Dietary triggers of gut inflammation following exclusive enteral nutrition in children with Crohn's disease: a pilot study.

BACKGROUND: The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn's disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition. METHODS: Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn's disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis. RESULTS: Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median [Q1, Q3], g/day; Fibre: 12.1 [11.2, 19.9] vs. 9.9 [7.6, 12.1], p = 0.03; Red and processed meat: 151 [66.7, 190] vs. 63.3 [21.7, 67], p = 0.02; gluten-containing cereals: 289 [207, 402] vs. 203 [61, 232], p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups. CONCLUSIONS: This pilot study identified potential dietary triggers of gut inflammation in children with Crohn's disease after food reintroduction following treatment with exclusive enteral nutrition. TRIAL REGISTRATION: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).

Micronutrient deficiencies in children with coeliac disease; a double-edged sword of both untreated disease and treatment with gluten-free diet.

INTRODUCTION: In coeliac disease (CD) micronutrient deficiencies may occur due to malabsorption in active disease and diminished intake during treatment with a gluten-free diet (GFD). This study assessed the micronutrient status in children with CD at diagnosis and follow-up. METHODS: Fifteen micronutrients were analysed in 106 blood samples from newly diagnosed CD and from patients on a GFD for <6 months, 6-12 months and with longstanding disease (>12 months). Predictors of micronutrient status included: demographics, disease duration, anthropometry, gastrointestinal symptoms, raised tissue transglutaminase antibodies (TGA), multivitamin use and faecal gluten immunogenic peptide (GIP). Micronutrient levels were compared against laboratory reference values. RESULTS: At CD diagnosis (n = 25), low levels in ≥10% of patients were observed for: vitamins E (88%), B1 (71%), D (24%), K (21%), A (20%) and B6 (12%), ferritin (79%), and zinc (33%). One year post-diagnosis, repletion of vitamins E, K, B6 and B1 was observed (<10% patients). In contrast, deficiencies for vitamins D, A and zinc did not change significantly post-diagnosis. Copper, selenium and magnesium did not differ significantly between diagnosis and follow-up. All samples for B2, folate, vitamin C (except for one sample) and B12 were normal. A raised TGA at follow-up was associated with low vitamins A and B1 (raised vs normal TGA; vitamin A: 40% vs 17%, p = 0.044, vitamin B1: 37% vs 13%, p = 0.028). Low vitamin A (p = 0.009) and vitamin D (p = 0.001) were more common in samples collected during winter. There were no associations between micronutrient status with GIP, body mass index, height, socioeconomic status, or gastrointestinal symptom. Multivitamin use was less common in patients with low vitamin D. CONCLUSIONS: Several micronutrient deficiencies in CD respond to a GFD but others need to be monitored long-term and supplemented where indicated.

Ferric Carboxymaltose Across All Ages in Paediatric Gastroenterology Shows Efficacy Without Increased Safety Concerns.

OBJECTIVES: The aim of the study was to assess the efficacy, safety and side-effect profile of ferric carboxymaltose (FCM) for correcting IDA in children and adolescents in paediatric gastroenterology, hepatology, and nutrition. METHOD: This was a retrospective study of all gastroenterology patients <18 years who had FCM (October 2015 to October 2017). Haematological and biochemical parameters were recorded pre-infusion, at 4 weeks, 3 months, 6 months, and 1 year post-infusion. Recognised side-effects were documented. RESULTS: Sixty-six children received FCM during this period. Data was analysed on 61 children, 5 excluded because of inadequate data. The median age at administration was 14 years (IQR 7). Thirty-two (52%) were boys. Twenty-six (42%) were <14 years old. Seven (11.5%) were <5 years old. Seventeen (28%) were switched from oral iron supplements to FCM. The median dose of FCM delivered was 19 mg/kg. The median haemoglobin increased from 108 to 126 g/L at 1 month post-infusion (P value <0.00001). The mean cell volume also improved from 80 to 84 fL at 1 month post-infusion (P value = 0.0007). Forty-eight (94%) children corrected their anaemia after receiving FCM. Two patients (3%) reported side-effects with skin bruising and staining. CONCLUSIONS: FCM appears to be effective in correcting IDA in children across a wide range of gastroenterology indications and all ages. It is effective and generally well tolerated including in very young patients. Potential side-effects can be avoided by careful monitoring during infusions.

