Deficiency In Inflammatory Bowel Disease Research Articles

Micronutrient deficiencies in inflammatory bowel disease: an incidence analysis.

Micronutrient deficiencies associated with malnutrition in patients with inflammatory bowel disease (IBD) can lead to complications including anemia, coagulopathy, poor wound healing, and colorectal cancer. This study aimed to investigate micronutrient deficiencies (copper, vitamins A, B 9 , E, and K) in IBD patients and highlight associated symptoms to aid in the recognition of micronutrient deficiencies. A retrospective electronic chart review was performed on adults diagnosed with Crohn's disease or ulcerative colitis hospitalized at a tertiary care center for IBD flare between January 2013 and June 2017. Patients with serum or whole blood micronutrient levels were included. Pregnant and incarcerated patients were excluded. A total of 611 IBD patients (440 Crohn's disease, 171 ulcerative colitis) met the inclusion criteria. Micronutrients were assessed in a subset of IBD patients (copper: 12.3%, A: 10.1%, B 9 : 95.9%, E: 10.3%, and K: 4.6%). Overall, 10.1% of patients had micronutrient deficiencies. The proportion of patients with copper, A, B 9 , E, and K deficiencies were 25.4, 53.3, 1.9, 23.7, and 29.4% for Crohn's disease and 50, 52.9, 1.2, 43.8, and 18.2% for ulcerative colitis, respectively. The most common symptoms or historical features associated with micronutrient deficiency were anemia (copper, B 9 ), muscle weakness (copper, E) thrombocytopenia, fatigue (copper, B 9 ), diarrhea (B 9 ), dry skin, hyperkeratosis, pruritus, significant weight loss, elevated C-reactive protein (A), bleeding, and osteoporosis (K). Micronutrient deficiencies are common in IBD patients, yet they are not routinely assessed. Copper, vitamins A, E, and K deficiencies are particularly underrecognized. Associated historical features should raise suspicion and prompt assessment and treatment.

Calcium deficiency is associated with malnutrition risk in patients with inflammatory bowel disease

ABSTRACT Background and Aim Patients with inflammatory bowel disease (IBD) often have the condition of malnutrition, which can be presented as sarcopenia, micronutrient deficiencies, etc. Trace elements (magnesium, calcium, iron, copper, zinc, plumbum and manganese) belonging to micronutrients, are greatly vital for the assessment of nutritional status in humans. Trace element deficiencies are also the main manifestation of malnutrition. Calcium (Ca) has been proved to play an important part in maintaining body homeostasis and regulating cellular function. However, there are still a lack of studies on the association between malnutrition and Ca deficiency in IBD. This research aimed to investigate the role of Ca for malnutrition in IBD patients. Methods We prospectively collected blood samples from 149 patients and utilized inductively coupled plasma mass spectrometry to examine their venous serum trace element concentrations. Logistic regression analyses were used to investigate the association between Ca and malnutrition. Receiver operating characteristic (ROC) curves were generated to calculate the cutoffs for determination of Ca deficiency. Results Except Ca, the concentrations of the other six trace elements presented no statistical significance between non-malnutrition and malnutrition group. In comparison with the non-malnutrition group, the serum concentration of Ca decreased in the malnutrition group (89.36 vs 87.03 mg/L, p = 0.023). With regard to ROC curve, Ca < 87.21 mg/L showed the best discriminative capability with an area of 0.624 (95% CI: 0.520, 0.727, p = 0.023). Multivariate analyses demonstrated that Ca < 87.21 mg/L (OR = 3.393, 95% CI: 1.524, 7.554, p = 0.003) and age (OR = 0.958, 95% CI: 0.926, 0.990, p = 0.011) were associated with malnutrition risk. Serum Ca levels were significantly lower in the malnutrition group than those in the non-malnutrition group among UC patients, those with severe disease state or the female group. Conclusions In patients with IBD, Ca deficiency is an independent factor for high malnutrition risk.

