‘Epigenetics, molecular pathways, and data integration to derive biological networks related to myo-inositol and P utilization in two contrasting high-yielding laying hen strains’

Contact: Dr. Siriluck Wimmers

Duration: 2022-2025

Funding: Deutsche Forschungsgemeinschaft, DFG WI 3719/8-2 / AOBJ: 680776

In the initial funding period, we identified miRNAs as regulatory molecules mediating host-microbiome interactions in Japanese quails phenotypically divergent for phosphorus utilization (PU). The integration of phenotypic data with transcriptome and microbiome data revealed genetically regulated mRNA and miRNA transcripts and microbes associated with PU. Focussing on two high-yielding and genetically different laying hen lines, miRNA- and target transcript profiles were analysed at the background of variable dietary mineral supply and at different production periods. Many miRNAs and their target transcripts changed across production periods, with the most prominent changes occurring at 16–24 weeks of age. Differentially expressed miRNAs and their targets between strains mediated the regulation of molecular pathways of energy metabolism and mitochondrial functions in the one laying hen strain, whereas in the other strain modulation of immune and inflammatory pathways was evident. Our ongoing integration of omics data, including transcripts, microbiota, metabolites, immune and other physiological phenotypes, revealed key molecular drivers of P homeostasis along the lifespan and differentiated between strains. The identified functional, regulatory pathways and molecular signatures related to inositol-phosphate, myo-inositol and P metabolism as well as specific molecular markers are used in the renewal period. In addition, we observed differences in gene activity that were not only genetically based (by strain), but also evident at the epigenetic level, where significant changes occurred in transcripts of key DNA-methylation and histone deacetylation enzymes. Therefore, we will investigate additional epigenetic modifications to gain further insights into host-gut microbiota interactions at different production periods and in the two strains using samples of the first funding period and new samples of the renewal period. Narrowing the window of the transition period from pullet to laying hen of different strains of laying hens will provide deeper molecular insights into the inositol phosphate metabolic system at this critical phase. In addition, complete removal of mineral P from the feed and MI-supplements may promote changes not only at physiological but also at molecular levels. Single-cell transcript levels, which provide a clearer picture for identifying intestinal cell types of heterogeneous intestinal tissues, reflect the specific cellular activity affecting P utilization and metabolism between strains of laying hens. Finally, integration of data from different omics levels, metabolic and physiological measurements obtained in the research unit with up-to-date approaches such as supervised and unsupervised machine learning will be performed to complement the steps of multi-OMICs integration and further characterize the associations between metabolic phenotype, genetic variation, epigenetic mechanisms, nutrient uptake and host gut microbiota.