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Introduction Treatment with exclusive enteral nutrition (EEN) offers a nutritional therapy paradigm in Crohn’s disease, with the extensive modulation of gut microbiome being its proposed mechanism of action(1). Recent studies propose variable clinical efficacy for 85% EN (Cheat EN/CEN), 50% EN (Partial EN/PEN) and 20% EN (maintenance EN/MEN), and a dose-dependent effect of EN use in CD(2–4). Therefore, this study aims to investigate the dose-dependent effect of 100%, 85%, 50%, and 20% EN on faecal microbial metabolites; and to investigate if this effect can be used as a compliance marker for EEN. Methods Healthy adults followed EEN, CEN, PEN or MEN diet for 7 days. Fresh faecal samples were collected before and after each dietary intervention. Dietary assessment was performed throughout the intervention using estimated weight food diaries. Faecal pH, Bristol Stool Chart Score (BSCS), short chain fatty acids and hydrogen sulphide were measured. Results 122 faecal samples were collected from 61 subjects. The Mean(SEM) EN intake for the 4 groups was EEN:100(0), CEN:86(0.5), PEN:50(0.4), MEN:20(0.2)% of total energy intake. The baseline levels of all faecal sample measures were no different between the 4 groups. Faecal propionate and BSCS significantly decreased only during EEN (all p≤0.03). Faecal pH significantly increased during EEN, CEN and PEN (all p Conclusions EEN and CEN extensively modulate faecal microbial metabolites. PEN induces variable effects and further analysis should investigate if this variation reflects differences in the non-EN food intake of the participants (50%). MEN had no effect on faecal microbial metabolites. Further analysis including high-throughput deep sequencing techniques will provide additional information about the dose-dependent effect of EN regimen on gut microbiome composition. 1) Quince, Am J Gastroenterol 110, 1718–1729; 2) Logan, APT 50, 664–674, 2019; 3) Gupta, IBD 19, 1374–1378, 2013; 4) Lee, IBD 21, 1786–1793, 2015

Background Exclusive enteral nutrition (EEN) is the recommended first line treatment for active paediatric Crohn’s disease (CD). The mechanism of action and immunological effects of EEN remain unclear. This study compared circulating inflammatory proteins of patients with CD and ulcerative colitis (UC) with non-inflammatory bowel disease (non-IBD) controls and explored the effect of EEN in children with active CD. Methods Patients with CD were treated with EEN for 8 weeks, with plasma samples collected prior to EEN start and upon EEN completion. Levels of 92 inflammatory proteins were quantified using Olink Inflammation panel. Paired faecal samples were collected to measure faecal calprotectin (FC) levels by ELISA. Patients in which FC decreased >50% during EEN were classed as FC responders; whereas patients who had a Results 84 patients were recruited (CD:54, UC:11, non-IBD:19). Paired plasma samples were collected from 18 patients with CD receiving EEN. Of these 18 patients, 72% achieved clinical remission by the end of EEN (wPCDAI Prior to EEN start, 29 proteins were significantly different between patients with CD compared to non-IBD; and 25 proteins were significantly different between UC and non-IBD, Fig 1. EEN lead to the significant alteration of 23 proteins. This included 5 proteins, CCL23, CXCL10, IL6, IL24, and MMP-1 which were higher in patients with CD prior to EEN start compared to non-IBD, Fig 2. In patients who achieved clinical remission during EEN, 22 proteins significantly changed from their EEN start levels by the end of EEN, Fig 3. FC responders had a similar pattern of protein changes, in which 22 proteins changed significantly during EEN, Fig 4. 16/22 (72%) of the proteins that changed significantly in the FC responder group during EEN, also changed during EEN in patients who entered clinical remission including significant reductions in several innate immune proteins such as IL-6 and IL-18. Patients who did not achieve clinical remission did not have significant reductions in these proteins. Despite being higher in patients with CD prior to treatment compared to non-IBD, the level of 17 proteins, including IL17a and oncostatin M, did not change in FC responders during EEN. Conclusion EEN leads to alteration of multiple inflammatory proteins, in keeping with a reduction in innate immune pro-inflammatory activity and improvement in clinical response, although some inflammatory proteins remain elevated. Figure 1: Venn diagram of proteins significantly different Figure 2: Effect of EEN on protein levels Figure 3: Effect of EEN on protein levels, stratified based on clinical response during EEN Figure 4: Effect of EEN on protein levels, stratified based on FC response