A-041 Measurement of Plasma 3-Hydroxyisovalerylcarnitine by LC-MS/MS to Predict Marginal Biotin Deficiency in Inflammatory Bowel Disease

Abstract Background Biotin’s role in the immune response have emergently revealed that biotin is related to inflammation and that its deficiency leads to an increase in the level of proinflammatory cytokines. A biotin-deficient diet was recently shown to induce a colitis-like phenotype in mice, alleviated by biotin substitution. Mice with dextran sulphate sodium (DSS)-induced colitis showed biotin deficiency and significantly reduced biotin absorption. Oral biotin substitution reversed DSS colitis and induced remission. Diagnosis of biotin deficiency is rather challenging since based solely on measurement of circulating biotin levels has been shown to be insufficiently sensitive for clinical purposes. Increased urinary excretion of biotin metabolites, is suggested as a sensitive indicator of biotin deficiency. However, 24 h urine collection is time consuming, expensive, and the test relies on correct collection of samples by the patient, thus if this is not done properly the results may be inaccurate. 3HIVc increases in the case of biotin deficiency as a response to the decreased activity of biotin dependent enzyme methyl crotonyl-coenzyme. Analysis of circulating 3HIVc levels by LC-MS/MS has been found to be one of the most sensitive markers of biotin depletion. Methods Study cohort conducted with 100 inflammatory bowel disease (IBD) patients (20–60 years, 40 females) whom diagnosed according to standard clinical, radiological and pathological criteria and 100 healthy controls (20–60 years, 40 females). Of the patients 58/100 had Crohn’s Disease (CD), 42/100 had ulcerative colitis (UC) and 29/100 were in inflammatory state (serum high sensitivity C reactive protein (hsCRP) concentrations &amp;gt;5 mg/L). Standard serum and citrate-plasma samples were withdrawn between 8:00–10:00 h in the clinic after overnight fasting and stored at −20 °C until the analysis. Complete blood count (CBC), high sensitivity C reactive protein (hsCRP), fecal calprotectin (fCal) were determined with standard methods in serum matrix. 3-Hydroxyisovalerylcarntine (3HIVc) levels were determined by a commerical LC-MS/MS Kit in citrate plasma (KM3200, Immundiagnostik AG, Germany). Results Patients with IBD were found to have significantly higher 3HIVc levels than controls (6.1 ± 2.4 ng/mL vs 5.1 ± 2.1 ng/mL respectively, P = 0.004). 3HIVc concentrations were compared according to different disease characteristics within the patient group: circulating 3HIVc levels were found to be similar in patients with CD and UC (5.2 ± 2.1 ng/mL vs 4.9 ± 2.1, P = 0.451). Patients were also found to have similar circulating 3HIVc concentrations irrespective of whether or not inflammatory activity was present (5.1 ± 2.0 ng/mL in inflammatory vs 5.7 ± 2.4 ng/mL in noninflammatory conditions, P = 0.131). Conclusion The clinical findings of this study are in line with the existing preclinical evidence indicating that biotin deficiency is more common in patients with IBD in comparison to healthy controls in a clinical setting. However, surprisingly, the biotin status of patients with IBD was not found to differ according to inflammatory status. Therefore, there is still a room for more comprehensive look into the relationship between IBD related inflammation and biotin deficiency. Moreover, LC-MS/MS analysis of plasma 3HIVc has the potential to help clinicians to define biotin repletion and help to clearify the latter relation.

Micronutrients and Their Role in Inflammatory Bowel Disease: Function, Assessment, Supplementation, and Impact on Clinical Outcomes Including Muscle Health.

The incidence of inflammatory bowel disease (IBD) continues to rise worldwide, and patients with IBD are at increased risk for malnutrition and micronutrient deficiencies. The etiology of malnutrition and micronutrient deficiencies in IBD is multifactorial and includes reduced oral intake, increased intestinal loss, malabsorption, increased nutritional needs in the setting of a hyper catabolic state, medication effects, and altered anatomy after luminal surgery. In patients with IBD, malnutrition has been associated with poor clinical outcomes, including poor response to biologic therapy, higher rates of hospitalization, increased postoperative complications, and reduced quality of life. While vitamin D, vitamin B12, and iron deficiencies have been well described in the literature, deficiencies in other vitamins and minerals are also common in IBD and can have a significant impact on clinical symptoms and outcomes. Therefore, this review will highlight the importance of these less well studied micronutrients, provide guidelines on assessment and supplementation, and discuss novel testing and treatment strategies.

