Author: Ruben A.T. Mars, Yi Yang, Tonya Ward, Mo Houtti, Sambhawa Priya, Heather R. Lekatz, Xiaojia Tang, Zhifu Sun, Krishna R. Kalari, Tal Korem, Yogesh Bhattarai, Tenghao Zheng, Noam Bar, Gary Frost, Abigail J. Johnson, Will van Treuren, Shuo Han, Tamas Ordog, Madhusudan Grover, Justin Sonnenburg, Mauro D’Amato, Michael Camilleri, Eran Elinav, Eran Segal, Ran Blekhman, Gianrico Farrugia, Jonathan R. Swann, Dan Knights, Purna C. Kashyap
Abstract: The gut microbiome has been implicated in multiple human chronic gastrointestinal(GI) disorders. Determining its mechanistic role in disease has been difficult dueto apparent disconnects between animal and human studies and lack of an integratedmulti-omics view of disease-specific physiological changes. We integrated longitudinalmulti-omics data from the gut microbiome, metabolome, host epigenome, and transcriptomein the context of irritable bowel syndrome (IBS) host physiology. We identified IBSsubtype-specific and symptom-related variation in microbial composition and function.A subset of identified changes in microbial metabolites correspond to host physiologicalmechanisms that are relevant to IBS. By integrating multiple data layers, we identifiedpurine metabolism as a novel host-microbial metabolic pathway in IBS with translationalpotential. Our study highlights the importance of longitudinal sampling and integratingcomplementary multi-omics data to identify functional mechanisms that can serve astherapeutic targets in a comprehensive treatment strategy for chronic GI diseases.