Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study

Adam G Clooney, Julia Eckenberger, Emilio Laserna-Mendieta, Kathryn A Sexton, Matthew T Bernstein, Kathy Vagianos, Michael Sargent, Feargal J Ryan, Carthage Moran, Donal Sheehan, Roy D Sleator, Laura E Targownik (+3 others)
2020 Gut  
ObjectiveThe 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.DesignHere, 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
more » ... followed longitudinally (at three time points with 16 weeks intervals).ResultsReduced 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.ConclusionThe 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.
doi:10.1136/gutjnl-2020-321106 pmid:32536605 pmcid:PMC7873428 fatcat:trjdw2bpozb7vedhuxh3afrkze