Prevalence of Zinc Deficiency in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Malabsorptive disorders are closely associated with micronutrient deficiencies. In inflammatory bowel disease (IBD), trace element deficiencies pose a clinical burden from disease onset throughout its course, contributing to morbidity and poor quality of life. We aimed to conduct a systematic review and meta-analysis of the prevalence of zinc deficiency in IBD. Literature screening was performed on six electronic databases until 1 May 2022. Two independent investigators assessed the 152 retrieved articles for inclusion criteria, met by only nine, that included 17 prevalence entries for Crohn’s disease (CD) (n = 9) and ulcerative colitis (UC) (n = 8). No exclusion criteria were applied to language, deficiency cut-offs, population age, general health status, country, or study setting (cohort or cross-sectional). The prevalence of zinc deficiency in blood was scored positive if due to a single disease, not cumulative factors. Zinc deficiency prevalence across selected studies showed higher values in CD than in UC. Pooled analyses by the IBD subgroup showed a total population of 1677 with CD, for an overall mean zinc deficiency prevalence of 54% and 95% confidence intervals (CI) ranging from 0.51 to 0.56, versus 41% (95%CI 0.38–0.45) in the UC population (n = 806). The overall prevalence at meta-analysis was estimated at 50% (95%CI 0.48–0.52), but with high heterogeneity, I2 = 96%. The funnel plot analysis failed to show any evidence of publication bias. The risk of bias across selected studies was moderate to low. In IBD contexts, one of two patients suffers from zinc deficiency. Mismanagement of micronutrient deficiencies plays a role in inflammation trajectories and related cross-pathways. Clinicians in the field are advised to list zinc among trace elements to be monitored in serum.

Prevalence and factors associated with vitamin C deficiency in inflammatory bowel disease.

BACKGROUNDPatients with inflammatory bowel disease (IBD) are prone to several nutritional deficiencies. However, data are lacking on vitamin C deficiency in Crohn’s disease (CD) and ulcerative colitis (UC) patients, as well as the impact of clinical, biomarker and endoscopic disease severity on the development of vitamin C deficiency.AIMTo determine proportions and factors associated with vitamin C deficiency in CD and UC patients.METHODSIn this retrospective study, we obtained clinical, laboratory and endoscopic data from CD and UC patients presenting to the IBD clinic at a single tertiary care center from 2014 to 2019. All patients had an available plasma vitamin C level. Of 353 subjects who met initial search criteria using a cohort discovery tool, 301 ultimately met criteria for inclusion in the study. The primary aim described vitamin C deficiency (≤ 11.4 μmol/L) rates in IBD. Secondary analyses compared proportions with deficiency between active and inactive IBD. Multivariate logistic regression analysis evaluated factors associated with deficiency.RESULTSOf 301 IBD patients, 21.6% had deficiency, including 24.4% of CD patients and 16.0% of UC patients. Patients with elevated C-reactive protein (CRP) (39.1% vs 16.9%, P < 0.001) and fecal calprotectin (50.0% vs 20.0%, P = 0.009) had significantly higher proportions of deficiency compared to those without. Penetrating disease (P = 0.03), obesity (P = 0.02) and current biologic use (P = 0.006) were also associated with deficiency on univariate analysis. On multivariate analysis, the objective inflammatory marker utilized for analysis (elevated CRP) was the only factor associated with deficiency (odds ratio = 3.1, 95% confidence interval: 1.5-6.6, P = 0.003). There was no difference in the presence of clinical symptoms of scurvy in those with vitamin C deficiency and those without.CONCLUSIONVitamin C deficiency was common in IBD. Patients with elevated inflammatory markers and penetrating disease had higher rates of vitamin C deficiency.

HIF1α-Dependent Induction of TFRC by a Combination of Intestinal Inflammation and Systemic Iron Deficiency in Inflammatory Bowel Disease.

Background and Aims: Iron deficiency (ID) is a frequent extra-intestinal manifestation in patients with Inflammatory Bowel Disease (IBD), who often do not respond to iron supplementation. Iron is a cofactor for hydroxylases that suppress the hypoxia-inducible factor-1α (HIF1α), a transcription factor regulating iron homeostasis. We hypothesized that iron deficiency affects mucosal HIF1α activity in IBD. Methods: IBD patients (n = 101) were subdivided based on iron status (ferritin levels or transferrin saturation) and systemic inflammation (C-reactive protein levels). 154 corresponding ileal and colonic biopsies were analyzed for differential expression of 20 HIF1α pathway-associated genes and related to iron and inflammation status. In vitro expression of selected HIF1α pathway genes were analyzed in wild-type and HIF1A-null Caco-2 cells. Results: Gene expression of the mucosal HIF1α pathway was most affected by intestinal location and inflammatory status. Especially, ileal mucosal TFRC expression, encoding the transferrin receptor TFR1, was increased in inflamed tissue (p < 0.001), and further enhanced in ID. Accordingly, TFRC expression in inflamed tissue associated negatively with serum iron levels, which was not observed in the non-inflamed mucosa. The HIF1α pathway agonist DMOG increased TFRC expression in Caco-2 cells, which was blunted in HIF1A-null cells. Conclusion: We demonstrate that inflammation and anatomical location primarily determine HIF1α pathway activation and downstream TFRC expression in the intestinal mucosa. IBD patients with ID may benefit from treatment with HIF1α-agonists by 1) increasing TFRC-mediated iron absorption in non-inflamed tissue and 2) decreasing mucosal inflammation, thereby improving their responsiveness to oral iron supplementation.

