Identification of shared and disease-specific host gene–microbiome associations across human diseases using multi-omic integration
Sambhawa Priya | Postdoctoral Fellow at Broad Institute of MIT and Harvard
While host genetics and gut microbiome have separately been identified as contributing factors to human health and disease, it is unclear how interactions between the two might drive disease risk. The modulation of host gene expression by the gut microbiome has been demonstrated as a potential mechanism by which microbes can affect host physiology. Therefore, understanding the molecular interactions between the microbiome and host gene regulation is critical for unravelling their contribution to the etiology of human diseases. Here, we comprehensively characterize interactions between host gene expression and gut microbiome composition from 416 colonic mucosal samples of patients with colorectal cancer, inflammatory bowel disease, and irritable bowel syndrome. We developed and applied a machine learning-based multi-omic integration framework using Lasso regression and sparse canonical correlation analysis to identify specific and pathway-level interactions between gut microbiome and host transcriptome in each disease. We identified associations between gut microbes and host genes that depict shared as well as disease-specific patterns. We found that a common set of host genes and pathways implicated in gastrointestinal inflammation, gut barrier protection, and energy metabolism are associated with disease-specific gut microbes. Additionally, we also found that mucosal gut microbes that have been implicated in all three diseases, such as Streptococcus, are associated with different host pathways in each disease, suggesting that similar microbes can affect host pathophysiology in a disease-specific manner through regulation of different host genes. Overall, our findings suggest that a complex crosstalk between the gut microbes and host gene regulation potentially contributes to the underlying pathophysiology of gastrointestinal diseases.
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