Background Induction of clinical remission with exclusive enteral nutrition (EEN), has been associated with accompanying changes in the concentration of short chain fatty acids (SCFA) (a biomarker of fibre fermentation) in faeces of children with Crohn’s disease (CD) 1. Here, we assessed the fibre fermentative capacity of the gut microbiota of children with active CD in vitro, before, during and after EEN and compared with healthy children. Methods 44 faecal samples from 14 children (female, n=7, age, median [Q1, Q3]: 14.1 [11.1, 15.1] years) with active CD were collected before, during (4 weeks) and at the end of EEN (8 weeks) and after food reintroduction (median [Q1, Q3]: 21 [16, 31] days post-EEN). All children had achieved clinical remission at the end of EEN (weighted Paediatric Crohn’s Disease Activity Index Results Compared to healthy children, the total production of SCFA was significantly lower in children with CD, for all 4 fibre substrates, and regardless of the study timepoint (Figure 1). Net production of SCFA remained unchanged during EEN and at food reintroduction, and for all fibre substrates (Figure 1). No significant association with levels of faecal calprotectin was observed at any of the timepoints. Acetate production was significantly lower in children with CD compared to healthy children for all fibre substrates except for resistant maize starch (Figure 1). Likewise, except for pectin, production of butyrate was significantly lower in children with CD than healthy controls (Figure 1). Production of propionate did not significantly differ between any of the groups. Legend: Production of SCFA after 24-hour in vitro fermentation of faecal samples from CD and healthy children. Asterisks indicate significant differences. A: before EEN, B: 4-week EEN, C: End of EEN, D: Food reintroduction, HC: Healthy children Conclusion Fibre fermentative capacity is independent of disease activity in patients with CD and remains lower compared to healthy controls. It might be unlikely that the mechanism of action of EEN is mediated by modulation of fibre fermenting bacteria. Reference 1. Gerasimidis K, Bertz M, Hanske L, Junick J, Biskou O, Aguilera M, et al. Decline in presumptively protective gut bacterial species and metabolites are paradoxically associated with disease improvement in pediatric Crohn’s disease during enteral nutrition. Inflamm Bowel Dis. 2014;20(5):861–71.

Background Exclusive enteral nutrition (EEN) ameliorates gut inflammation in children with Crohn’s disease (CD). We have previously described the rapid rise in faecal calprotectin levels (FC) when children with CD return to their habitual diet after EEN treatment (1). We performed dietary assessment and measured biomarkers of food consumption in faeces of children with CD during early food reintroduction. Methods A composite outcome of clinical remission post EEN (weighted Paediatric Crohn’s Disease Activity Index 500 mg/kg / >35%) was used to define the patient group. All patients completed 3-day estimated weight food diaries and provided a faecal sample. Patients were divided equally for statistical analysis purposes in two groups; above (Group 1) and below (Group 2) the median FC concentration at food reintroduction. Nutrient analysis was performed with WinDiets. Short-chain fatty acids, the gluten immunogenic peptide (GIP) and starch were measured in stool, as proxy of fibre, gluten and malabsorbed starch, respectively. Food groups were assigned using the National Diet and Nutrition Survey approach and statistics employing taxonomy were utilised in the food group analysis. All data are displayed using medians (Q1, Q3). Results Fourteen children provided an FC sample within 21 (15, 51) days post EEN. Patients were of similar age, weight and height (p = 0.4, p = 0.37, p = 0.79). Total energy intake did not differ between the groups (p = 0.37). Patients in Group 1 consumed more fibre than Group 2 [12.1 g (11.3, 19.9) vs. 9.9 g (7.6, 12.1), p = 0.04]. Protein and phosphorus intakes, expressed as a percentage of reference nutrient intakes, were also higher in Group 1 than Group 2 [protein (%): 262 (195, 291) vs. 211 (88, 215), p = 0.02], [phosphorus (%): 241 (171, 290) vs. 177 (131, 1901), p = 0.04]. Butyrate and valerate levels were higher in Group 1 than Group 2 [butyrate: 62.5 (41.8, 114) vs. 34.1 (29.2, 49.6), p = 0.02; valerate: 13.7 (9.3, 17.9) vs. 4.5 (2.3, 8.1), p < 0.01. There were no differences in GIP and faecal starch levels between the two groups. Red and processed meat intake was higher in Group 1 than Group 2 [151 g (66.7, 190) vs. 63.3 g (21.7, 67), p = 0.02)]. Cereals intake was non-significantly higher in Group 1 [389 (207, 405) vs. 231 (141, 279), p = 0.08]. Overall diet diversity did not differ between the two groups (p = 0.47). Conclusion The current analysis suggests that fibre, protein, phosphorus and red and processed meat may be associated with recurrence of colonic inflammation in children with CD during early food reintroduction. These findings should be confirmed in larger studies. Reference

