Integrative hologenomic analysis reveals apolipoprotein D–associated host–microbe metabolic crosstalk linked to fat deposition in Jinhua pigs

Abstract

Background Adipose deposition is a complex trait shaped by both host genetics and environmental factors, including the gut microbiota. While quantitative trait loci (QTLs) and candidate genes underlying fat accumulation have been extensively identified in diverse pig breeds, the hologenomic regulatory networks integrating host genetic variation and microbial signals remain to be fully deciphered. Methods In this study, we utilized a strictly controlled dietary cross-fostering model involving Jinhua and Landrace×Yorkshire pigs across developmental stages (day60, day90 and day180). We integrated population genetics, eQTL analysis, transcriptomics, metagenomics and metabolomics to elucidate the host-metabolite-microbe axis. Results Phenotypic analysis revealed a robust genetic trait for high backfat thickness in Jinhua pigs, independent of dietary intervention. Through FST analysis and eQTL mapping, we pinpointed a strongly differentiated locus (13_133481393_A_G) that was nearly fixed in JH pigs (allele frequency 0.95) and was associated with upregulation of APOD. In our multi-omics dataset, this locus was linked to shifts in cecal gene expression that were consistent with a pro-adipogenic program, which coincided with an intestinal metabolic profile marked by elevated oleic acid and reduced oleoylethanolamide. This metabolic niche, in turn, directionally recruited synergistic microbes, specifically Eubacterium sp. AM28-29 and Blautia, which functioned as biochemical amplifiers to further accelerate lipid accumulation. Conclusion Our study establishes a hologenomic framework demonstrating how foundational genetic selection (APOD) shapes the host-microbe metabolic interplay to drive complex production traits. This study offers novel molecular targets and a theoretical framework for precision breeding and nutritional modulation of meat quality in livestock.