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

Cell. 2020 Sep 17;182(6):1460-1473.e17. doi: 10.1016/j.cell.2020.08.007. Epub 2020 Sep 10.


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.

Keywords: bile acids; diet; functional bowel disorders; nucleosides; physiology; secretion; short chain fatti acids; symptom severity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • Biopsy
  • Butyrates / metabolism
  • Chromatography, Liquid
  • Cross-Sectional Studies
  • Epigenomics
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / genetics*
  • Gastrointestinal Microbiome / physiology
  • Gene Expression Regulation / genetics*
  • Gene Expression Regulation / physiology
  • Host Microbial Interactions / genetics
  • Humans
  • Hypoxanthine / metabolism
  • Irritable Bowel Syndrome / genetics
  • Irritable Bowel Syndrome / metabolism*
  • Irritable Bowel Syndrome / microbiology
  • Longitudinal Studies
  • Male
  • Metabolome* / physiology
  • Mice
  • Observational Studies as Topic
  • Prospective Studies
  • Purines / metabolism*
  • Software
  • Tandem Mass Spectrometry
  • Transcriptome / genetics*
  • Transcriptome / physiology


  • Bile Acids and Salts
  • Butyrates
  • Purines
  • Hypoxanthine