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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 (n=161), 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.

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Objective. To describe the sources of stress for persons with IBD and changes with changes in symptoms. Methods. 487 participants were recruited from a population-based IBD registry. Stress was measured at study entry and three months later, using a general stress measure and the Sources of Stress Scale. Four symptom pattern groups were identified: persistently inactive, persistently active, inactive to active, and active to inactive. Results. General stress levels were stable within each symptom pattern group over the three-month period, even for those with changing symptom activity. The persistently active group had higher general stress at month 0 and month 3 than the persistently inactive group and higher mean ratings of most sources of stress. IBD was rated as a highly frequent source of stress by 20–30% of the persistently active group compared to 1-2% of the inactive group. Finances, work, and family were rated as high frequency stresses in the persistently active group at a similar level to IBD stress. In the groups with fluctuating symptoms, there was little change in stress ratings with changes in symptom activity. Conclusion. Stress was experienced across several domains in addition to stress related to IBD. Persons with active symptoms may benefit from targeted stress interventions.