Fatigue is a systemic extraintestinal disease manifestation largely independent of disease activity, chronicity, and nutritional deficiencies in inflammatory bowel disease on biologics

Background Fatigue is a common symptom reported by patients with chronic immunoinflammatory diseases and with profound negative implications on health-related quality of life. This study aimed to delineate underlying components contributing to fatigue in patients with inflammatory bowel disease (IBD) receiving biologic therapy. Methods Cross-sectional questionnaire study of all patients with IBD receiving any biologic therapy at a tertiary IBD center. Fatigue was assessed by Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F). Disease activity and quality of life were evaluated by generic questionnaires. Principal component analysis (PCA) was used to identify components of variables explaining fatigue. Results Three hundred patients with IBD were included. Moderate-to-severe fatigue defined as FACIT-F ≤ 39 was present in half of the included patients. PCA condensed variables associated with fatigue into three main components contributing to 49% of observed fatigue. The first component, explaining 21% of fatigue, included factors related to disease chronicity, e.g., long disease duration, high number of previously used biologic therapies, presence of previous intestinal surgery, and increasing age. The second component explained 14% of fatigue and comprised disease activity-related aspects, e.g., disease activity indices and C-reactive protein. The third explained 14% of fatigue and comprised various nutritional deficiencies. Conclusion Fatigue can partly be explained by chronicity, disease activity, and nutritional deficits. However, the cause of fatigue is unexplained in approximately half of the patients with IBD supporting that fatigue can be an independent, systemic extraintestinal disease manifestation in IBD.

P279 Prevalence of iron deficiency in inflammatory bowel disease

Abstract Background Iron deficiency (ID) is one of the most common extraintestinal manifestation of inflammatory bowel disease, which often remains untreated, despite the fact, that ID significantly impairs patients’ quality of life. Since anaemia develops through several pathomechanisms (e.g., occult bleeding, chronic inflammation, medicines), treating anaemia requires to manage the underlying pathological changes as well. Methods In our prospective, two-centers study, we assessed the frequency of ID among our IBD patients. The diagnosis of iron deficiency (iron deficiency anaemia [IDA], anaemia of chronic inflammation [CDA], anaemia of mixed origin [AMO]) was based on the ECCO’s anaemia guideline. According to the guideline, haemoglobin, CRP, ferritin, transferrin saturation, serum iron values, total iron binding capacity, hematocrit, and platelet counts were collected from our patients on a one-off basis. We aimed to compare the frequency of ID in a biologic centre, and in a non-biologic centre hospital as well. In addition, we assessed the frequency of the need for oral and intravenous iron replacement, respectively, based on the guideline as well. Results 720 patients were included in our study (CD 58.8%, UC 41.2 %). Average age was 43.3 years. We found, that 26.6% of our patients had anemia. There was no significant difference in the prevalence of ID (p=0.65) between CD and UC patients. Based on the ECCO criteria, 61.8% of them have ID (33.0% IDA, 23.0% AMO, 5.8% CDA), and in the rest of the cases (38.2%) it was classified to be anaemia of other origin (AOO), however, in 68.5% of these cases ID can be suspected at some degree, as ferritin was &amp;lt; 100 mg/l and/or transferrin saturation ≤ 20%. In total, 133 patients (69.6%) had anaemia in remission, and 58 patients (30.4%) in case of activity (CRP ≥10 mg/l). In addition, we found an association between elevated CRP levels and the prevalence/severity of anemia (p&amp;lt;0.001) as mean CRP was 5.9 mg/l in the non-anaemic, 9.9 mg/l in the anaemic, and 16.0 mg/l in the severe anaemic group. Anemia (p&amp;lt;0.001) and iron deficiency anemia (p&amp;lt;0.001) were significantly more common in patients treated in a clinical/biological centre, compared to a non-biological hospital. Patients with active disease received iv. ferric-carboximaltose, which turned to be efficient (Hgb&amp;gt;120–130 g/l) already after 2 months in 76.5% of the cases. Conclusion Based on our results, anemia and iron deficiency are common complications of IBD and correlate well with disease activity. Consequently, we suggest, that iron deficiency should be a part of the treat to target approach, and in case of ID, iv. ferric-carboximaltose is efficient in activity as well.

Iron Deficiency Anemia in Inflammatory Bowel Diseases-A Narrative Review.

