced IBD therapy. [ABSTRACT FROM AUTHOR]

Heat stress (HS) has a negative impact on animal health. A modified chitosan-gentamicin conjugate (CS-GT) was prepared to investigate its potential protective effects and mechanism of action on heat stress-induced intestinal mucosa injury in IPEC-J2 cells and mouse 3D intestinal organs in a mouse model. CS-GT significantly (P < 0.01) reversed the decline in transmembrane resistance and increased the FITC-dextran permeability of the IPEC-J2 monolayer fusion epithelium caused by heat stress. Heat stress decreased the expression of the tight binding proteins occludin, claudin1, and claudin2. However, pretreatment with CS-GT significantly increased (P < 0.01) the expression of these tight binding proteins. Mechanistically, CS-GT inhibited the activation of the TLR4/STAT6/MYLK signaling pathway induced by heat stress. Molecular docking showed that CS-GT can bind effectively with TLR4. In conclusion, CS-GT alleviates heat stress-induced intestinal mucosal damage both in vitro and in vivo. This effect is mediated, at least partly, by the inhibition of the TLR4/STAT6/MYLK signaling pathway and upregulation of tight junction proteins. These findings suggest that CS-GT may have therapeutic potential in the prevention and treatment of heat stress-related intestinal injury. [Display omitted] [ABSTRACT FROM AUTHOR]

In many mammalian species, including pigs, heat stress (HS) detrimentally leads to epithelium damage and increases intestinal permeability. However, the underlying molecular mechanisms are not thoroughly investigated yet. This study aimed to examine the RIP1/RIP3-ERK1/2 signaling pathway that regulates the expression of tight junction proteins in HS-treated pigs. In in vitro cultured intestinal porcine epithelial cells (IPEC-J2), HS induced the expression of tight junction proteins, ZO-1, claudin-1, and claudin-4, that are regulated by the ERK1/2-MAPK signaling pathway. Further, high expression of HSP70 in IPEC-J2 cells induced a significant decrease in receptor-interacting protein 1/3 (RIP1/3), phosphorylated ERK, and tight junction protein claudin-1 (P < 0.05). Necrostatin-1 (A selective inhibitor of RIPK1) suppressed the upregulation of phosphorylated ERK1/2 induced by HS, indicating that the RIP1/RIP3 regulates ERK1/2 phosphorylation in IPEC-J2 under heat stress. In addition, HS significantly damaged the intestinal morphology characterized by reduction of villus length and crypt depth in in vivo porcine model. Moreover, the expression of tight junction, ZO-1, and claudin-4 were downregulated, whereas phosphorylated p38 and ERK1/2 were upregulated in the duodenum of heat-stressed pigs. Interestingly, a decrease in ZO-1 and claudin-1 was observed in the colon, where phosphorylated ERK1/2 was similar to that in the duodenum. Our results demonstrate that RIP1/RIP3-ERK1/2 signaling pathway regulates the expression of tight junction proteins in HS-pigs. This finding further advances the intestinal barrier function's underlying mechanisms associated with signaling regulation. • A heat stress induced porcine inflammatory bowel disease model was constructed successfully. • Heat stress induced down – regulation of tight junction proteins play a vital role in the development inflammatory bowel disease in pigs. • Heat stress induced down-regulation of tight junction proteins was via ERK1/2 signaling pathway. [ABSTRACT FROM AUTHOR]