Xiaoyan Wang, Ting Yuan, Muhammad Asif Arain, Mohammed Al‐Rasheed, Aftab Shaukat
Heat stress (HS) remains a critical environmental constraint threatening the sustainability and productivity of global livestock and poultry production by including oxidative damage, compromising gut integrity, and disruption of immune homeostasis. The limited conventional nutritional strategies in conferring long-term thermotolerance underscore the urgent need for innovative and biologically effective interventions. In this context, phytobiotics, bioactive plant-derived compounds, have emerged as promising nutrigenomic modulators due to their potent antioxidant, anti-inflammatory, antimicrobial, and gut-protective properties, which collectively reinforce cellular defense mechanisms and enhance physiological adaptability under thermal challenge. This review provides a novel nutrigenomic perspective by elucidating how phytobiotics regulate the expression of key stress-responsive molecular pathways, including heat shock proteins (HSPs), nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinases (MAPKs), which govern oxidative balance, immune signaling, and apoptosis. Importantly, these mechanistic insights are reinforced by emerging in silico approaches, such as molecular docking and network pharmacology, which offer predictive validation of phytobiotic bioactivity, binding affinities, and target specificity against stress-related biomarkers, thereby accelerating the identification of high-potential candidates. By integrating experimental and computational evidence, this review consolidates current knowledge on the genomic and physiological roles of phytobiotics in mitigating HS and associated pathophysiological disturbances, and provides an effective scientific framework for the development of sustainable, phytobiotic-based nutritional strategies to enhance resilience and productivity in climate-vulnerable animal production systems.