Alterations in Intestinal Microbiota of Children With Celiac Disease at the Time of Diagnosis and on a Gluten-free Diet.

BACKGROUND AND AIMS: It is not clear whether alterations in the intestinal microbiota of children with celiac disease (CD) cause the disease or are a result of disease and/or its treatment with a gluten-free diet (GFD). METHODS: We obtained 167 fecal samples from 141 children (20 with new-onset CD, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with CD) in Glasgow, Scotland. Samples were analyzed by 16S ribosomal RNA sequencing, and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 children with new-onset CD after 6 and 12 months on a GFD. Relationships between microbiota with diet composition, gastrointestinal function, and biomarkers of GFD compliance were explored. RESULTS: Microbiota α diversity did not differ among groups. Microbial dysbiosis was not observed in children with new-onset CD. In contrast, 2.8% (Bray-Curtis dissimilarity index, P = .025) and 2.5% (UniFrac distances, P = .027) of the variation in microbiota composition could be explained by the GFD. Between 3% and 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to CD with high diagnostic probability. Most operational taxonomic units that differed between patients on a GFD with new-onset CD vs healthy children were associated with nutrient and food group intake (from 75% to 94%) and with biomarkers of gluten ingestion. Fecal levels of butyrate and ammonia decreased during the GFD. CONCLUSIONS: Although several alterations in the intestinal microbiota of children with established CD appear to be effects of a GFD, specific bacteria were found to be distinct biomarkers of CD. Studies are needed to determine whether these bacteria contribute to pathogenesis of CD.

Prehabilitation: The Impact of Preoperative Exclusive Enteral Nutrition on Paediatric Patients With Crohn Disease.

Exclusive enteral nutrition (EEN) is effective in inducing remission in paediatric Crohn Disease (CD) and has been shown to reduce inflammation and improve outcomes in adult CD patients when used before resectional surgery. This retrospective study demonstrates that preoperative EEN is achievable in paediatric CD patients undergoing right hemicolectomy and is associated with positive peri-operative outcomes. Seventeen patients (8 who received preoperative EEN and 9 who did not) were included in the study. Six of 8 (75.0%) managed EEN orally; 1 via nasogastric tube and another via a previously sited gastrostomy. Use of preoperative EEN was associated with a decreased rate of moderate/severe disease on resection pathology (5/8 [62.5%] vs 9/9 [100%]; P = 0.04). Larger studies are required to determine the wider potential benefits of preoperative EEN on postoperative outcomes within paediatric practice.

The reduction of faecal calprotectin during exclusive enteral nutrition is lost rapidly after food re-introduction.

BACKGROUND: Faecal calprotectin decreases during exclusive enteral nutrition in children with active Crohn's disease. It is unknown how faecal calprotectin changes during food re-introduction and the influence of maintenance enteral nutrition. AIMS: To study changes to faecal calprotectin during exclusive enteral nutrition and at food reintroduction, and explore associations with maintenance enteral nutrition. METHODS: Children with Crohn's disease were followed during exclusive enteral nutrition and during food-reintroduction. Faecal calprotectin was measured before, at 33 and 54 days of exclusive enteral nutrition, and at 17, 52 and 72 days after food-reintroduction. Maintenance enteral nutrition use was recorded with estimated weight food diaries. Data are presented with medians and Q1:Q3. RESULTS: Sixty-six patients started exclusive enteral nutrition and 41 (62%) achieved clinical remission (weighted paediatric Crohn's disease activity index <12.5). Baseline faecal calprotectin (mg/kg) decreased after 4 and 8 weeks of exclusive enteral nutrition (Start: 1433 [Q1: 946, Q3: 1820] vs 33 days: 844 [314, 1438] vs 54 days: 453 [165, 1100]; P < .001). Within 17 days of food reintroduction, faecal calprotectin increased to 953 [Q1: 519, Q3: 1611] and by 52 days to 1094 [660, 1625] (both P < .02). Fifteen of 41 (37%) children in remission used maintenance enteral nutrition (333 kcal or 18% of energy intake). At 17 days of food reintroduction, faecal calprotectin was lower in maintenance enteral nutrition users than non-users (651 [Q1: 271, Q3: 1781] vs 1238 [749, 2102], P = .049) and correlated inversely with maintenance enteral nutrition volume (rho: -0.573, P = .041), kcals (rho: -0.584, P = .036) and % energy intake (rho: -0.649, P = .016). Maintenance enteral nutrition use was not associated with longer periods of remission (P = .7). Faecal calprotectin at the end of exclusive enteral nutrition did not predict length of remission. CONCLUSIONS: The effect of exclusive enteral nutrition on faecal calprotectin is diminished early during food reintroduction. Maintenance enteral nutrition at ~18% of energy intake is associated with a lower faecal calprotectin at the early phase of food reintroduction but is ineffective in maintaining longer term remission.

