@article{c6bc7096704549e1bb683fe330d4f0c8,
title = "Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome",
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 subtyp-especific 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.",
author = "Mars, {Ruben A. T.} and Tonya Ward and Mo Houtti and Sambhawa Priya and Lekatz, {Heather R.} and Xiaojia Tang and Zhifu Sun and Kalari, {Krishna R.} and Yogesh Bhattarai and Tenghao Zheng and Noam Bar and Gary Frost and Johnson, {Abigail J.} and {van Treuren}, Will and Shuo Han and Tamas Ordog and Madhusudan Grover and Justin Sonnenburg and Mauro D'Amato and Michael Camilleri and Eran Elinav and Eran Segal and Ran Blekhman and Gianrico Farrugia and Swann, {Jonathan R.} and Dan Knights and Kashyap, {Purna C.}",
note = "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{\'e}t{\'e} des Produits Nestle (J.R.S.); Imperial College NIHR BRC (J.R.S.); and NIH grant R35-GM128716 (R.B.). Author contributions - 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.",
year = "2020",
month = sep,
day = "17",
doi = "10.1016/j.cell.2020.08.007",
language = "الإنجليزيّة",
volume = "182",
pages = "1460--1473",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "6",
}