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Background Vitamin D signals through the vitamin D receptor (VDR) which is a member of the nuclear receptor family of transcription factors that play an immunoregulatory role in the gut. Defective signalling due to vitamin D deficiency or decreased mucosal VDR levels has been related to Crohn’s disease (CD). We aim to analyse the acute effects of Vitamin D in the activation of human intestinal fibroblasts. Methods Fibroblasts were isolated from non-damaged and damaged intestinal resection of CD patients and control patients (non-damaged intestine from colon cancer). Fibroblasts were treated with 1,25 Vitamin D3 (10 nM and 100 nM) for 24 h. Gene expression of pro-inflammatory cytokines and COL1A1 was quantified by qPCR and protein levels were determined by western blot. Statistical significance was measured by ANOVA. Results Vitamin D increased the mRNA expression of VDR in fibroblasts obtained from the inflamed and non-inflamed mucosa of CD patients (Figure 1A) and it increased the mRNA of CYP24A1, a VDR target (Figure 1B). Treatment with vitamin D rised in a dose-dependent manner COL1A1 mRNA expression in fibroblasts from CD patients (Figure 1C) and in parallel it induced the expression of pro-inflammatory cytokines (IL1β , IL6) (Figure 1D, 1E). Protein levels of phospho-NFκB and phospho-STAT3 were also higher in fibroblasts treated with Vitamin D from CD patients. Conclusions Our study indicates that an acute treatment of Vitamin D activates an inflammatory pathway and a collagen I expression in human intestinal fibroblasts which may be involved in the initial response in the wound healing. View largeDownload slide View largeDownload slide
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Abstracts of the 13th Congress of ECCO – European Crohn’s and Colitis Organisation S153
1St Vincent's Hopspital, Sydney, Gastroenterology, Sydney, Australia,
2The Australian National University, National Centre for Epidemiology
and Population Health, Canberra, Australia, 3The University of
Western Australia, Centre for Microscopy, Characterisation and
Analysis, Perth, Australia, 4University of Western Australia, School
of Medicine and Pharmacology, Faculty of Health and Medical
Sciences, Perth, Australia, 5St John of God Hospital, Centre for
Inammatory Bowel Diseases, Subiaco, Australia, 6Telethon Kids
Institute, Inammation, Subiaco, Australia, 7The Garvan Institute of
Medical Research, Osteoporosis and Bone Biology, Sydney, Australia,
8St Vincent's Hospital Sydney, Endocrinology, Sydney, Australia
Background: Vitamin D deciency is common among patients with
Crohn’s disease (CD) and has been a proposed risk factor for the devel-
opment and are of CD. It remains unclear, however, if this association
is a result of the inammatory process, or a cause. Furthermore, most
studies have relied on radioimmunoassays to measure 25-hydroxyvita-
min D (25(OH)D), which may be less accurate than the accepted gold
standard of liquid chromatography tandem mass spectrometry (LC/MS/
MS). Circulating 25(OH)D is metabolised to the metabolically active
1,25(OH)2D. The alternative pathway involves the production of the
inactive 24,25(OH)2D via 24-hydroxylase prior to elimination. The
ratio of 25(OH)D:24,25(OH)D may be a more accurate measure of
vitamin D status than 25(OH)D alone. We aimed to characterise vitamin
D metabolism in patients with active and inactive CD using LC/MS/MS.
Methods: We report the baseline cross-sectional results of a prospec-
tive cohort study. Patients were included if they had active CD dened
as ulceration at endoscopy; or a Crohn’s disease Activity Index
(CDAI) >220 and a CRP >10mg/l or faecal calprotectin >250 mg/
kg. Remission was dened as a CDAI <150 and normal inammatory
biomarkers. Patients were excluded if they received corticosteroids
or vitamin D supplementation in the preceding 4 weeks. Serum was
tested for 25(OH)D, epi-25(OH)D, 1,25(OH)D and 24,25(OH)2D
using an LC/MS/MS assay. Validated questionnaires were used to
estimate vitamin D exposure from diet and sunlight. Spearman’s cor-
relation coefcient was used to test correlations and unpaired t-tests
to test differences between active and remission CD groups.
Results: Forty-seven consecutive patients with CD (20 active and 27
remission) were recruited; 55% were male. Median age was 37years
(range 23 to 76yr). Fewer patients in the active group were on immu-
nomodulators (30% vs. 61% p = 0.03) or TNF inhibitors (25% vs.