Role for structured telephone clinics in paediatric gastroenterology: reflections, lessons and patient feedback.

BACKGROUND: Telephone clinics have been established within our department to try and improve communication with families, limit waiting times and help face-to-face clinics run more efficiently. As part of the ongoing care needs for our patients and families it was felt important to determine if telephone clinics were meeting the needs of the young person and family as well as those of the health professional. OBJECTIVE: To assess the effects of a structured consultant delivered telephone clinic. METHOD: Data were collected regarding patients who had a consultant telephone appointment between July 2016 and March 2017. Data collected include demographics and appointment reason. An evaluation questionnaire was sent to all parent/carer(s). RESULTS: 25 clinics comprising 194 contacts, including 34 duplicate contacts. 120 questionnaires sent. 7/160 (4.3%) were new patients. The main contact reason was biopsy results after endoscopy (93/180; 52%). Failure to attend rate was significantly lower at 18/194 (9.2%) compared with failure to attend rate of 52/240 (21.6%) for a traditional clinic (p<0.001). 40/120 (33%) returned completed questionnaires, 25/40 (68.4%) reported the reason for appointment was test results. Travel time and school attendance were identified as main advantages. Mean parental rating score for the service was 8/10 with 21/40 (54%) scoring the service as 10/10. CONCLUSION: The initial results of this audit are promising. Structured telephone appointments have a key role in delivering patient care in paediatric gastroenterology and have benefits to health professional, parent/carer and patients. These clinics have now been widely adopted by all members of our department.

Treatment of Active Crohn's Disease With an Ordinary Food-based Diet That Replicates Exclusive Enteral Nutrition.

BACKGROUND & AIMS: Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD. METHODS: We evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment. RESULTS: For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and the short-chain fatty acids (µmol/g) acetate (decrease 27.4 ± 22.6 vs 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log10 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN [P = .015] and 1.0 for CD-TREAT [P = .044] vs chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; P = .002). CONCLUSION: CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. ClinicalTrials.gov, numbers NCT02426567 and NCT03171246.

Comparison of Clinical Methods With the Faecal Gluten Immunogenic Peptide to Assess Gluten Intake in Coeliac Disease.

OBJECTIVES: Detection of faecal gluten immunogenic peptides (GIP) is a biomarker of recent gluten consumption. GIP levels can be used to monitor gluten intake and compliment clinical methods to evaluate compliance to gluten-free diet (GFD). In the present study, recent gluten intake was measured by GIP in children with coeliac disease (CD) and compared to routine clinical measures to evaluate GFD compliance. METHODS: GIP was measured in 90 samples from 63 CD children (44 previously and 19 newly diagnosed with follow-up samples at 6 and 12 months on GFD). Compliance to GFD was evaluated based on clinical assessment, tissue transglutaminase (tTG) levels, and Biagi score. RESULTS: GIP was detectable in 16% of patients with previous CD diagnosis on GFD. Body mass index z score (P = 0.774), height z score (P = 0.723), haemoglobin concentration (P = 0.233), age (P = 0.448), sex (P = 0.734), or disease duration (P = 0.488) did not differ between those with detectable and nondetectable GIP. In newly diagnosed patients, on gluten-containing diet, GIP was detectable in 95% of them. Following GFD initiation, GIP decreased (P < 0.001); 17% and 27% had detectable levels at 6 and 12 months, respectively. Compared to GIP, the Biagi score, tTG, and clinical assessment presented sensitivity of 17%, 42%, and 17%, respectively. Likewise, GIP was detectable in 16%, 16%, and 14% of patients evaluated as GFD compliant according to the Biagi score, tTG, and clinical assessment, respectively. A combination of methods did not improve identification of patients who were noncompliant. CONCLUSIONS: Inclusion of faecal GIP measurements is likely to improve identification of GFD recent noncompliance in CD management and could be incorporated into current follow-up strategies.