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is characterized by chronic inflammation of the gastrointestinal tract. IBD has been associated with numerous symptoms and complications, with the most common being iron deficiency anemia (IDA). Iron deficiency in IBD is caused by inadequate intake, malabsorption (including duodenal involvement and surgical removal), and chronic blood loss by mucosal ulcerations. Therefore, an appropriate diet should be enforced. Iron deficiency and iron supplementation have been associated with alterations to gut microbiota. IBD-associated anemia, in particular iron deficiency anemia, is associated with a significant decrease in quality of life and with clinical symptoms such as chronic fatigue, headaches and dizziness, reduced exercise tolerance, pale skin, nails, conjunctiva, and fainting. However, despite these numerous adverse symptoms, IDA remains undertreated. The European Crohn’s and Colitis Organisation (ECCO) guidelines state that patients should be monitored for anemia. Adequate treatment, whether oral or intravenous, should be implemented while taking into consideration C-reactive protein values (CRP), hemoglobin levels, and therapeutic response. It should be stressed that every case of anemia in IBD patients should be treated. Intravenous iron formulations, which are more superior compared to the oral form, should be used. There is a need to increase awareness and implementation of international guidelines on iron supplementation in patients with IBD.

Risk Factors for Vitamin D Deficiency in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

To identify risk factors for hypovitaminosis D in inflammatory bowel disease and conduct a comprehensive systematic review with meta-analysis to quantify the impact on vitamin D deficiency. We conducted a literature search of studies through PubMed, Embase, Cochrane Library, and Web of Science. In addition, relevant articles were searched manually. Studies were included if the odds ratios (OR) and 95% CI of each risk factor were reported or could be calculated. We will use the fixed-effects or random-effects model to estimate the pooled effect. Out of 1018 articles, 25 eligible studies were identified, including 5826 participants. The risk factors associated with hypovitaminosis D were non-Caucasian (OR: 3.79, 95% CI: 2.68-5.34), Crohn's disease (OR: 1.38, 95% CI: 1.21-1.56), disease activity (OR: 1.85, 95% CI: 1.61-2.13), inflammatory bowel disease-related surgery (OR: 1.61, 95% CI: 1.38-1.89), exposure to steroid (OR: 1.61, 95% CI: 1.28-2.03), and biologics (OR: 1.78, 95% CI: 1.48-2.14). In 30 ng/mL and adjusted OR subgroup, male (OR: 1.84, 95% CI: 1.47-2.31) and winter season (OR: 2.49, 95% CI: 1.69-3.67) also were risk factors, respectively. 5-aminosalicylic acid (OR: 1.10, 95% CI: 0.74-1.63) and smoking (OR: 1.19, 95% CI: 0.98-1.45) were unrelated to vitamin D deficiency. For vitamin D deficiency in inflammatory bowel disease, non-Caucasian, Crohn's disease, disease activity, surgery, exposure to steroid and biologics, males are risk factors, while 5-aminosalicylic acid and smoking are not. The relationship between body mass index, winter season, exposure to immunomodulators, and vitamin D deficiency remains unclear.

P658 Is vitamin D deficiency related to fat malabsorption or inflammation in Inflammatory Bowel Disease? Preliminary results from the Fat-D study

