Multiomics to elucidate inflammatory bowel disease risk factors and pathways

Abstract

Inflammatory bowel disease (IBD) is an immune-mediated disease of the intestinal tract, with complex pathophysiology involving genetic, environmental, microbiome, immunological and potentially other factors. Epidemiological data have provided important insights into risk factors associated with IBD, but are limited by confounding, biases and data quality, especially when pertaining to risk factors in early life. Multiomics platforms provide granular high-throughput data on numerous variables simultaneously and can be leveraged to characterize molecular pathways and risk factors for chronic diseases, such as IBD. Herein, we describe omics platforms that can advance our understanding of IBD risk factors and pathways, and available omics data on IBD and other relevant diseases. We highlight knowledge gaps and emphasize the importance of birth, at-risk and pre-diagnostic cohorts, and neonatal blood spots in omics analyses in IBD. Finally, we discuss network analysis, a powerful bioinformatics tool to assemble high-throughput data and derive clinical relevance.

Fig. 1 |. Complex pathways lead to IBD.

Complex pathways starting with genetic and non-genetic risk factors and followed by downstream changes lead to inflammatory bowel disease (IBD). Altered signatures prior to disease onset can be ascertained using different omics platforms. These molecular mechanisms reflect the molecular epidemiology paradigm from exposure to disease and include internal dose, biologically effective dose and preclinical effect as intermediate steps. Adapted from images courtesy of ©Mount Sinai Health System.

Fig. 2 |. Differences in the application of early life cohorts and pre-diagnostic cohorts in characterizing various omics signatures of IBD during different periods of life.

While early life cohorts can be used to understand early life events and omics signatures to understand changes in immune function and inflammatory bowel disease (IBD) pathogenesis, pre-diagnostic cohorts can help predict IBD risk and characterize IBD pathogenesis based on signatures closer to IBD diagnosis. Adapted from images courtesy of ©Mount Sinai Health System.

Fig. 3 |. Applications from neonatal screening.

Neonatal blood spots are collected after birth via heel or finger prick, stored on standardized filter paper cards, and can be archived for decades to facilitate screening for congenital metabolic disorders and for future research. Samples from neonatal blood spots can be used to characterize metabolomics, genetics and other omics signatures during the early life period that may be associated with diseases later in life. They represent a paradigm shift in molecular research pertaining to the early life period. Adapted from images courtesy of ©Mount Sinai Health System.