Longitudinal multi-omics reveals subset-specific mechanisms underlying irritable bowel syndrome

The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders but it has been difficult to determine its mechanistic role in disease pathogenesis due to the apparent disconnect between animal and human studies and a lack of integrated multi-omics approach in relation to disease specific physiologic changes. To uncover such mechanisms, we integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related changes in microbial composition and functions. A subset of these changes corresponds to host physiological changes in IBS. Using integration of multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with potential effects on gastrointestinal barrier function. This study highlights the importance of integrating longitudinal complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases.