Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome

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 SonnenburgMauro D'Amato, Michael Camilleri, Eran Elinav, Eran Segal, Ran Blekhman, Gianrico Farrugia, Jonathan R. Swann, Dan Knights, Purna C. Kashyap

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view 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. Video Abstract: [Figure presented]. Integrated and longitudinal multiomic analyses of patients with irritable bowel syndrome reveals a role for the gut microbiota in modulating purine metabolism and influencing host gastrointestinal function.

Original languageEnglish (US)
Pages (from-to)1460-1473.e17
JournalCell
Volume182
Issue number6
DOIs
StatePublished - Sep 17 2020

Keywords

  • bile acids
  • diet
  • functional bowel disorders
  • nucleosides
  • physiology
  • secretion
  • short chain fatti acids
  • symptom severity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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