Seasonal changes of circulating 25-hydroxyvitamin D correlate with the lower gut microbiome composition in inflammatory bowel disease patients.

Higher probability of the development of Crohn's disease (CD) and ulcerative colitis (UC) as a possible consequence of the north-south gradient has been recently suggested. Living far north or south of the equator is manifested in fluctuation of vitamin D (vitD) levels depending on the season in both healthy and affected individuals. In the present study we investigate the possible link between the seasonal serum vitD level to the microbial composition of the lower gut of Inflammatory Bowel disease (IBD) patients using 16S rRNA sequencing. Decrease of serum vitD level in winter/spring season in a cohort of 35 UC patients and 39 CD patients was confirmed. Low gut microbiota composition of patients with IBD correlated with the serum level of 25(OH)D that directly coupled to seasonal variability of the sunshine in the central European countries. It is supposed to be related to increased abundance of Actinobacteria and Proteobacteria in UC and Actinobacteria, Fusobacteria, Firmicutes and Bacteroidetes in CD. In summer/autumn period, we observed a reduction in abundance of bacterial genera typical for inflammation like Eggerthella lenta, Fusobacterium spp., Bacteroides spp., Collinsella aerofaciens, Helicobacter spp., Rhodococcus spp., Faecalibacterium prausnitzii; and increased abundance of Pediococcus spp. and Clostridium spp. and of Escherichia/Shigella spp.

Biologic treatment in comparison to methotrexate has positive effect on trabecular bone score in rheumatoid arthritis patients: 1-year follow-up.

INTRODUCTION: Biologic treatment may influence activity of rheumatoid arthritis (RA), as well as areal bone mineral density (aBMD). Decreased aBMD explains the fracture risk in RA patients only partially. The trabecular bone score (TBS), novel texture parameter reflects degradation of trabecular bone and therefore could be used as a further parameter to predict the risk of fragility fracture. OBJECTIVE: To compare the effects of biological disease-modifying antirheumatic drugs (bDMARDs) and conventional synthetic (cs) DMARDs (methotrexate) on aBMD and TBS in patients suffering from active RA. METHODS: A 12 month prospective trial was performed in 105 active RA patients. The cohort was divided into two groups: group 1 (n = 84, mean age 54 yrs) treated with bDMARDs and group 2 (n = 21, mean age 53 yrs) treated with csDMARDs. The mean daily dose of prednisone at baseline was 6.2 and 6.6 mg (NS) between group 1 and 2, respectively. Patients with anti-osteoporotic treatment were not included. All patients received calcium (600 mg) and cholecalciferol (800IU). Lumbar spine (LS) and FN aBMD (by DXA, Hologic) were measured at baseline and after 1 year of treatment. TBS was generated using TBS Insight software (Medimaps, Switzerland). RESULTS: Treatment with bDMARDS led to decrease in mean prednisone dose and to increase of 1.7% (p < 0.05) in TBS and OC levels of 26% (p < 0.001) but not on aBMD and CTX after treatment. The greatest TBS increase (2.7%, p < 0.05) was observed in premenopausal females within group 1. No effect of csDMARDS on measured parameters was observed. CONCLUSION: Treatment of patients suffering from active RA with bDMARDs in comparison to csDMARDS led to increase of TBS, with greater increment of TBS in premenopausal women, despite no change in aBMD.

Decrease of trabecular bone score reflects severity of Crohn's disease: results of a case-control study.

OBJECTIVES: Osteoporosis and osteopaenia are known chronic complications of inflammatory bowel diseases. The trabecular bone score (TBS) provides an indirect measurement of bone microarchitecture, independent of bone mineral density (BMD). PATIENTS AND METHODS: The study was designed as a case-control study with the aim to assess and compare bone quantity and quality in patients with Crohn's disease (CD). We purposefully excluded postmenopausal women and patients on long-term corticosteroid therapy. RESULTS: The cohort consisted of 50 CD patients and 25 healthy controls who matched in age, sex, weight, or vitamin D status. There was no significant difference between CD patients versus controls in the mean lumbar BMD of 0.982±0.119 versus 0.989±0.12 g/cm and the mean TBS score of 1.37±0.12 versus 1.38±0.12. We observed significantly lower TBS, but not lumbar BMD, in CD patients with stricturing (B2, 1.36±0.08) or penetrating (B3, 1.32±0.11) disease compared with those with luminal disease (B1, 1.42±0.11; P=0.003 and <0.0001, respectively). We also observed lower mean±SD TBS in patients on versus not on anti-tumour necrosis factor-α therapy: 1.341±0.138 versus 1.396±0.099, respectively. However, the difference between these groups failed to reach statistical significance (P=0.11). No similar finding was seen comparing lumbar BMD in these groups. CONCLUSION: For the first time, it was observed that TBS, but not BMD, correlates with the severity of CD. Our results therefore suggest that TBS can potentially help to identify high fracture risk CD patients better than BMD alone.

Drug-induced liver injury in inflammatory bowel disease: 1-year prospective observational study.

