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Title: Dynamics of the human gut microbiome in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is characterized by flares of inflammation with periodic need for increased medication and sometimes even surgery. IBD etiology is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD diseases, including ulcerative colitis (UC), colonic Crohn’s Disease (CCD), and ileal CD (ICD). Although IBD is dynamic, microbiome studies have primarily focused on single timepoints or few individuals. Here we dissect the long-term dynamic behavior of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than healthy individuals, based on deviation from a newly-defined healthy plane (HP). ICD subjects deviated most from the HP, especially subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between observed dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results help guide therapies that will re-direct the gut microbiome towards a healthy state and maintain remission in IBD.

Authors:
ORCiD logo; ; ; ; ; ; ; ; ; ; ; ; ORCiD logo;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1356478
Report Number(s):
PNNL-SA-122629
Journal ID: ISSN 2058-5276; 453060036
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature Microbiology; Journal Volume: 2
Country of Publication:
United States
Language:
English
Subject:
gut, human; inflammatory Bowel

Citation Formats

Halfvarson, Jonas, Brislawn, Colin J., Lamendella, Regina, Vázquez-Baeza, Yoshiki, Walters, William A., Bramer, Lisa M., D'Amato, Mauro, Bonfiglio, Ferdinando, McDonald, Daniel, Gonzalez, Antonio, McClure, Erin E., Dunklebarger, Mitchell F., Knight, Rob, and Jansson, Janet K.. Dynamics of the human gut microbiome in inflammatory bowel disease. United States: N. p., 2017. Web. doi:10.1038/nmicrobiol.2017.4.
Halfvarson, Jonas, Brislawn, Colin J., Lamendella, Regina, Vázquez-Baeza, Yoshiki, Walters, William A., Bramer, Lisa M., D'Amato, Mauro, Bonfiglio, Ferdinando, McDonald, Daniel, Gonzalez, Antonio, McClure, Erin E., Dunklebarger, Mitchell F., Knight, Rob, & Jansson, Janet K.. Dynamics of the human gut microbiome in inflammatory bowel disease. United States. doi:10.1038/nmicrobiol.2017.4.
Halfvarson, Jonas, Brislawn, Colin J., Lamendella, Regina, Vázquez-Baeza, Yoshiki, Walters, William A., Bramer, Lisa M., D'Amato, Mauro, Bonfiglio, Ferdinando, McDonald, Daniel, Gonzalez, Antonio, McClure, Erin E., Dunklebarger, Mitchell F., Knight, Rob, and Jansson, Janet K.. Mon . "Dynamics of the human gut microbiome in inflammatory bowel disease". United States. doi:10.1038/nmicrobiol.2017.4.
@article{osti_1356478,
title = {Dynamics of the human gut microbiome in inflammatory bowel disease},
author = {Halfvarson, Jonas and Brislawn, Colin J. and Lamendella, Regina and Vázquez-Baeza, Yoshiki and Walters, William A. and Bramer, Lisa M. and D'Amato, Mauro and Bonfiglio, Ferdinando and McDonald, Daniel and Gonzalez, Antonio and McClure, Erin E. and Dunklebarger, Mitchell F. and Knight, Rob and Jansson, Janet K.},
abstractNote = {Inflammatory bowel disease (IBD) is characterized by flares of inflammation with periodic need for increased medication and sometimes even surgery. IBD etiology is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD diseases, including ulcerative colitis (UC), colonic Crohn’s Disease (CCD), and ileal CD (ICD). Although IBD is dynamic, microbiome studies have primarily focused on single timepoints or few individuals. Here we dissect the long-term dynamic behavior of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than healthy individuals, based on deviation from a newly-defined healthy plane (HP). ICD subjects deviated most from the HP, especially subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between observed dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results help guide therapies that will re-direct the gut microbiome towards a healthy state and maintain remission in IBD.},
doi = {10.1038/nmicrobiol.2017.4},
journal = {Nature Microbiology},
number = ,
volume = 2,
place = {United States},
year = {Mon Feb 13 00:00:00 EST 2017},
month = {Mon Feb 13 00:00:00 EST 2017}
}
  • Introduction—Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. Here we sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Methods—Adult male C57Bl/6 mice, germ-free (GF), Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for four weeks. Fecal samples were collected for gut microbiota analysis via 16S rRNA T-RFLP and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. GF mice were conventionalized withmore » gut microbes from treated- and non-treated groups to determine their functional capacities in recipient hosts. Results—Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period. Furthermore, a significant down-regulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a pro-inflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout (IL10-KO) mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pre-treated with DEX, however, ameliorated symptoms of inflammation. We conclude that commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC exposure. These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.« less
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