@article{8125ae80abf5487280dc6eb3f6afeb73,
title = "Multi-Omics Analyses Show Disease, Diet, and Transcriptome Interactions With the Virome",
abstract = "Background & Aims: The gut virome includes eukaryotic viruses and bacteriophages that can shape the gut bacterial community and elicit host responses. The virome can be implicated in diseases, such as irritable bowel syndrome (IBS), where gut bacteria play an important role in pathogenesis. We provide a comprehensive and longitudinal characterization of the virome, including DNA and RNA viruses and paired multi-omics data in a cohort of healthy subjects and patients with IBS. Methods: We selected 2 consecutive stool samples per subject from a longitudinal study cohort and performed metagenomic sequencing on DNA and RNA viruses after enriching for viral-like particles. Viral sequence abundance was evaluated over time, as well as in the context of diet, bacterial composition and function, metabolite levels, colonic gene expression, host genetics, and IBS subsets. Results: We found that the gut virome was temporally stable and correlated with the colonic transcriptome. We identified IBS-subset–specific changes in phage populations; Microviridae, Myoviridae, and Podoviridae species were elevated in diarrhea-predominant IBS, and other Microviridae and Myoviridae species were elevated in constipation-predominant IBS compared to healthy controls. We identified correlations between subsets of the virome and bacterial composition (unclassifiable “dark matter” and phages) and diet (eukaryotic viruses). Conclusions: We found that the gut virome is stable over time but varies among subsets of patients with IBS. It can be affected by diet and potentially influences host function via interactions with gut bacteria and/or altering host gene expression.",
keywords = "Bacteria, Bacteriophage, Eukaryotic Viruses, Irritable Bowel Syndrome, Microbiome",
author = "Mihindukulasuriya, {Kathie A.} and Mars, {Ruben A.T.} and Johnson, {Abigail J.} and Tonya Ward and Sambhawa Priya and Lekatz, {Heather R.} and Kalari, {Krishna R.} and Lindsay Droit and Tenghao Zheng and Ran Blekhman and Mauro D'Amato and Gianrico Farrugia and Dan Knights and Handley, {Scott A.} and Kashyap, {Purna C.}",
note = "Funding Information: The authors would like to thank Lyndsay Busby for secretarial assistance and Rosemary Mihindukulasuriya for help with creating figures. This work was supported by National Institutes of Health (NIH) grant DK114007 (Purna C. Kashyap); Center for Individualized Medicine, Mayo Clinic, Rochester, MN (Purna C. Kashyap); Minnesota Partnership for Biotechnology and Medical Genomics (Purna C. Kashyap and Dan Knights); and NIH grant DK116713 (Scott A. Handley). Dan Knights, Scott A. Handley, and Purna C. Kashyap contributed equally to this work. Funding Information: The authors would like to thank Lyndsay Busby for secretarial assistance and Rosemary Mihindukulasuriya for help with creating figures. This work was supported by National Institutes of Health (NIH) grant DK114007 (Purna C. Kashyap); Center for Individualized Medicine, Mayo Clinic, Rochester, MN (Purna C. Kashyap); Minnesota Partnership for Biotechnology and Medical Genomics (Purna C. Kashyap and Dan Knights); and NIH grant DK116713 (Scott A. Handley). Dan Knights, Scott A. Handley, and Purna C. Kashyap contributed equally to this work. Kathie Mihindukulasuriya, PhD (Data curation: Equal; Writing ? original draft: Equal; Writing ? review & editing: Equal). Ruben A. T. Mars, PhD (Data curation: Equal; Writing ? original draft: Equal; Writing ? review & editing: Equal). Abigail Johnson, PhD (Data curation: Equal; Writing ? original draft: Equal; Writing ? review & editing: Equal). Tonya Ward, PhD (Data curation: Supporting; Writing ? review & editing: Supporting). Sambhawa Priya, MSc (Data curation: Supporting; Writing ? review & editing: Supporting). Heather Lekatz, CCRP (Data curation: Supporting). Krishna Kalari, PhD (Data curation: Supporting). Lindsay Droit, MSc (Investigation: Supporting; Methodology: Supporting). Tenghao Zheng, PhD (Data curation: Supporting; Writing ? review & editing: Supporting). Ran Blekhman, PhD (Data curation: Supporting; Writing ? review & editing: Supporting). Mauro D'Amato, PhD (Data curation: Supporting; Writing ? review & editing: Supporting). Gianrico Farrugia, MD (Data curation: Supporting). Dan Knights, PhD (Data curation: Supporting; Resources: Equal; Supervision: Equal; Writing ? review & editing: Supporting). Scott Handley, PhD (Data curation: Supporting; Resources: Equal; Supervision: Equal; Writing ? review & editing: Supporting). Purna Kashyap, MBBS (Data curation: Supporting; Resources: Equal; Supervision: Equal; Writing ? original draft: Equal; Writing ? review & editing: Equal). Conflicts of interest These authors disclose the following: Purna C. Kashyap: Advisory Board of Novome Biotechnologies, ad hoc consultant for Pendulum Therapeutics, IP Group Inc, Otsuka Pharmaceuticals, and Intrinsic Medicine. Purna C. Kashyap holds patent US20170042860A1 for use of tryptamine producing bacteria (?Methods and materials for using Ruminococcus gnavus or Clostridium sporogenes to treat gastrointestinal disorders?), and Purna C. Kashyap 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. Dan Knights 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. The remaining authors disclose no conflicts. Publisher Copyright: {\textcopyright} 2021 AGA Institute",
year = "2021",
month = oct,
doi = "10.1053/j.gastro.2021.06.077",
language = "English",
volume = "161",
pages = "1194--1207.e8",
journal = "Gastroenterology",
issn = "0016-5085",
number = "4",
}