Divergent jejunal cis- and trans-eQTLs and their microbiome associations following a diet lacking mineral phosphorus supplements in laying hens.

Abstract

Phosphorus (P) utilization is a complex trait influenced by numerous genetic variants. The jejunum is the primary site of P absorption in poultry. Therefore, identifying the genetics that regulate transcription in jejunum may help uncover key regulators of P homeostasis. We performed a genome-wide association study using the expression of jejunal mucosa transcripts (88 miRNAs, 65 mRNAs). These transcripts were selected from our previous studies due to their association with P utilization and related pathways. In total, the trial comprised 400 laying hens from two high-yielding strains, Lohmann Brown (LB) and Lohmann Selected Leghorn (LSL), fed a diet lacking mineral P supplements and exogenous microbial phytase to stimulate adaptive mechanisms. In total, 114 miR-eQTLs (microRNA expression quantitative trait loci) were detected at a false discovery rate (FDR) of less than 5%, including 56 miR-eQTLs in the LB strain and 58 miR-eQTLs in the LSL strain. Lohmann Brown contained 23 cis and 35 trans loci, with the most significant cis-eQTL targeting miR-146b. In the LSL strain, a cis-eQTL cluster for miR-203a was present on chromosome 5. Similarly, 123 mRNA-eQTLs (94 in LB and 29 in LSL) were identified at the 5% FDR threshold. The genetic regulation of key genes involved in mineral binding and mineral transport, including CALB1 and SLC34A2, in LB hens was predominantly driven by strong cis-eQTL. In contrast, gene expression in LSL hens was largely modulated by trans-eQTLs, with CALM1 being the only gene under significant cis-regulation. Furthermore, correlation analysis with the gut microbiome revealed that the expression of cis-regulated CALB1 is significantly positively associated with the abundance of Lactobacillus species. Our findings reveal that LB and LSL hens exhibit distinct genetic architectures contributing to maintain mineral homeostasis. Genetic differences between the two strains influence the transcriptional response of key mineral transporter genes and miRNAs under a low-P diet. These divergent host genetic strategies are also associated with distinct gut microbiota profiles, highlighting interactions between host genetics, gene expression, and the microbiome in P utilization.