ObjectivePatients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case–control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD.DesignStool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2, CARD9, ATG16L1, IRGM and FUT2.ResultsStrikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10−13).ConclusionsWe show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD.

The prevalence of GI complaints during and after running was low compared with that reported in other studies, which is partly due to the definition of "symptomatic" used in our study. The risk factors associated with becoming symptomatic were identical to those in other studies. The relationship between complaints during the run and the type of complaints afterwards suggests a role of GI ischaemia in the pathophysiology of running-induced GI symptoms.

Summary Background The prevalence of exercise‐induced gastrointestinal (GI) symptoms has been reported up to 70%. The pathophysiology largely remains unknown. Aim To review the physiological and pathophysiological changes of the GI‐tract during physical exercise and the management of the most common gastrointestinal symptoms. Methods Search of the literature published in the English and Dutch languages using the Pubmed database to review the literature that focused on the relation between splanchnic blood flow (SBF), development of ischaemia, postischaemic endotoxinemia and motility. Results During physical exercise, the increased activity of the sympathetic nervous system (SNS) redistributes blood flow from the splanchnic organs to the working muscles. With prolonged duration and/or intensity, the SBF may be decreased by 80% or more. Most studies point in the direction of increased SNS‐activity as central driving force for reduction in SBF. A severely reduced SBF may frequently cause GI ischaemia. GI‐ischaemia combined with reduced vagal activity probably triggers changes in GI‐motility and GI absorption derangements. GI‐symptoms during physical exercise may be prevented by lowering the exercise intensity, preventing dehydration and avoiding the ingestion of hypertonic fluids. Conclusions Literature on the pathophysiology of exercise‐induced GI‐symptoms is scarce. Increased sympathetic nervous system activity and decreased splanchnic blood flow during physical exercise seems to be the key factor in the pathogenesis of exercise‐induced GI‐symptoms, and this should be the target for symptom reduction.

Introduction: Blood C-reactive protein (CRP) and fecal calprotectin levels are routinely measured as surrogate markers of disease activity in Inflammatory Bowel Disease (IBD), but often do not correlate well with the degree of mucosal inflammation in the intestine as established by endoscopy. Therefore, novel predictive biomarkers are urgently needed that better reflect mucosal disease activity in IBD. The aim of this study was to identify a combination of serum inflammatory biomarkers predictive for endoscopic disease activity.Methods: Serum concentrations of 10 inflammatory biomarkers were analyzed in 118 IBD patients [64 Crohn's disease (CD), 54 ulcerative colitis (UC)] and 20 healthy controls. In a subset of 71 IBD patients, endoscopic disease activity was established. Non-parametric ROC estimation with bootstrap inference was used to establish the best combination of inflammatory biomarkers predicting endoscopic disease activity.Results: Six (6) inflammatory biomarkers (serum amyloid A (SAA), Eotaxin-1, IL-6, IL-8, IL-17A, and TNF-α) showed better prediction of IBD disease activity than routine measures (CRP, fecal calprotectin and HBI/SCCAI scores). The best combination of predictive inflammatory biomarkers consisted of serum SAA, IL-6, IL-8, and Eotaxin-1, showing an optimism-adjusted area under the ROC (AuROC) curve of 0.84 (95% CI: 0.73–0.94, P < 0.0001), which predicted significantly better (P = 0.002) than serum CRP levels with an AuROC of 0.57 (95% CI: 0.43–0.72, P = 0.32).Conclusion: The combination of SAA, IL-6, IL-8, and Eotaxin-1 reliably predicts endoscopic disease activity in IBD and might be valuable for monitoring disease activity and management of the disease.