89% p < 0.001). There was no difference in serum 25(OH)D, epi-
25(OH)D or 1,25(OH)D between the groups. Serum 24,25(OH)2D lev-
els were signicantly lower in the active group (mean 1.3 vs. 2.5ng/ml
p < 0.001) and thus the 25(OH)D:24,25(OH)2D ratio was higher (49.4
vs. 26.1 p < 0.001). There was an inverse correlation between CDAI
and 24,25(OH)2D levels (r2=0.33; p = 0.01). Dietary vitamin D intake
and sunlight exposure were not different between the groups.
Conclusions: In the setting of active inammation, levels of
1,25(OH)2D are maintained by shifting the metabolism of 25(OH)D
to 1,25(OH)2D rather than 24,25(OH)2D, suggesting a reduction in
24-hydroxylase activity to maintain the active metabolite. The ratio
of 25(OH)D:24,25(OH)2D is increased in active disease and may
be a more sensitive marker of vitamin D status in patients with CD.
P121
Characterising and managing issues with food-
related quality of life in inflammatory bowel
disease: a qualitative study of patients and
healthcare professionals
W.  Czuber-Dochan1*, M.Morgan2, M.Lomer1, J.O.Lindsay3,
G.Robert4, K.Whelan1
1King's College London, Faculty of Life Sciences and Medicine,
Department of Nutritional Sciences, London, UK, 2King's College
London, Institute of Pharmacological Sciences, London, UK, 3Bart’s
and the London NHS Trust, Gastroenterology Department, London,
UK, 4King's College London, Faculty of Nursing, Midwifery and
Palliative Care, London, UK
Background: Inammatory bowel disease (IBD) has a profound
impact on diet and nutrition that creates limitations in psychosocial
functioning and impacts quality of life (termed food-related quality
of life, FR-QoL). The issues experienced and the management meth-
ods used by patients with IBD and healthcare professionals (HCPs)
regarding FR-QoL are not well understood.
Methods: Individual semi-structured interviews with 15 IBD patients
reporting issues with FR-QoL; and two focus group interviews with
11 HCPs were audio recorded and transcribed verbatim. Pragmatic
thematic analysis was used to analyse data, with NVivo 11 used for
data management.
Results: Fifteen patients with IBD (10 CD/5 UC) were purposively
selected from UK hospital outpatient clinics (7 females, mean age
34.4 years; range 21–51 years). Individual interviews ranged from
39–70min. Eleven HCPs (3 consultant gastroenterologists, three IBD
registrars, two specialist dietitians, two IBD specialist nurses and one
psychologist) participated in two focus groups over 2h each. Patients
perceived IBD as having a direct impact on their diet, particularly their
food choices and enjoyment of food. This limited their daily life such
as going out, socialising with friends and family, or personal relation-
ships. Several factors, including limited understanding of IBD impact
on body function and food digestion, fear of triggering a are through
eating, anxiety about making the right food choices, were perceived to
contribute to impaired FR-QoL. Patients attempted various methods
to improve FR-QoL including trial and error, food avoidance or exclu-
sion, reducing portion size or frequency of eating; but few approaches
were perceived to have the desired improvement in FR-QoL. Limited
or no dietary advice from HCPs left patients feeling that food-related
issues do not receive the same level of attention as medical manage-
ment. During the focus groups, HCPs identied the factors affecting
patients’ diet and FR-QoL that needed greater attention and they were:
IBD-related (e.g. newly diagnosed, acute inammation, functional
symptoms, strictures and stoma) and non-IBD related (e.g. pregnancy,
allergies, likes/dislikes). HCPs acknowledged FR-QoL advice as a low
priority in a consultation. HCPs recognised insufcient time in clinical
consultations to address more complex issues. Some felt inadequately
prepared to offer diet-specic advice, or assumed that other members
of the multidisciplinary team provide diet-related care and advice.
Conclusions: Both, patients and HCPs emphasised the need for more
individualised care in relation to food and IBD and required quality
and timely sources of information. The development and testing of
interventions designed to address FR-QoL is required.
