Irritable bowel syndrome-like symptoms and health related quality of life two years after Roux-en-Y gastric bypass - a prospective cohort study

Background Irritable bowel syndrome (IBS) is prevalent in patients with morbid obesity. After Roux-en-Y gastric bypass (RYGB) chronic abdominal pain is common, however the etiology is largely unknown. We aimed to study the change in the prevalence of IBS-like symptoms 2 years after RYGB and possible preoperative predictors of such symptoms. Secondly, to evaluate changes in symptoms of constipation and diarrhea, and Health related quality of life (HRQoL). Methods Patients with morbid obesity were included at two obesity centers in South-Eastern Norway. IBS was diagnosed according to the Rome III criteria. Predictors were evaluated in a multivariable logistic regression analysis. Results Of 307 participants operated with RYGB, 233 (76%) completed the study questionnaires. Preoperatively 27/233 participants (12%) had IBS, 2 years after RYGB 61/233 (26%) had IBS-like symptoms (p < 0.001). Eleven participants with IBS preoperatively (41%) did not report such symptoms after RYGB. New onset IBS-like symptoms was identified in 45/206 (22%) after RYGB. Fibromyalgia, low LDL levels, high vitamin B1 levels and IBS before RYGB were independent preoperative predictors of IBS-like symptoms at the follow-up visit. Symptom scores for constipation preoperatively and 2 year after RYGB were 1.5 (0.9) and 1.8 (1.2), and for diarrhea 1.4 (0.9) and 1.8 (1.1), respectively (p < 0.001). We observed a significant improvement in the physical component score for all participants. However, participants with new onset IBS-like symptoms had a significant worsening of the mental component score. Conclusions The prevalence of IBS-like symptoms doubled 2 years after RYGB, and these symptoms were associated with reduced HRQoL. Preoperative IBS and fibromyalgia were strong predictors of postoperative IBS-like symptoms

Acting with the Clock: Clocking Practices in Early Childhood

In this article, the author addresses intra-actions that take place among humans and nonhuman others – the physical world, the materials – in early childhood education’s everyday practices. Her object of study is the clock. Specifically, she provides an example of what it might mean to account for the intra-activity of the material-discursive relations that encompass early childhood education clocking practices. Drawing on the work of Karen Barad and other posthumanist theories, she proposes a particular approach to early childhood clocking practices, an onto-epistemology, as she argues that we learn to act with clocks in early childhood classrooms

Autotaxin activity predicts transplant-free survival in primary sclerosing cholangitis

Autotaxin has been associated with liver disease severity and transplant-free survival. This study aimed to validate autotaxin as a biomarker in two cohorts of Norwegian large-duct PSC patients, one discovery panel (n = 165) and one validation panel (n = 87). Serum activity of autotaxin was measured in diluted sera by a fluorometric enzymatic assay. Patients reaching an end-point, liver transplantation or death, (discovery panel: n = 118 [71.5%]; validation panel: n = 35 [40.2%]), showed higher autotaxin activity compared with the other patients, P < 0.001 and P = 0.004, respectively. Kaplan-Meier survival analyses showed a strong association between increasing autotaxin activity and shorter liver transplant-free survival (discovery panel: P < 0.001, validation panel: P = 0.001). There was no relationship between autotaxin activity and the presence of inflammatory bowel disease or occurrence of hepatobiliary malignancy. In a multivariable analysis, high autotaxin activity was associated with an increased risk of liver transplantation or death (hazard ratio 2.03 (95% confidence interval 1.21–3.40), P < 0.01), independent from Mayo risk score, an in-house enhanced liver fibrosis score and interleukin-8 in serum. In conclusion, increased serum autotaxin activity is associated with reduced liver transplant-free survival independent from Mayo risk score and markers of inflammation and fibrosis

Guanylate cyclase C activation shapes the intestinal microbiota in patients with familial diarrhea and increased susceptibility for Crohn's Disease

Background: With 25% prevalence of Crohn's disease, Familial GUCY2C diarrhea syndrome (FGDS) is a monogenic disorder potentially suited to study initiating factors in inflammatory bowel disease (IBD). We aimed to characterize the impact of an activating GUCY2C mutation on the gut microbiota in patients with FGDS controlling for Crohn's disease status and to determine whether changes share features with those observed in unrelated patients with IBD. Methods: Bacterial DNA from fecal samples collected from patients with FGDS (N = 20), healthy relatives (N = 11), unrelated healthy individuals (N = 263), and IBD controls (N = 46) was subjected to sequencing of the V3-V4 region of the 16S rRNA gene to determine gut microbiota composition. Food frequency questionnaires were obtained from patients with FGDS and their relatives. Results: Compared with healthy controls, FGDS displayed prominent changes in many microbial lineages including increase in Enterobacteriaceae, loss of Bifidobacterium and Faecalibacterium prausnitzii but an unchanged intraindividual (alpha) diversity. The depletion of F. prausnitzii is in line with what is typically observed in Crohn's disease. There was no significant difference in the dietary profile between the patients and related controls. The gut microbiota in related and unrelated healthy controls was also similar, suggesting that diet and familial factors do not explain the gut microbiota alterations in FGDS. Conclusions: The findings support that the activating mutation in GUCY2C creates an intestinal environment with a major influence on the microbiota, which could contribute to the increased susceptibility to IBD in patients with FGDS

Genome-wide association analysis identifies variation in vitamin D receptor and other host factors influencing the gut microbiota

Human gut microbiota is an important determinant for health and disease, and recent studies emphasize the numerous factors shaping its diversity. Here we performed a genome-wide association study (GWAS) of the gut microbiota using two cohorts from northern Germany totaling 1,812 individuals. Comprehensively controlling for diet and non-genetic parameters, we identify genome-wide significant associations for overall microbial variation and individual taxa at multiple genetic loci, including the VDR gene (encoding vitamin D receptor). We observe significant shifts in the microbiota of Vdr−/− mice relative to control mice and correlations between the microbiota and serum measurements of selected bile and fatty acids in humans, including known ligands and downstream metabolites of VDR. Genome-wide significant (P < 5 × 10−8) associations at multiple additional loci identify other important points of host–microbe intersection, notably several disease susceptibility genes and sterol metabolism pathway components. Non-genetic and genetic factors each account for approximately 10% of the variation in gut microbiota, whereby individual effects are relatively small