Background Exclusive enteral nutrition (EEN) is an effective treatment of Crohn’s disease (CD). We hypothesise that food ingredients which are included in EEN formulas are less likely to initiate a disease flare and that their dietary elimination is not essential for disease amelioration. Methods We performed a compositional analysis of EEN formulas with evidence of clinical efficacy for the induction of remission in active CD. Macronutrient content was compared against the dietary reference values (DRVs), the UK National Diet and Nutrition Survey (NDNS) and children with CD. Food additives included with EEN formulas were cross-referenced against the FAO/WHO database. Results Sixty-one formulas were identified with variable composition [carbohydrates (23–89%), protein (8–30%), fat (0–50%)], Figure 1. Modified starches (e.g. maltodextrin), milk protein and vegetable/plant oils were the commonest sources of carbohydrate, protein and fat, respectively, Figure 2. The n-6:n-3 fatty acid ratio varied from 0.3 to 46.5. Fifty-six unique food additives were identified contained within EEN formulas (median per formula: 11), Figure 3. All formulas were lactose, gluten free. Eighty per cent lacked fibre. The five commonest food additive functional classes were emulsifiers, stabilisers, antioxidants, acidity regulators, and thickeners. Food additives, implicated in CD aetiology, were present in formulas [modified starches (100%), carrageenan (23%), carboxymethyl cellulose (14%) and polysorbate 80 (5%)]. EEN formulas derived 7.9% less energy from saturated fat than participants from the NDNS (p = 0.001). CD children consumed more sugars, total/saturated fat than the EEN content. Conclusion We provide a list of food ingredients which are unlikely, in the amount provided within EEN, to trigger CD activity. Current perceptions about the role of these ingredients in CD management are challenged.

No abstract available.

Introduction The extensive modulation of the gut microbiome in Crohn’s disease (CD) children treated with exclusive enteral nutrition (EEN) offers clues about EEN’s potential mode of action; but also on the development of novel therapies through dietary manipulation of the gut microbiota. This proof of concept study compared the effect of a novel ‘ordinary’ food diet (CD-TREAT diet) and EEN on A)healthy human and B)colitic rat gut microbiota. Method A)Healthy adults followed two experimental diets for 7 days with a 15 day wash out period in between; EEN and CD-TREAT, an ”ordinary” food diet with similar nutrient and food ingredient composition to EEN. Faecal and urine samples were collected before and after each intervention and 16srRNA sequencing, untargeted faecal and urine metabolomics were performed; B)10-month-old HLA-B27 and HLA-B7 trangenic rats received EEN, CD-TREAT or regular rat chow for 4 weeks. Faeces were collected before, during and post treatment and gut contents/tissue at sacrifice. Disease activity was quantified by blinded histological scores. Gut bacterial metabolic activity was measured by faecal short chain fatty acids (SCFA) quantification. Results A)100 faecal and urine samples were collected from 25 healthy adults. Gut bacterial community structure significantly changed after both EEN (R2=0.15,p=0.001) and CD-TREAT (R2=0.05,p=0.003) and shifted towards the same direction. EEN’s and CD-TREAT’s impact on 3%OTU community structures was strongly correlated (R2=0.38,p Conclusion We have developed an ”EEN composition-like” food diet which induces similar gut microbiome changes with EEN. These proof of concept data support a subsequent pilot trial in patients with active CD. Disclosure of Interest None Declared