P122
Vitamin D activates human intestinal fibroblasts
L.Gisbert-Ferrándiz1*, P.Salvador1, D.C.Macias-Ceja2,
J.Cosín-Roger2, D.Ortiz-Masiá3,4, F. Navarro-Vicente5,
S.Calatayud1,4, C.Hernández2, M.D.Barrachina1,4
1University of Valencia, Pharmacology, Valencia, Spain, 2Fisabio
Hospital Dr Peset, Valencia, Spain, 3University of Valencia, Medicine,
Valencia, Spain, 4CIBERehd, Valencia, Spain, 5Hospital of Manises,
Servicio de Cirugía, Valencia, Spain
Background: Vitamin D signals through the vitamin D receptor (VDR)
which is a member of the nuclear receptor family of transcription
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S154 Poster presentations
factors that play an immunoregulatory role in the gut. Defective sig-
nalling due to vitamin D deciency or decreased mucosal VDR levels
has been related to Crohn’s disease (CD). We aim to analyse the acute
effects of Vitamin D in the activation of human intestinal broblasts.
Methods: Fibroblasts were isolated from non-damaged and damaged
intestinal resection of CD patients and control patients (non-dam-
aged intestine from colon cancer). Fibroblasts were treated with 1,25
Vitamin D3 (10nM and 100nM) for 24 h. Gene expression of pro-
inammatory cytokines and COL1A1 was quantied by qPCR and
protein levels were determined by western blot. Statistical signicance
was measured by ANOVA.
Results: Vitamin D increased the mRNA expression of VDR in bro-
blasts obtained from the inamed and non-inamed mucosa of CD
patients (Figure1A) and it increased the mRNA of CYP24A1, a VDR
target (Figure1B). Treatment with vitamin D rised in a dose-dependent
manner COL1A1 mRNA expression in broblasts from CD patients
(Figure1C) and in parallel it induced the expression of pro-inamma-
tory cytokines (IL1β , IL6) (Figure1D, 1E). Protein levels of phospho-
NFκB and phospho-STAT3 were also higher in broblasts treated with
Vitamin D from CD patients.
Conclusions: Our study indicates that an acute treatment of Vitamin
D activates an inammatory pathway and a collagen Iexpression in
human intestinal broblasts which may be involved in the initial
response in the wound healing.
P123
The effect of necrosis inhibition on acute DSS
colitis model of inflammatory bowel disease
D.Lee1,2*, J.S.Koo2, C.H.Kim1, S.H.Hwang1, J.W.Choe2,
S.Y.Kim2, S.W.Jung2, H.J.Yim2, Y.T.Jeen2, S.W.Lee2
1Korea University Ansan Hospital, Internal Medicine, Seoul, South
Korea, 2Korea University College of Medicine, Seoul, South Korea
Background: Inammatory bowel diseases (IBD) were characterised
by uncontrolled chronic inammation, which lead to cell death and
organ damage. In contrast to apoptotic cell death, necrosis is charac-
terised by destruction of cell membrane, which released substances
from the cells causing the inammatory reaction and a cascade of
vicious inammatory cycle resulting in increased necrosis. Although
necrosis is thought be a main cell death mechanism of IBD, few
attempts have been made to reduce necrosis in IBD. Anovel necro-
sis inhibitor (NI, NecroX-7) is recently developed, which blocks the
opening of mitochondrial permeability transition pore and inhibits
necrosis effectively. The aim of this study investigated the effect of
necrosis inhibition in acute murine colitis model and in-vitro study.
Methods: Cleaved PARP-1 fragment band was analysed using west-
ern blot assay in intestinal epithelial cell line (IEC-18, rat) in order
to conrm the necrosis inhibition effect of NI. And acute dextran-
sodium sulfate (DSS) induced colitis was generated in C57BL/6 mice.
NI (30mg/kg) was administered once a day via oral gavage for 8days
from the day before DSS administration. The severity of colitis was
assessed by weight, colon length and histologic score. And HMGB1
immunochemistry was performed on harvested intestine for evalu-
ating necrotic cell death qualitatively. The inammatory cytokines
mRNA expressions were measured by quantitative RT-PCR.
Results: In the necrosis inhibition group, the expression of cleaved
PARP-1 (55kDa, necrosis marker) was reduced compared with the
control group, whereas the cleaved PARP-1 fragment (89kDa, apop-
tosis marker) was not different between groups. In vivo study, NI
treatment signicantly reduced colitis represented by colon length and
histologicscore.
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