Longitudinal Multi-omics Profiling Reveals Different Adaptation to Heat Stress in Genomically Divergent Lactating Sows

Background. Heat stress (HS) poses a growing threat to health and productivity across mammals, a problem exacerbated by climate change. Simultaneously, the gut microbiome plays a crucial role in host adaptation to environmental stressors, yet the molecular mechanisms underlying microbiome-mediated heat tolerance remain poorly understood. Although multi-omics profiling has recently emerged as a powerful tool to explore host–microbiome interactions, no prior study, to our knowledge, has simultaneously integrated metagenomics, metatranscriptomics, and metabolomics in genetically characterized lactating mammals under HS conditions. Here, we present a time-resolved, multi-omics analysis of genomically divergent sows (heat-tolerant, TOL, and heat-sensitive, SEN) exposed to controlled HS, with the aim of identifying microbial and metabolic signatures of resilience. Results. Metagenomic analyses revealed enrichment of specific taxa in TOL sows, including Treponema , F23-B02 , and Bifidobacterium , with both enduring and time-specific effects. Metatranscriptomic profiling uncovered functional reprogramming in carbohydrate metabolism, membrane remodeling, and oxidative stress responses in TOL animals. These findings were further supported by metabolomic signatures indicating alterations in lipid turnover, amino acid metabolism, and redox homeostasis. Finally, integration of multi-omics data highlighted coordinated, time-specific microbial responses in TOL sows, reflecting robust host–microbiome adaptations to HS. Conclusions. By identifying candidate microbial biomarkers and conserved functional pathways, this study provides new insights into mammalian HS resilience and establishes a framework for cross-species investigations into heat resilience, stress physiology, and microbiome-targeted interventions.