To determine the validity of estimation of body fatness by dual-energy x-ray absorptiometry (DXA) and foot-foot bio-electrical impedance (BIA).In 176, 11-12-year-olds (84 boys; 92 girls) body fatness was measured using total body water (TBW), derived from deuterium oxide dilution space. Body fatness was also estimated from DXA and BIA. Methods were compared by regression and by Bland-Altman analysis using TBW measures as the reference.In boys, mean fat mass from TBW was 9.8 kg (standard deviation, SD=6.1); bias by DXA estimated fat mass was +0.9 kg (limits of agreement -2.2 to +4.1) and bias for BIA was -5.2 kg (limits of agreement +0.5 to -10.8). In boys, regression analysis indicated significant differences in slope (p0.001) for DXA, and both slope (p0.001) and intercept (p0.001) for BIA. In girls, mean fat mass from TBW was 12.1 kg (SD 7.7); bias for DXA was +1.2 kg (limits of agreement -1.9 to +5.1) and bias for BIA was -0.2 kg (limits of agreement -5.4 to +5.1). In girls, regression analysis indicated significant differences for slope and intercept (p0.001 in all cases) for both DXA and BIA.Errors in estimation of fat mass using BIA and DXA can be very large, and the direction of error can differ between the sexes.

Background: An accurate indication of the changing incidence of pediatric inflammatory bowel disease (PIBD) within a population is useful in understanding concurrent etiological factors. We aimed to compare the current incidence and other demographic attributes of PIBD in the Scottish population to previous data. Methods: A national cohort of prospectively and retrospectively acquired incident cases of PIBD diagnosed less than 16 years old in pediatric services in Scotland was captured for the period 2003-2008; historical Scottish data were used for comparison (1990-1995). Age/sex-adjusted incidences were calculated and statistical comparisons made using Poisson regression. Results: During the 2003-2008 study period 436 patients were diagnosed with PIBD in Scotland, giving an adjusted incidence of 7.82/100,000/year. The incidence of Crohn's disease (CD) was 4.75/100,000/year, ulcerative colitis (UC) 2.06/100,000/year, and inflammatory bowel disease-unclassified (IBDU) 1.01/100,000/year. Compared with data from 1990-1995 when 260 IBD patients were diagnosed, significant rises in the incidence of IBD (from 4.45/100,000/year, P < 0.0001), CD (from 2.86/100,000/year, P < 0.0001), and UC (from 1.59/100,000/year, P = 0.023) were seen. There was also a significant reduction in the median age at IBD diagnosis from 12.7 years to 11.9 years between the periods (P = 0.003), with a continued male preponderance. Conclusions: The number of Scottish children diagnosed with IBD continues to rise, with a statistically significant 76% increase since the mid-1990s. Furthermore, PIBD is now being diagnosed at a younger age. The reason for this continued rise is not yet clear; however, new hypotheses regarding disease pathogenesis and other population trends may provide further insights in future years. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Introduction EEN is an effective 1st line treatment for active paediatric Crohn9s disease (CD). We explored the short & long term effects of EEN including anthropometric parameters and evaluated factors that predicted subsequent disease outcomes. Methods A retrospective case note review in newly diagnosed CD ( Results 110 patients were included (Males 68; Median age: 11.2 years). At diagnosis 34% were thin (BMI ≤−2SD), 1% obese (BMI ≥2SD), 10% had short stature (height ≤ −2SD) and 25% were underweight (weight ≤−2SD). By 4 weeks of EEN weight and BMI z-score increased significantly (−1.1 cf. −0.6 and −1.3 cf. −0.4 respectively, p 9 ): 525±147 vs 471±165; all p 44 patients completed a 2 nd course of EEN; median weight gain improved but was less than the initial course (3.3 vs 5.1 kg, p Conclusion Anthropometry improves with EEN but the change is smaller in the second half of the initial course or in secondary courses. Weight gain is not a predictor of time to relapse or anthropometry at follow-up to 2 years. Systemic inflammatory markers improve during the 1 st 4 weeks of treatment with little improvement at the second half.