AIM: To analyze 1-year liver injury burden in inflammatory bowel disease (IBD) patients. METHODS: During a 6-mo inclusion period, consecutive IBD cases having a control visit at IBD center were included. Basic demographics, IBD phenotype and IBD treatment were recorded on entry. Aminotransferase (AT) activities of ALT, AST, ALP and gamma-glutamyl transpeptidase (GGT) were measured at baseline, 3 mo prior to study entry and prospectively every 3 mo for 1 year. Liver injury patterns were predefined as: Grade 1 in ALT 1-3 × upper limit of normal (ULN), grade 2 in ALT > 3 × ULN, hepatocellular injury in ALT > 2 × ULN, cholestatic injury in simultaneous GGT and ALP elevation > ULN. Persisting injury was reported when AT elevations were found on > 1 measurement. Risk factors for the patterns of liver injury were identified among demographic parameters, disease phenotype and IBD treatment in univariate and multivariate analysis. Finally, implications for the change in IBD management were evaluated in cases with persisting hepatocellular or cholestatic injury. RESULTS: Two hundred and fifty-one patients were included having 917 ALT and 895 ALP and GGT measurements. Over one year, grade 1 injury was found in 66 (26.3%), grade 2 in 5 (2%) and hepatocellular injury in 16 patients (6.4%). Persisting hepatocellular injury was found in 4 cases. Cholestasis appeared in 11 cases (4.4%) and persisted throughout the entire study period in 1 case. In multivariate analysis, hepatocellular injury was associated with BMI (OR = 1.13, 1.02-1.26), liver steatosis (OR = 10.61, 2.22-50.7), IBD duration (1.07, 1.00-1.15) and solo infliximab (OR = 4.57, 1.33-15.7). Cholestatic liver injury was associated with prior intestinal resection (OR = 32.7, 3.18-335), higher CRP (OR = 1.04, 1.00-1.08) and solo azathioprine (OR = 10.27, 1.46-72.3). In one case with transient hepatocellular injury azathioprine dose was decreased. In 4 cases with persisting hepatocellular injury, fatty liver or alcohol were most likely causes and IBD treatment was pursued without change. In the case with persisting cholestatic injury, no signs of portal hypertension were identified and treatment with infliximab continued. CONCLUSION: Liver injury was frequent, mostly transient and rarely changed management. Infliximab or azathioprine were confirmed as its risk factors indicating the need for regular AT monitoring.

Vitamin D therapy in inflammatory bowel diseases: who, in what form, and how much?

BACKGROUND: The north­south geographical gradient of inflammatory bowel disease (IBD) prevalence, its epidemiology, the genetic association of vitamin D receptor polymorphisms, and results in animal models suggest that vitamin D plays an important role in the pathogenesis of IBD. AIMS: The purpose of this review was to critically appraise the effectiveness and safety of vitamin D therapy in patients with IBD. METHODS: MEDLINE, Scopus and Google Scholar were searched from inception to May 20, 2014 using the terms 'Crohn's disease', 'ulcerative colitis' and 'vitamin D'. Results: Vitamin D deficiency is common in patients with IBD. Limited clinical data suggest an association between low vitamin D concentration and increased disease activity in both ulcerative colitis (UC) and Crohn's disease (CD). To date, only two small open label trials and one randomized controlled trial have shown a positive effect of vitamin D supplementation on disease activity in patients with CD; no effect has been shown for UC. An optimal vitamin D supplementation protocol for patients with IBD remains undetermined, but targeting serum 25-hydroxy vitamin D [25(OH)D] levels between 30 and 50 ng/mL appears safe and may have benefits for IBD disease activity. Depending on baseline vitamin D serum concentration, ileal involvement in CD, body mass index, and perhaps smoking status, daily vitamin D doses between 1800­10,000 international units/day are probably necessary. CONCLUSION: Increasing preclinical and clinical evidence suggests a role for vitamin D deficiency in the development and severity of IBD. The possible therapeutic role of vitamin D in patients with IBD merits continued investigation.

Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases.

AIM: To investigate the effect of vitamin D (VD) concentrations and VD supplementation on health related quality of life in inflammatory bowel disease (IBD) patients. METHODS: A cohort of 220 IBD patients including 141 Crohn's disease (CD) and 79 ulcerative colitis (UC) patients was followed-up at a tertiary IBD center. A subgroup of the cohort (n = 26) took VD supplements for > 3 mo. Health related quality of life was assessed using the short IBD questionnaire (sIBDQ). VD serum concentration and sIBDQ score were assessed between August and October 2012 (summer/autumn period) and between February and April 2013 (winter/spring period). The mean VD serum concentration and its correlation with disease activity of CD were determined for each season separately. In a subgroup of patients, the effects of VD supplementation on winter VD serum concentration, change in VD serum concentration from summer to winter, and winter sIBDQ score were analyzed. RESULTS: During the summer/autumn and the winter/spring period, 28% and 42% of IBD patients were VD-deficient (< 20 ng/mL), respectively. In the winter/spring period, there was a significant correlation between sIBDQ score and VD serum concentration in UC patients (r = 0.35, P = 0.02), with a trend towards significance in CD patients (r = 0.17, P = 0.06). In the winter/spring period, VD-insufficient patients (< 30 ng/mL) had a significantly lower mean sIBDQ score than VD-sufficient patients; this was true of both UC (48.3 ± 2.3 vs 56.7 ± 3.4, P = 0.04) and CD (55.7 ± 1.25 vs 60.8 ± 2.14, P = 0.04) patients. In all analyzed scenarios (UC/CD, the summer/autumn period and the winter/spring period), health related quality of life was the highest in patients with VD serum concentrations of 50-59 ng/mL. Supplementation with a median of 800 IU/d VD day did not influence VD serum concentration or the sIBDQ score. CONCLUSION: VD serum concentration correlated with health related quality of life in UC and CD patients during the winter/spring period.