Dietitians' perceptions and experience of blenderised feeds for paediatric tube-feeding.

OBJECTIVE: There is an emerging interest in the use of blenderised food for tube-feeding (BFTF). This survey explored paediatric dietitians' perceptions and experiences of BFTF use. DESIGN: A web-based questionnaire was distributed to the Paediatric group of the British Dietetic Association. The survey captured dietitians' personal opinions and experience supporting children on BFTF, and the perceptions of carers. RESULTS: Of the 77 respondents, 19 were aware of professional guidelines and 63 had never received training on BFTF. Thirty-four would not recommend BFTF and 11 would advise against its use; yet 43 would recommend it to supplement commercial feeds. Fifty-seven would change their perception about BFTF if there were evidence-based guidelines. Forty-four would feel confident to support a patient using BFTF. Forty-three had previous experience supporting a patient with BFTF. The main concerns perceived by dietitians, pertinent to the use of BFTF, were nutritional inadequacy (n=71), tube blockages (n=64) and increased infection risk (n=59) but these were significantly higher than those experienced by themselves in clinical practice (p<0.001 for all three). A reduction in reflux and vomiting and increased carer involvement were the main perceived and observed benefits by both dietitians and carers. CONCLUSIONS: The use of these feeds for tube-fed children is increasingly being seen as a viable choice. Dietitians experienced significantly fewer issues with the use of BFTF in clinical practice compared with their self-reported apprehensions in the survey. Well-controlled studies are now needed to objectively assess the benefits, risks, costs and practicality of BFTF.

Nutritional status, growth and disease management in children with single and dual diagnosis of type 1 diabetes mellitus and coeliac disease.

BACKGROUND: The consequences of subclinical coeliac disease (CD) in Type 1 diabetes mellitus (T1DM) remain unclear. We looked at growth, anthropometry and disease management in children with dual diagnosis (T1DM + CD) before and after CD diagnosis. METHODS: Anthropometry, glycated haemoglobin (HbA1c) and IgA tissue transglutaminase (tTg) were collected prior to, and following CD diagnosis in 23 children with T1DM + CD. This group was matched for demographics, T1DM duration, age at CD diagnosis and at T1DM onset with 23 CD and 44 T1DM controls. RESULTS: No differences in growth or anthropometry were found between children with T1DM + CD and controls at any time point. Children with T1DM + CD, had higher BMI z-score two years prior to, than at CD diagnosis (p < 0.001). BMI z-score change one year prior to CD diagnosis was lower in the T1DM + CD than the T1DM group (p = 0.009). At two years, height velocity and change in BMI z-scores were similar in all groups. No differences were observed in HbA1c between the T1DM + CD and T1DM groups before or after CD diagnosis. More children with T1DM + CD had raised tTg levels one year after CD diagnosis than CD controls (CDx to CDx + 1 yr; T1DM + CD: 100% to 71%, p = 0.180 and CD: 100% to 45%, p < 0.001); by two years there was no difference. CONCLUSIONS: No major nutrition or growth deficits were observed in children with T1DM + CD. CD diagnosis does not impact on T1DM glycaemic control. CD specific serology was comparable to children with single CD, but those with dual diagnosis may need more time to adjust to gluten free diet.

