Systems Biology Approaches to Unravel Gut-Immune-Bone Pathways Altered by Estrogen Loss and Dietary Intervention

Aging in women is associated with estrogen loss, an inflammatory process that affects tissues throughout the body. This inflammation has widespread effects on women's health, increasing their risk of postmenopausal osteoporosis, stroke, and heart disease. Prebiotic dietary fibers are a promising treatment modality to reduce gut, bone, and systemic inflammation. However, there is a gap in our mechanistic understanding of how estrogen and prebiotic fibers affect these tissues separately and in combination. Computational models, paired with targeted experiments, can accelerate the discovery process by providing mechanistic insights to guide experimental design. To this end, we are using systems biology methods to explore heterogeneous data from the bone, serum, and gut tissue during estrogen loss and dietary intervention experiments. Gut measurements include bulk RNA sequence results. We are using deconvolution to infer cell composition and provide insight into cell-type-specific signals. These results will enable systems-level analysis of tissue, cellular, and genetic responses that we will use to inform and constrain mechanistic models of estrogen inflammation and fiber-based treatments. Finally, we are exploring data-driven models that can leverage our multi-modal -omics, molecular, and phenotypic data to provide additional insights.