Abstract Background Vitamin D deficiency is highly prevalent in patients with inflammatory bowel disease (IBD). The question of whether vitamin D status is a contributory factor or a consequence of IBD, or maybe both, remains unanswered, and is confounded by the complexity of inflammation, IBD and vitamin D. Fat malabsorption has been proposed as a possible reason for deficiencies of vitamin D in IBD. The aim of this study was to further understanding of vitamin D deficiency in IBD by investigating possible causal relationships of fat malabsorption and inflammation on vitamin D levels in this complex context. Methods In a comparative, cross-sectional study in IBD patients, 25(OH)D was analysed by LCMS/MS. Serum β-carotene levels were used as a biomarker for fat malabsorption. Vitamin K1, another fat-soluble vitamin, was used to affirm a possible causative relation between β-carotene and vitamin D in case of fat malabsorption. β-carotene and vitamin K were measured in serum by HPLC. Inflammation was characterised by serum hsCRP&amp;lt;5mg/L. Results 51 IBD patients (30f;20CD/18UC;45.3±16.3y; 21 with inflammatory activity) were enrolled. In patients with vs. without inflammation, serum 25(OH)D levels were significantly lower (26.5±14.6ng/mL vs. 36.8±12.6ng/mL, p&amp;lt;0.05), while serum vitamin K1 (1.4±0.5µg/L vs. 1.2±0.4µg/L) and β-carotene (28.5±0.6.0µg/dL vs. 35.9±5.4µg/dL) levels were similar (p&amp;gt;0.05). 36/51 of the patients had low serum β-carotene levels, indicating steatorrhoea. Neither 25(OH)D (32.1.5±13.8ng/mL vs. 33.6±15.8ng/mL) nor vitamin K1 (1.3±0.5µg/L vs. 1.2±0.4µg/L) levels differed according to the presence vs. absence of steatorrhoea (p&amp;gt;0.05). Similarly, no correlation was found for 25(OH)D (r=0.024, p=0.875) or serum vitamin K1 (r=0.111, p=0.462) with β-carotene levels. On the other hand, 25(OH)D levels were significantly inversely correlated with hsCRP (r=-0.338, p=0.015), whereas vitamin K1(r=0.050, p=0.731) and β-carotene (r=-0.118, p=0.438) did not show a similar relation. Conclusion Vitamin D levels were confirmed to be related to inflammation in IBD. A lack of correlation with fat malabsorption, as indicated by β-carotene levels, or with steatorrhoea, was found for vitamin D and confirmed by measuring and comparing serum levels of an additional fat-soluble vitamin, K1. We conclude that low vitamin D levels in patients with IBD are related to inflammation rather than fat malabsorption.

Inflammatory Bowel Disease and Vitamin D

Vitamin D contributes to bone metabolism and acts as an immune modulator for both innate and adaptive immunity. The serum level of vitamin D has been associated with inflammatory diseases, such as inflammatory bowel disease (IBD). In epidemiologic studies, IBD patients have been shown to have low levels of vitamin D. The suboptimal circulating levels of vitamin D in IBD patients may be caused by low exposure to sunlight, dietary malabsorption, and the impaired conversion of active metabolites (1,25[OH]2D). Recent studies have demonstrated that vitamin D deficiency in IBD can increase the chance of disease recurrence, IBD-related hospitalization or surgery, and deterioration of quality of life. Supplementation with vitamin D is therefore thought to reduce the risk of flare-ups and the improvement of the quality of life in IBD patients. This review aims to summarize the latest knowledge on the effects of vitamin D deficiency on IBD and the possible benefits of vitamin D supplementation in IBD patients.

Biomarkers and Hematological Indices in the Diagnosis of Iron Deficiency in Children with Inflammatory Bowel Disease.

Inflammation may affect many routinely available parameters of iron homeostasis. Thus, the recognition of iron deficiency in inflammatory bowel disease (IBD) remains a diagnostic challenge in a clinical routine. The aim of the study was to detect the most efficient marker of iron deficiency in IBD children. In a group of 75 IBD children, we evaluated the sensitivity, specificity, accuracy, and positive and negative predictive values of erythrocytes’ indices, including MCV, MCH, MCHC and RDW, and biochemical markers, including iron, transferrin, sTfR and sTfR/log ferritin, for identifying iron deficiency. Receiver operating characteristic (ROC) analysis was used to compare the ability of these parameters to detect iron deficiency. The best predictors of iron deficiency were sTfR/log ferritin, with accuracy 0.86, sensitivity 0.98, specificity 0.63, positive predictive value 0.83 and negative predictive value 0.94, and sTfR, with accuracy 0.77, sensitivity 0.82, specificity 0.67, positive predictive value 0.82 and negative predictive value 0.67. Moreover, sTfR/log ferritin exhibited the largest area under ROC (0.922), followed by sTfR (0.755) and MCH (0.720). The sTfR/log ferritin index appears to be the most efficient marker of iron depletion in pediatric IBD, and it may give an added value in the management of IBD patients.

P144 Vitamin C deficiency in inflammatory bowel disease: the forgotten micronutrient

