Host genomic regulation of gut microbiota resilience under environmental stress in pigs

Climate change and intensive genetic selection for greater productivity have increased the need for breeding livestock with better adaptive capacity, supported by microbiome–host interactions that promote resilience. The gut microbiota plays a key role in maintaining host homeostasis under thermal and oxidative stress, yet the genomic regulation underlying microbiota resilience remains poorly understood. In this context, the main objective of this study was to investigate host genetic variants associated with bacterial genera linked to adaptive and metabolic resilience in pigs. A genome-wide association study (GWAS) was performed using genotypes from a commercial 50K SNP chip and microbial profiles obtained by 16S rRNA sequencing of cecal and fecal samples (ASV level, 10% prevalence). These data were integrated with expression quantitative trait loci (eQTL) derived from RNA-seq (TPM-normalized) across brain, liver, and muscle tissues of 72 immunocastrated Large White males fed diets containing soybean, fish, or canola oil. Both cis (≤1 Mb) and trans (>1 Mb) eQTL were considered (FDR < 0.05). Thirty-seven bacterial genera were associated with eQTL, among which Monoglobus, Intestinimonas, Fournierella, Helicobacter, Coprococcus, Anaerostipes, Faecalibacterium, Roseburia, and Oscillospira were linked to metabolic and physiological pathways that support host resilience. These include short-chain fatty acid metabolism, mucin utilization, immune modulation, and neuroendocrine regulation. Most associations involved fecal microorganisms linked to trans-eQTL in the brain. Thirty-eight host genes were identified across cis- and trans-regulatory regions. Associated loci covered genes involved in epithelial barrier integrity and mucosal protection, including tight junction claudins (CLDN17 locus) and TFF2, as well as stress-response candidates such as CASP2, indicating a genomic contribution to microbiota-mediated resilience under environmental challenges. The identified microbial groups play a crucial role in maintaining metabolic stability and intestinal homeostasis during physiological challenges, suggesting that host regulation of microbial diversity may help sustain good welfare and adaptive capacity in intensive production environments.