PT  - JOURNAL ARTICLE
AU  - Adam G Clooney
AU  - Julia Eckenberger
AU  - Emilio Laserna-Mendieta
AU  - Kathryn A Sexton
AU  - Matthew T Bernstein
AU  - Kathy Vagianos
AU  - Michael Sargent
AU  - Feargal J Ryan
AU  - Carthage Moran
AU  - Donal Sheehan
AU  - Roy D Sleator
AU  - Laura E Targownik
AU  - Charles N Bernstein
AU  - Fergus Shanahan
AU  - Marcus J Claesson
TI  - Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study
AID  - 10.1136/gutjnl-2020-321106
DP  - 2021 Mar 01
TA  - Gut
PG  - 499--510
VI  - 70
IP  - 3
4099  - http://gut.bmj.com/content/70/3/499.short
4100  - http://gut.bmj.com/content/70/3/499.full
SO  - Gut2021 Mar 01; 70
AB  - Objective The microbiome contributes to the pathogenesis of inflammatory bowel disease (IBD) but the relative contribution of different lifestyle and environmental factors to the compositional variability of the gut microbiota is unclear.Design Here, we rank the size effect of disease activity, medications, diet and geographic location of the faecal microbiota composition (16S rRNA gene sequencing) in patients with Crohn’s disease (CD; n=303), ulcerative colitis (UC; n = 228) and controls (n=161), followed longitudinally (at three time points with 16 weeks intervals).Results Reduced microbiota diversity but increased variability was confirmed in CD and UC compared with controls. Significant compositional differences between diseases, particularly CD, and controls were evident. Longitudinal analyses revealed reduced temporal microbiota stability in IBD, particularly in patients with changes in disease activity. Machine learning separated disease from controls, and active from inactive disease, when consecutive time points were modelled. Geographic location accounted for most of the microbiota variance, second to the presence or absence of CD, followed by history of surgical resection, alcohol consumption and UC diagnosis, medications and diet with most (90.3%) of the compositional variance stochastic or unexplained.Conclusion The popular concept of precision medicine and rational design of any therapeutic manipulation of the microbiota will have to contend not only with the heterogeneity of the host response, but also with widely differing lifestyles and with much variance still unaccounted for.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Sequence data are available at NCBI SRA PRJNA414072.