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Dynamics of the human gut microbiome in inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The aetiology of IBD is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behaviour of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease 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 will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.

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Figure 1: Defining a healthy plane.
Figure 2: The gut microbiomes of different IBD subtypes display different distributions relative to a healthy plane.
Figure 3: Correlation between faecal calprotectin concentrations and distance to a defined HP in three-dimensional ordination space.
Figure 4: Microbiome dynamics of selected individuals from each IBD subtype and a healthy control.

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Acknowledgements

This research was partially supported by the United States National Institutes of Health (grant NIH IU54DE023798-01), the Pacific Northwest National Laboratory (contract DE-AC05-76RLO1830) and by the Crohn's and Colitis Foundation of America. Financial support was also provided by the Örebro University Hospital Research Foundation (grant OLL-507001), the Swedish Foundation For Strategic Research (grant RB13-0160) and the Swedish Research Council (521-2011-2764). Additional support was provided by a grant to Juniata College from the Howard Hughes Medical Institute through the Precollege and Undergraduate Science Education Program and the National Science Foundation (NSF award no. DBI-1248096). R.K. was a Howard Hughes Institute Early Career Scientist for part of the duration of this project.

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Authors

Contributions

J.H. and J.K.J. designed the study. J.H. carried out the clinical study and collected samples and clinical data. C.J.B., Y.V.-B., W.A.W., D.M., M.D'A., F.B., A.G., R.L., E.E.M., L.M.B. and M.F.D. performed bioinformatics and statistical analyses of the data. C.J.B., Y.V.-B., W.A.W. and A.G. produced the figures. J.H., C.J.B., Y.V.-B., J.K.J. and R.K. wrote the majority of the text with input from all co-authors.

Corresponding author

Correspondence to Janet K. Jansson.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Legend for Supplementary Video 1, Legend for Supplementary Dataset 1, Supplementary Tables 1–4 and Supplementary Figures 1–4. (PDF 698 kb)

Supplementary Dataset 1

Clinical metadata for patients and samples. (TXT 287 kb)

Supplementary Video 1

Dynamics of healthy controls and IBD subtypes within ordinated UniFrac space. (MOV 72737 kb)

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Halfvarson, J., Brislawn, C., Lamendella, R. et al. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat Microbiol 2, 17004 (2017). https://doi.org/10.1038/nmicrobiol.2017.4

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