Combination therapy with an immunomodulator and anti-TNFα agent improves bone mineral density in IBD patients.

OBJECTIVE: There is a high prevalence of low bone mineral density (BMD) among patients with inflammatory bowel disease (IBD) although there is a lack of clinical data on the impact of IBD specific medications and recommended vitamin D (VD) and calcium (Ca) supplements on it. DESIGN: The cohort consisted of 150 IBD patients. The average change in BMD at the lumbar spine per year (∆BMDL/year) was calculated and the impact of clinical characteristics, medications and VD and Ca supplements was analysed. RESULTS: The prevalence of osteopenia was 69/150 (46%) and osteoporosis was identified in 15/150 (10%) patients at baseline. The presence of osteoporosis was associated with the disease duration OR=1.07 per year of disease duration (95% CI=1.01-1.14), p=0.03. The average ∆BMDL/year was 0.010 g/cm(2)/year. Among patients with no IS the ∆BMDL/year was -0.001±0.010 g/cm(2)/year, with AZA -0.001±0.013 g/cm(2)/year, with anti-TNFα 0.003±0.006 g/cm(2)/year and with COMBO 0.027±0.004 g/cm(2)/year; p<0.05 COMBO vs any other subgroup. ∆BMDL/year among patients treated with CS was -0.031±0.012 g/cm(2)/year versus CS free patients 0.013±0.004 g/cm(2)/year; p<0.001. There was no effect of VD/Ca supplementation on BMDL. CONCLUSIONS: The prevalence of low BMD was 55%. Duration of disease was the only independent predictor of low BMD. The BMDL was reduced by high cumulative dose of CS and improved by combined anti-TNFα/AZA therapy. The supplementation with recommended doses of VD and Ca had no effect on BMDL.

Delayed hypersensitivity reaction after initial dose of infliximab: a case report.

We report here an unusual case of delayed hypersensitivity reaction in a young woman with ulcerative colitis after the first administration of infliximab (IFX). The patient developed severe serum-sickness-like reaction, and her anti-IFX antibody titer increased rapidly after a single infusion of IFX. The possible reason for the delayed hypersensitivity reaction to a single IFX exposure might be the presensitization of the patient by murine antigens as she had been keeping mice and hamsters as pets for several years.

Smoking, breastfeeding, physical inactivity, contact with animals, and size of the family influence the risk of inflammatory bowel disease: A Slovak case-control study.

BACKGROUND: The aetiology of inflammatory bowel disease (IBD) is not known but is likely to involve a combination of genetic predisposition and environmental risk factors. Smoking has been associated consistently with a higher risk of Crohn's disease (CD), while appendectomy and smoking appear to diminish the risk of ulcerative colitis (UC). The roles of other environmental factors are unclear. The aim of the present study was to evaluate the association of CD and UC with several environmental risk factors. METHODS: This case-control study included 338 patients (190 CD, 148 UC) and 355 controls. All subjects completed a detailed questionnaire regarding breastfeeding duration, history of helminthic infections, allergic diseases, appendectomy, household size, housing type, contact with specific domestic animals, physical activity, and smoking. Associations between risk factors and CD and UC were investigated by univariate and multivariate analysis. RESULTS: On multivariate analysis, CD associated with smoking at diagnosis (odds ratio, OR, 3.7, 95% CI 2.2-6.2; p < 0.001), being breastfed for <6 months (OR 2.7, 95% CI 1.7-4.4; p < 0.001), and less than two childhood sporting activities weekly (OR 2.7, 95% CI 1.5-5.0; p < 0.001) and inversely associated with frequent contact with cats in childhood (OR 0.6, 95% CI 0.4-0.9; p < 0.03). UC associated with less than two sporting weekly activities in childhood (OR 2.0, 95% CI 1.1-3.5, p = 0.02), fewer household members in childhood (OR 0.8, 95% CI 0.7-0.98, p = 0.03), and being breastfed for <6 months (OR 1.7, 95% CI 1.02-2.8, p = 0.04). A composite environmental risk index for CD revealed that 47 and 14% of the controls and patients with CD had no risk factors, respectively, and that 14 and 38% of the controls and patients with CD had at least two risk factors, respectively. CONCLUSION: CD and UC associated with infrequent childhood sports activities and short breastfeeding. Furthermore, CD associated with smoking and infrequent contact with animals in childhood. UC associated with a smaller family size in childhood.