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Alopecia areata (AA) is an immune-mediated disease that causes non-scarring hair loss. Autoreactive CD8 T cells are key pathogenic effectors in the skin, and AA has been associated both with atopy and with perturbations in intestinal homeostasis. This study aimed to investigate mechanisms driving AA by characterizing the circulating immunophenotype and faecal microbiome, and by stratifying AA to understand how identified signatures associated with heterogeneous clinical features of the condition. Flow cytometric analyses identified alterations in circulating B cells and CD4 T cells, while 16S sequencing identified changes in alpha and beta diversity in the faecal microbiome in AA. The proportions of transitional and naïve B cells were found to be elevated in AA, particularly in AA samples from individuals with >50% hair loss and those with comorbid atopy, which is commonly associated with extensive hair loss. Although significant changes in circulating CD8 T cells were not observed, we found significant changes in CD4+ populations. In individuals with

Background Treatment with the CD-TREAT solid food diet improves disease activity indices, faecal calprotectin (FCAL) levels and quality of life in adults and children with active Crohn’s disease (CD); particularly in patients who adhere to the diet. Here we describe changes in faecal microbiome parameters during therapy with CD-TREAT and explore these changes against adherence. Methods Children and adult patients with active CD completed an 8-week treatment with CD-TREAT. The levels of FCAL, pH, total sulphide (colorimetry), short chain fatty acids (SCFA), branched chain fatty acids (BCFA) (gas chromatography), total bacterial load (qPCR for total 16S rRNA gene copy number/g) were measured in baseline faecal samples and at four and eight weeks of CD-TREAT. Liquid chromatography mass spectrometry (LC-MS) faecal metabolomics and 16s rRNA sequencing of the faecal microbiome were performed at the same timepoints. Since CD-TREAT is gluten-free, detection of the gluten immunogenic peptide (GIP) in faeces was used as an objective biomarker of treatment adherence. Data are presented as median (IQR). Results Forty patients [17 children, age: 14.0 (11.3-15.1) years; 23 adults, age: 33.9 (27.8-45.9) years] participated. Eighteen (45%) patients had detectable GIP in at least one of the two follow-up timepoints, suggesting incomplete adherence; the remaining 22 (55%) patients had undetectable GIP throughout the treatment course. Baseline FCAL levels decreased significantly in the group of patients with undetectable GIP [mg/kg, baseline: 1,190 (3,611-129); 8 weeks: 534 (92-1,230), p Conclusion We have identified that full adherence with CD-TREAT only occurs in ~55% of recipients, however a significant reduction in calprotectin is seen in those who adhere, and this is associated with microbial and metabolic changes which parallel those seen in successful exclusive enteral nutrition.

Background The fungal community (mycobiome) and immunological responses to specific fungi have been implicated in Crohn’s disease (CD) pathogenesis and its phenotype. There is limited data on profiling the mycobiome in paediatric CD and how it changes during treatment Methods Fungal (ITS2) and bacterial (16S rRNA) microbiome analysis in faecal samples (n=124) from n=34 CD children before, during (30 and 60 days) and after exclusive enteral nutrition (EEN) at food reintroduction (within 60 days of EEN completion), and from 31 healthy controls were profiled. IgA and IgG anti-Saccharomyces cerevisiae antibodies (ASCA) analysis by enzyme-linked immunosorbent assay, in blood, was also carried out for CD patients prior to EEN initiation. Results The global mycobiome composition (β diversity) was different between CD and healthy children (R2=0.050; p=0.007) and presented lower Chao1 richness (mean 24.3 vs 33.0; p=0.005) for the CD cases; 13 fungal operational taxonomic units (OTUs) differed between the two groups. Similar signals were observed for the bacterial microbiome but the difference in global community structure (β diversity) was more profound than the fungal community (R2=0.094; p250 mg/kg). 29 fungal OTUs were significantly different between these two groups in samples taken during food reintroduction, following EEN. Patients who were ASCA positive had a higher abundance of three OTUs of S. cerevisiae. In co-occurrence network analysis, Simplicillium chinense, presented significant more interactions with members of the bacterial community, particularly OTUs which changed during EEN. After participants had returned to their regular diets these microbial effects reversed and community structure moved towards that observed prior to EEN. Conclusion The mycobiome of children with CD present features of dysbiosis similar to the bacterial microbiome and improvement in disease condition during EEN is strongly associated with changes in its composition.