Abstract Background Micronutrient deficiencies are common in patients with inflammatory bowel disease (IBD). To date, the majority of the literature has focused on vitamin D, vitamin B12, and iron deficiencies. We report a case series of patients with IBD and vitamin C deficiency. Methods We performed a retrospective chart review of 20 patients with IBD who had vitamin C deficiency (defined as a level ≤0.2 mg/dl) treated in a single tertiary care centre from February 2018 to October 2019. Demographics as well as disease characteristics and laboratory data were collected. In addition, data from routine nutritional assessments, performed by a nutritionist, were also included. Results Of these 20 patients, 11 (55%) were female with a median age of 27.5 years. Fifteen (75%) had Crohn’s disease (CD) and 5 (25%) had Ulcerative colitis (UC). Ten (50%) had been diagnosed with IBD within the last 3 years, and 10 (50%) had a duration of disease &amp;gt;5 years. Disease location was L1 ileal in 6 (30%) patients, L2 colonic in 5 (25%) and L3 ileocolonic in 9 (45%); behaviour was B1 non-stricturing, non-penetrating in 10 (50%) patients, B2 stricturing in 7 (35%) and B3 penetrating in 3 (15%). Nine (45%) patients had previous history of surgery. At the time of the study, 13 (87%, N=15) CD patients had a Harvey–Bradshaw Index &amp;gt;5, and 3 (60%, N = 5) UC patients had a Partial Mayo Score 5–7, indicating active disease. Overall, 14 (70%) patients were on biologic therapy. Sixteen (80%) patients had symptoms consistent with clinical scurvy, including 9 (45%) arthralgia, 6 (30%) dry brittle hair with hair loss, 4 (20%) pigmented rash, 3 (15%) gingivitis, 2 (10%) easy bruising and 1 (5%) brittle nails. Six (32%) had 3 or more of these clinical manifestations. Of those who underwent a nutrition evaluation (N = 18), 10 (56%) reported avoidance of all fruits and vegetables and 3 (17%) reported a reduction of fruits and vegetables in their diet. While all patients experienced vitamin C deficiency, some also had concomitant vitamin D, vitamin B12, iron and ferritin deficiencies (Table 1). Conclusion Vitamin C deficiency can occur in IBD patients and is associated with clinical symptoms of scurvy. Prospective studies are needed to evaluate prevalence of vitamin C deficiency in IBD and its ultimate impact on clinical outcomes. Meanwhile this study emphasises the need for appropriate dietary counselling in patients with IBD.

P309 Ferritin or transferrin saturation vs. soluble transferrin receptor for iron deficiency diagnosis in inflammatory bowel disease

Abstract Background Iron deficiency is common in inflammatory bowel disease (IBD) and can negatively affect the quality of life even in the absence of anaemia. Diagnosis of iron deficiency is based on ferritin and transferrin saturation (TfS) in routine practice, yet guideline thresholds are not evidence-based. Serum levels of soluble transferrin receptor (sTfR) are the best non-invasive test as it is not influenced by inflammation, but the test is costly with low availability. Thus, the aim of this study was to evaluate for the first time the accuracy of ferritin and/or TfS for diagnosing iron deficiency in IBD and identify the optimal thresholds of these parameters using sTfR as the gold standard. Methods Serum samples were collected from IBD patients (n = 2,072) receiving a biologic in routine practice. Diagnostic accuracy was assessed using receiver operating characteristic curves for ferritin and TfS levels separately or combined. Results No ferritin or TfS threshold had good diagnostic performance in CD patients. In UC patients with CRP &amp;lt;10 mg/l, optimal iron deficiency diagnostic performances were observed with ferritin and TfS thresholds of 65 µg/l and 16%, respectively. For UC patients with CRP &amp;gt;10 mg/l, the thresholds with the best diagnostic performance were 80 µg/l for ferritin and 11% for TfS. There was no added value for combined ferritin and TfS. Conclusion In conclusion, we found that ferritin and TfS are reliable parameters for iron deficiency diagnosis only in UC patients, at thresholds different from current guidelines. In CD patients, sTfR should be used given the poor diagnostic performance of ferritin and TfS.

Curcumin induces mild anemia in a DSS-induced colitis mouse model maintained on an iron-sufficient diet.

Anemia is frequently encountered in patients with inflammatory bowel disease (IBD), decreasing the quality of life and significantly worsening the prognosis of the disease. The pathogenesis of anemia in IBD is multifactorial and results mainly from intestinal blood loss in inflamed mucosa and impaired dietary iron absorption. Multiple studies have proposed the use of the polyphenolic compound curcumin to counteract IBD pathogenesis since it has significant preventive and therapeutic properties as an anti-inflammatory agent and very low toxicity, even at high dosages. However, curcumin has been shown to possess properties consistent with those of an iron-chelator, such as the ability to modulate proteins of iron metabolism and decrease spleen and liver iron content. Thus, this property may further contribute to the development and severity of anemia of inflammation and iron deficiency in IBD. Herein, we evaluate the effects of curcumin on systemic iron balance in the dextran sodium sulfate (DSS) model of colitis in C57Bl/6 and BALB/c mouse strains that were fed an iron-sufficient diet. In these conditions, curcumin supplementation caused mild anemia, lowered iron stores, worsened colitis and significantly decreased overall survival, independent of the mouse strain. These findings suggest that curcumin usage as an anti-inflammatory supplement should be accompanied by monitoring of erythroid parameters to avoid exacerbation of iron deficiency anemia in IBD.