A retrospective study showing maintenance treatment options for paediatric CD in the first year following diagnosis after induction of remission with EEN: supplemental enteral nutrition is better than nothing!

BACKGROUND: A limited body of research suggests that ongoing maintenance enteral nutrition (MEN) can be beneficial in maintaining disease remission in Crohn's Disease (CD). We aimed to assess how achievable MEN is and whether it helps to prolong remission. METHODS: Patients newly diagnosed with CD in 2010 and 2011 who commenced exclusive enteral nutrition (EEN) for 8 weeks were followed up for a year post diagnosis. All patients who took EEN were encouraged to continue MEN post EEN. Data on azathioprine use was also collected. Categorical variables were compared using chi-square/Fischer's exact test. Medians were expressed along with complete data ranges. RESULTS: 59 patients (34 male, median age 11.07 years, range 2.5-16.33 years) were identified. 11/59 (18%) had a poor response to EEN and were switched to steroids. 48/59 patients completed 8 weeks EEN and achieved clinical remission/response. 46/48 patients received Modulen IBD®, 29/48 (60%) consumed EEN orally and 19/48 (40%) via NGT. 15/48 (31%) patients were able to continue MEN post EEN completion. MEN was consumed for a mean of 10.8 months (range 4-14 months). 14/15 patients drank MEN and 1/15 had MEN via NGT. Remission rates at 1 year in patients continuing MEN were 60% (9/15) compared to 15% (2/13) in patients taking no treatment (p = 0.001) and 65% (13/20) in patients taking azathioprine (p = 0.14). CONCLUSION: A sub group of patients can continue MEN as a maintenance treatment and this seems a useful strategy, especially in those who are not commencing azathioprine.

Selection and identification of autochthonous potential probiotic bacteria from turbot larvae (Scophthalmus maximus) rearing units.

The purpose of this study was to select, identify and characterise bacteria as a disease control measure in the rearing of marine fish larvae (turbot, Scophthalmus maximus). Thirty-four out of 400 marine bacterial strains exhibited in vitro anti-bacterial activity against three fish larval pathogens. Two strains originated from culture collections and thirty two strains were isolated directly from turbot larvae rearing units using a pre-selection procedure to facilitate detection of antagonists. Approximately 8,500 colonies from colony-count plates were replica-plated on agar seeded with Vibrio anguillarum, and 196 of them caused zones of clearing in the V. anguillarum agar layer. Of these, 32 strains exhibited reproducible antibacterial properties in vitro when tested against the fish pathogens V. anguillarum 90-11-287, V. splendidus DMC-1 and a Pseudoalteromonas HQ. Seventeen antagonists were identified as Vibrio spp. and four of twelve tested were lethal to yolk-sac larvae. The 15 remaining strains were identified as Roseobacter spp. based on phenotypic criteria and 16S rDNA gene sequence analysis of two strains representing the two major RAPD groups. Most of the remaining 164 strains selected in the initial replica plating were identified as Vibrionaceae or Pseudoalteromonas. Roseobacter spp. were not lethal to egg yolk sac turbot larvae and in two of three trials, the mortality of larvae decreased (p > 0.001) in treatments where 10(7) cfu/ml Roseobacter sp. strain 27-4 was added, indicating a probiotic potential.

A rare initial manifestation of systemic lupus erythematosus--acute pancreatitis: case report and review of the literature.

BACKGROUND: Acute pancreatitis as the initial manifestation of systemic lupus erythematosus (SLE) has been documented only nine times in the English literature. METHODS: We report the case of a 25-year-old woman patient with fever, abdominal pain and vomiting, elevated levels of pancreatic enzymes, and various other laboratory abnormalities. Further investigation led to a diagnosis of SLE. A literature search, using the key words "systemic lupus erythematosus" and "pancreatitis" was undertaken. RESULTS AND CONCLUSIONS: The treatment of SLE pancreatitis is steroids, which is somewhat controversial because steroids have been implicated in the cause. SLE can involve any organ system. It is important that the family physician, who treats patients as a whole, rules out SLE when a straightforward diagnosis is associated with inexplicable multiple concomitant abnormalities.