Background Treatment adherence is key to the efficacy of exclusive enteral nutrition (100% EN) in active Crohn’s disease (CD), but there are currently no biomarkers to objectively support this. We explored faecal parameters as putative biomarkers of compliance with 100% EN, and subsequently developed and validated the Glasgow Exclusive enteral Nutrition Index of compliancE (GENIE). Methods Healthy adults replaced all (100% EN) or part (85% EN, 50% EN and 25% EN) of their habitual diet with a polymeric formula (Modulen IBD, Nestle©) for 7 days. Faecal pH, Bristol stool chart score, water content, short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) were measured before (D0) and after (D7) each intervention. Faecal biomarkers and threshold values for group assignments were derived using receiver operating characteristic (ROC) curve analyses and machine learning algorithm to develop the GENIE. The GENIE was validated in 30 children with CD, during 100% EN and 4 weeks after return to normal diet. Results Sixty-one (31 females) adults (mean age [SD]: 25.9 [4.3] years) were recruited. D7 faecal pH and the ratios of BCFAs to either acetate or butyrate performed the best to differentiate between patients on 100% EN from 0.039 and a ratio of IC4 to C2+C4> 0.035 both produced a sensitivity, specificity, and positive predictive value (PPV) of 92%, 83% and 79%, respectively to differentiate between 100% EN vs. all other groups. A faecal pH> 8.0 produced a sensitivity, specificity and PPV of 84%, 86% and 81%, respectively. Findings using machine learning were better than those using ROC curve analysis. Two models were generated; one which includes all faecal metabolites (Laboratory GENIE, L-GENIE), and which produced a sensitivity, specificity and positive predictive value (PPV) of 88%, 94%, and 92%, respectively and a second one (Clinical GENIE, C-GENIE) which considers only faecal pH as the input data and which produced a sensitivity, specificity and PPV of 84%, 86% and 81% (Figure 1). Validation of GENIE models in children with CD found that C-GENIE outperformed L-GENIE, producing a sensitivity, specificity and PPV of 85%, 88% and 88%, respectively (Table 1). Figure 1: Glasgow Exclusive Enteral Nutrition Index of Compliance. Table 1: Results of validation of the GENIE model in children with Crohn’s disease (CD) during treatment with 100% EN and after return to unrestricted diet and compared to the development cohort of healthy adults. Conclusion GENIE can predict adherence to 100% EN in patients with CD in both the clinical and research settings. It may complement conventional dietary assessment and inform clinical decision, especially in patients who are not in remission.

Background & aims: The Remote Malnutrition Application (R-MAPP) was developed during the COVID-19 pandemic to provide support for health care professionals (HCPs) working in the community to complete remote nutritional assessments, and provide practical guidance for nutritional care. The aim of this study was to modify the R-MAPP into a version suitable for children, Pediatric Remote Malnutrition Application (Pedi-R-MAPP), and provide a structured approach to completing a nutrition focused assessment as part of a technology enabled care service (TECS) consultation. ----- Methods: A ten-step process was completed: 1) permission to modify adult R-MAPP, 2) literature search to inform the Pedi-R-MAPP content, 3) Pedi-R-MAPP draft, 4) international survey of HCP practice using TECS, 5) nutrition experts invited to participate in a modified Delphi process, 6) first stakeholder meeting to agree purpose/draft of the tool, 7) round-one online survey, 8) statements with consensus removed from survey, 9) round-two online survey for statements with no consensus and 10) second stakeholder meeting with finalisation of the Pedi-R-MAPP nutrition awareness tool. ----- Results: The international survey completed by 463 HCPs, 55% paediatricians, 38% dietitians, 7% nurses/others. When HCPs were asked to look back over the last 12 months, dietitians (n = 110) reported that 5.7 ± 10.6 out of every 10 appointments were completed in person; compared to paediatricians (n = 182) who reported 7.5 ± 7.0 out of every 10 appointments to be in person (p < 0.0001), with the remainder completed as TECS consultations. Overall, 74 articles were identified and used to develop the Pedi-R-MAPP which included colour-coded advice using a traffic light system; green, amber, red and purple. Eighteen participants agreed to participate in the Delphi consensus and completed both rounds of the modified Delphi survey. Agreement was reached at the first meeting on the purpose and draft sections of the proposed tool. In round-one of the online survey, 86% (n = 89/104) of statements reached consensus, whereas in round-two 12.5% (n = 13/104) of statements reached no consensus. At the second expert meeting, contested statements were discussed until agreement was reached and the Pedi-R-MAPP could be finalised. ----- Conclusion: The Pedi-R-MAPP nutrition awareness tool was developed using a modified Delphi consensus. This tool aims to support the technological transformation fast-tracked by the COVID-19 pandemic by providing a structured approach to completing a remote nutrition focused assessment, as well as identifying the frequency of follow up along with those children who may require in-person assessment.

