Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases

作者：Jason Lloyd‐Price, Cesar Arze, Ashwin N. Ananthakrishnan, Melanie Schirmer, Julián Ávila-Pacheco, Tiffany Poon, Elizabeth Andrews, Nadim J. Ajami, Kevin S. Bonham, Colin Brislawn, David Casero, Holly Courtney, Antonio González, Thomas G. Graeber, A. Brantley Hall, Kathleen D. Lake, Carol J. Landers, Himel Mallick, Damian R. Plichta, Mahadev Prasad, Ali Rahnavard, Jenny Sauk, Dmitry Shungin, Yoshiki Vázquez‐Baeza, Richard White, IBDMDB Investigators, Jason Bishai, Kevin Bullock, Amy Deik, Courtney Dennis, Jess L. Kaplan, Hamed Khalili, Lauren J. McIver, Christopher J. Moran, Long Nguyen, Kerry A. Pierce, Randall Schwager, Alexandra Sirota-Madi, Betsy W. Stevens, William Tan, Johanna J. ten Hoeve, George Weingart, Robin G. Wilson, Vijay Yajnik, Jonathan Braun, Lee A. Denson, Janet K. Jansson, Rob Knight, Subra Kugathasan, Dermot P. B. McGovern, Joseph F. Petrosino, Thaddeus S. Stappenbeck, Harland S. Winter, Clary B. Clish, Eric A. Franzosa, Hera Vlamakis, Ramnik J. Xavier, Curtis Huttenhower · 发表于：Nature · 年份：2019 · DOI：10.1038/s41586-019-1237-9 · 被引用次数：3316 · 研究领域：Gut microbiota and health、Inflammatory Bowel Disease、Clostridium difficile and Clostridium perfringens research

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease M...