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.
Bibliographical noteFunding Information:
The authors would like to thank Lyndsay Busby for secretarial assistance and J.M. Nielsen for help with figures. This work was supported by NIH grant DK114007 (P.C.K.); the Center for Individualized Medicine, Mayo Clinic , Rochester, MN (P.C.K.); the Minnesota Partnership for Biotechnology and Medical Genomics (P.C.K. and D.K.); the STRATiGRAD PhD training program of Imperial College London ( https://www.imperial.ac.uk/stratigrad/ ) (Y.Y.); Société des Produits Nestle (J.R.S.); Imperial College NIHR BRC (J.R.S.); and NIH grant R35-GM128716 (R.B.).
The authors would like to thank Lyndsay Busby for secretarial assistance and J.M. Nielsen for help with figures. This work was supported by NIH grant DK114007 (P.C.K.); the Center for Individualized Medicine, Mayo Clinic, Rochester, MN (P.C.K.); the Minnesota Partnership for Biotechnology and Medical Genomics (P.C.K. and D.K.); the STRATiGRAD PhD training program of Imperial College London (https://www.imperial.ac.uk/stratigrad/) (Y.Y.); Soci?t? des Produits Nestle (J.R.S.); Imperial College NIHR BRC (J.R.S.); and NIH grant R35-GM128716 (R.B.). D.K and P.C.K. designed the experiments and the overall data analysis. R.A.T.M. D.K. and P.C.K. wrote the manuscript with input from co-authors. H.R.L. Y.B. and P.C.K. coordinated human subject recruiting and sampling. Y.Y. T.W. and H.R.L. contributed to sample processing data generation and analysis. T.W. X.T. Z.S. T.Z. W.v.T. S.H. Y.Y. and R.A.T.M. analyzed data. S.P. X.T. K.R.K. T.K. M.H. N.B. W.v.T. S.H. R.B. Y.Y. and R.A.T.M. performed data integration. T.O. M.G. M.D. M.C. E.E. E.S. R.B. G. Farrugia, G. Frost, J.S. J.R.S. D.K. K.R.K. and P.C.K directed research and provided critical feedback. T.O. M.G. G. Farrugia, M.C. and P.C.K. performed clinical data analysis. Y.B. and P.C.K. contributed to design and execution of Ussing chamber experiments. P.C.K. is on the Advisory Board of Novome Biotechnologies and is an ad hoc consultant for Pendulum Therapeutics, IP group, and Otsuka Pharmaceuticals. P.C.K. holds patent US20170042860A1 for use of tryptamine producing bacteria (?Methods and materials for using Ruminococcus gnavus or Clostridium sporogenes to treat gastrointestinal disorders?), and P.C.K. and Mayo Clinic have a financial interest related to this research. These interests have been reviewed and managed in accordance with Mayo Clinic Conflict-of-Interest policies. D.B.K. serves as CEO of CoreBiome, a company involved in the commercialization of microbiome analysis and a wholly owned subsidiary of OraSure Technologies. These interests have been reviewed and managed by the University of Minnesota in accordance with its Conflict-of-Interest policies.
© 2020 Elsevier Inc.
- bile acids
- functional bowel disorders
- short chain fatti acids
- symptom severity
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't