Background Exclusive enteral nutrition (EEN) and partial enteral nutrition (PEN), replacing at least 50% of the energy intake with formula, remain the only evidence-based dietary therapies in the management of Crohn’s disease (CD). Nonetheless, emerging solid food-based dietary therapies are being researched to offer equally effective, but more palatable alternatives. We assessed the perceptions of adults with CD towards EEN, 50% PEN, and novel dietary therapies within a cross-sectional questionnaire survey. Methods The 26-question anonymous survey with a pre-paid return envelope was mailed to 300 adult patients with CD treated with biologics under the care of the NHS Greater Glasgow & Clyde. A reminder was resent three months later. Responses to open-ended questions regarding concerns about 50% PEN use were analysed independently by two researchers using thematic analysis. Results One-hundred and sixty patients (85/160, 53% female) completed and returned the survey (response rate: 53%). Forty-two percent (67/158) had already followed some form of an exclusion diet, with low spice (32/158, 20%) and low fibre (24/158, 15%) diets being the most popular. Although only a quarter of patients believed that EEN or PEN could help with their CD (42/157, 27%), the majority believed that diet could help (84/157, 54%), with another 13% (21/157) reporting already using diet for CD management. Although only around half of the patients were willing to try EEN (80/157, 51%), the majority were willing to try PEN instead (124/157, 79%) (EEN vs. PEN chi-square: P Conclusion Most adult patients would prefer to follow an exclusion diet meal plan rather than EEN or 50% PEN. However, the majority would try 50% PEN which allows for more flexibility and may be easier to comply with than EEN.

Background Predicting response to treatment with exclusive enteral nutrition (EEN) in paediatric Crohn’s disease (CD) can lead to more personalised, cost-effective, and efficacious therapy. We explored the ability of pre-treatment clinical and multi-omics parameters to predict faecal calprotectin (FCal) levels at EEN completion. Methods In 37 children [median (IQR), 12.4y (10.1, 15.0)] with active CD, disease parameters, dietary intake, 19 inflammatory cytokines, and 92 plasma inflammation-related proteomic markers in plasma, diet-related bacterial metabolites and 1H NMR metabolomics in faeces, as well as the faecal, duodenal, ileal, ascending and descending colon microbiome (16S rRNA sequencing), and dietary intake were measured prior to EEN initiation. Fifteen children responded to EEN (RS) and 12 not (non-RS) using a FCal cut-off Results Disease and host immunological parameters did not predict FCal levels at EEN completion. Responders had lower fibre intake, half the concentration of butyrate, acetate, phenylacetate and higher bacterial richness, in faeces, than non-RS. A model trained with the discriminant duodenal operational taxonomic units (OTUs) demonstrated a sensitivity of 67%, specificity of 90% and positive predictive value of 80% to differentiate RS from non-RS. The predictive ability of the faecal and the microbiomes of other mucosal sites was inferior to that of the duodenum. In multicomponent prediction including all datasets and faecal microbiome, higher levels of phenylacetate and relative abundance of OTU of Bacteroides, were predictive of non-RS with a sensitivity of 73%, specificity of 81% and positive predictive value of 73%. Replacing the faecal with the duodenal microbiome in a subset of participants (n=14), produced a model with 100% accuracy to predict RS from non-RS. The single most important variable in this model was a Lachnospira OTU which was absent in all RS but highly abundant in non-RS. Conclusion We identified pre-treatment microbial signals and diet-related metabolites which may comprise targets for pre-treatment optimisation and personalised nutritional therapy in CD.

Background Biochemical deficiencies of iron, B12, vitamin D, vitamin K, folic acid, selenium and zinc are common in patients with Inflammatory Bowel Disease (IBD) and some micronutrient deficiencies have been associated with adverse disease outcomes. This study describes the micronutrient status of a cohort of patients on biologic therapy for IBD and explores the relationship with disease activity. Methods Adult patients with IBD on biologic therapy attending the nurse specialist clinic had 16 serum micronutrients measured alongside routine biochemical screening for disease activity. 12 months of follow up data was collected using electronic patient records. Faecal calprotectin (FCP), albumin and CRP were measured at baseline - patients in whom these biomarkers were within normal range (i.e CRP 35g/L and FCP Relationships between micronutrient status and time to disease relapse were explored. Results 216 patients (42% female, median age 42, IQR: 30–57) were included. 128 patients had Crohn’s disease (CD). 97 patients were in biochemical remission at enrolment. 12.9% of the total cohort were zinc (Zn) deficient and 6.5% were selenium (Se) deficient. Deficiencies of folate, vitamin C, vitamin B12, vitamin B6 and vitamin D were also prevalent within the cohort. Se deficiency was associated with high CRP (p=.001), low albumin (p=.022), and raised FCP (p=.002) at baseline. Zn deficiency was associated with high CRP (p Patients with low Zn or low Se levels at baseline were significantly more likely to relapse (p=.007 and p=.019 respectively). In subtype analysis, patients with CD and Zn deficiency were significantly more likely to relapse (p=.003) but this was not the case for UC patients. Patients with UC and Se deficiency were significantly more likely to relapse (p=.001) whereas those with CD were not. Conclusion Zn and Se biochemical deficiencies are common in our cohort of IBD patients on biologic therapy and are predictive of subsequent disease relapse. Whether these signals are causal or a secondary effect of disease activity needs to be explored in future intervention studies.