Review article: treating-to-target for inflammatory bowel disease-associated anaemia.

Iron deficiency has a high prevalence in inflammatory bowel disease (IBD) patients, with negative impact on quality of life and work capacity. To propose an innovative approach based on early intervention, treating to target and tight monitoring in the management of iron deficiency in IBD patients. We conducted a literature review on PubMed and Medline using pre-defined keywords and terms to identify relevant studies on iron deficiency in IBD. Many physicians are focused on treating anaemia; however, anaemia is one of the consequences of iron deficiency. Hence, our therapeutic goal for these patients should evolve towards prevention of anaemia by screening and treating iron deficiency. Early diagnosis of iron deficiency is based on a combination of ferritin concentration and transferrin saturation. We consider that normalisation of these biomarkers reflects iron stores replenishment and should be considered as a major therapeutic goal. Treating iron deficiency regardless of the presence of anaemia seems to improve quality of life in several chronic conditions and should be considered as an innovative approach in IBD although strong evidence is still lacking. Tight monitoring is required to allow early detection of iron deficiency recurrence and to consider prompt additional iron supplementation. We propose to extrapolate a three-step strategy (early detection and intervention, treating-to-target and tight monitoring) to the management of iron deficiency in IBD patients. Universally applied, this proactive approach is expected to result in better outcomes in IBD patients.

Vitamin D in inflammatory bowel disease: more than just a supplement.

The aim of this review is to explore the protective role of vitamin D on the gastrointestinal tract, summarize the epidemiology of vitamin D deficiency in inflammatory bowel disease (IBD), and highlight recent studies examining the impact of low vitamin D and vitamin D supplementation on IBD clinical outcomes. Vitamin D protects the gut barrier by regulating tight junction proteins and inhibiting intestinal apoptosis. Vitamin D enhances innate immunity by inducing antimicrobial peptides and regulates adaptive immunity by promoting anti-inflammatory T cells and cytokines. Vitamin D may also alter the gut microbiota. The prevalence of vitamin D deficiency in IBD is 30-40%. Predictors of vitamin D deficiency in IBD include non-white ethnicity, IBD-related surgery, BMI more than 30, female sex, and pregnancy. Low vitamin D is associated with increased disease activity, inflammation, and clinical relapse. The effect of vitamin D supplementation on IBD clinical outcomes is inconclusive. Vitamin D plays a protective role on gut health. Vitamin D deficiency in IBD is prevalent and associated with poor outcomes. The benefits of vitamin D supplementation in IBD is unclear. Measuring novel vitamin D metabolites and vitamin D absorption in IBD patients may help guide future studies.

SHIP1 Deficiency in Inflammatory Bowel Disease Is Associated With Severe Crohn's Disease and Peripheral T Cell Reduction.

In our previous study, we observed a severe reduction in the Src homology 2-containing-inositol-phosphatase-1 (SHIP1) protein in a subpopulation of subjects from a small adult Crohn’s Disease (CD) cohort. This pilot study had been undertaken since we had previously demonstrated that engineered deficiency of SHIP1 in mice results in a spontaneous and severe CD-like ileitis. Here, we extend our analysis of SHIP1 expression in peripheral blood mononuclear cells in a second much larger adult Inflammatory Bowel Disease (IBD) cohort, comprised of both CD and Ulcerative Colitis patients, to assess contribution of SHIP1 to the pathogenesis of human IBD. SHIP1 protein and mRNA levels were evaluated from blood samples obtained from IBD subjects seen at UCSF/SFVA, and compared to healthy control samples. Western blot analyses revealed that ~15% of the IBD subjects are severely SHIP1-deficient, with less than 10% of normal SHIP1 protein present in PBMC. Further analyses by flow cytometry and sequencing were performed on secondary samples obtained from the same subjects. Pan-hematolymphoid SHIP1 deficiency was a stable phenotype and was not due to coding changes in the INPP5D gene. A very strong association between SHIP1 deficiency and the presence of a novel SHIP1:ATG16L1 fusion transcript was seen. Similar to SHIP1-deficient mice, SHIP1-deficient subjects had reduced numbers of circulating CD4+ T cell numbers. Finally, SHIP1-deficient subjects with CD had a history of severe disease requiring multiple surgeries. These studies reveal that the SHIP1 protein is crucial for normal T cell homeostasis in both humans and mice, and that it is also a potential therapeutic and/or diagnostic target in human IBD.