Deciphering the Coordinated Roles of Host Genome, Duodenal Mucosal Genes, and Microbiota in Regulating Complex Traits in Chicken

Abstract

Abstract The complex interactions between host genetics and the gut microbiome are well recognized; however, the specific impact of gene expression pattern and microbial composition on each other remains to be further explored. Here we investigated this complex interplay within a sizable population of 705 hens, employing integrative analyses to examine the relationships among host genetics, mucosal gene expression, and the gut microbiota. Specific microbial taxa exhibited a strong adherence to the host genomic variants, particularly in the cecum such as the Christensenellaceae family with a heritability (h2) of 0.365. We proposed a novel concept regulatability (\({r}_{b}^{2}\)), which was derived from h2, to quantify the cumulative effects of gene expression on the given phenotypes. The duodenal mucosal transcriptome emerged as a potent influencer of duodenal microbial taxa, with exceptionally higher \({r}_{b}^{2}\) values (0.17 ± 0.01, mean ± SE) compared to h2 (0.02 ± 0.00). Through a comparative analysis of chickens and humans, we revealed similar average microbiability (m2) values of 0.18 and 0.20, and significant distinctions in average \({r}_{b}^{2}\) values (0.17 vs 0.04). Notably, cis heritability (\({h}_{cis}^{2}\)) quantifies the impact of genetic variations proximal to a gene on its expression, while trans heritability (\({h}_{trans}^{2}\)) assesses the influence of distant genetic variations. Higher \({h}_{trans}^{2}\) values compared to \({h}_{cis}^{2}\), and a greater prevalence of trans-regulated genes over cis-regulated ones underscored the significant role of loci outside the cis-window in shaping gene expression levels. Furthermore, our exploration into the regulation of duodenal mucosal genes and microbiota on 18 complex traits enhanced our understanding of their regulatory mechanism, in which gene CHST14 and its regulatory relationships with Lactobacillus salivarius jointly facilitated the deposition of abdominal fat. This study has enhanced our understanding of host-microbe dynamics, which helps to devise strategies to modulate host-microbe interactions for improving economic traits in chicken.