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

The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease pathogenesis has been difficult due to the apparent disconnect between animal and human studies and a lack of an integrated multi-omics view in the context of disease-specific physiological changes. 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 variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. We performed a longitudinal multi-omics study in humans, in an attempt to elucidate mechanistic roles for the gut microbiome in the pathophysiology of IBS. Healthy subjects and IBS-C and IBS-D patients between 18-65 years old who expressed interest were invited to undergo screening to assess eligibility. Participants were given the option of undergoing two flexible sigmoidoscopies. All IBS-C and IBS-D subjects fulfilled Rome III criteria. Recruitment of healthy subjects was matched with IBS subjects for age, sex and BMI.