Background Infliximab (IFX) is increasingly used in the management of moderate to severe ulcerative colitis (UC) and as a ‘rescue’ treatment for acute severe UC (ASUC) but primary non response (PNR) and colectomy rates remain significant. Reasons for IFX treatment failure in ASUC are multifactorial but immunogenicity and faecal loss of drug are thought to be important factors. Emerging evidence suggests accelerated ‘rescue’ IFX dosing may be more effective. The aim of this work was to establish if a relationship exists between faecal IFX levels, disease activity, and clinical outcomes early in IFX treatment. Methods Patients with UC were prospectively recruited following initiation of IFX and designated as ASUC or non-ASUC based on Truelove and Witt’s criteria. Stool and serum were collected on days, 0, 7, 14, 28 and, 42 after initiation of IFX. Additional samples on days, 1–5 after IFX were obtained from inpatients. Albumin and CRP results were extracted from electronic patient records. Faecal calprotectin (FC) was measured using ELISA (CALPROLAB). Faecal IFX within the first, 2 weeks of treatment was analysed using a Promonitor-IFX-1DV ELISA assay, performed on the Triturus ELISA instrument. R studio was used to calculate areas under the curves of the time series. Spearman’s rank correlation test was used for correlation analysis. Results 20 patients were recruited, 12 with ASUC. Faecal IFX correlated strongly with FC (ρ=0.793;p Conclusion In this small cohort, faecal loss of IFX was associated with increased markers of systemic and luminal inflammation. Its role as a biomarker for disease severity, treatment response and clinical outcomes warrants further investigation. The rapid fall but early rebound rise in FC may support the need for earlier accelerated dosing in ASUC. However, larger studies are needed to establish the optimal early IFX regime to improve clinical outcomes. References Papamichael et al. Aliment Pharmacol Ther, 2018;47:478–484. Hindryckx et al. Aliment Pharmacol Ther., 2017 March;45(5):, 617–630 Brandse et al. Gastroenterology., 2015 Aug;149(2):350–5

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) is an established induction treatment for active Crohn’s disease (CD) with a proposed mechanism of action involving the gut microbiome. We have previously shown that CD-TREAT diet, a food-based diet with similar dietary profile to EEN, improves rat ileitis and replicates the effect of EEN on the gut microbiome of healthy volunteers and animal models. Here, we test the efficacy of CD-TREAT diet to induce clinical remission in active CD. Methods This is an open-label study in children (wPCDAI≥12.5) and adults (HBI≥5) with active CD. Primary outcome was clinical response (wPCDAI fall≥17.5; HBI fall≥3) or clinical remission (wPCDAI< 12.5; HBI Results 25 children, [age, 14.4 (12.5,15.7) years] and 32 adults, [age, 32.6 (24.2,43.9) years] were treated. 7 (12%) failed treatment and n=10 (18%) dropped out during the first 2 weeks of treatment due to palatability issues. In patients who completed 8 weeks of CD-TREAT course (n=40), 85% and 78% achieved clinical response and remission, respectively. CD-TREAT diet improved QoL in children [IMPACT-III score, baseline: 136 (122,143) vs 8weeks: 148 (133,153), p50% FC reduction. Median FC levels decreased significantly? in the group of patients (n=22) who had undetectable GIP at 4 or 8 weeks [mg/kg FC, baseline: 1190 (361,1129); 8weeks: 534 (92,1230), p Conclusion CD-TREAT diet improved disease activity indices and QoL in the majority of patients who completed treatment and decreased FC in those who were most likely to be compliant. Future RCT should aim to compare CD-TREAT with other induction treatments and improve meal variety and palatability to improve compliance and reduce drop-out rates.

Background Findings from five randomised trials using faecal microbiota transplantation (FMT) in adults with ulcerative colitis (UC) demonstrate therapeutic potential. The optimum methodology for administration of FMT is unclear. We describe a prospective, three centre, open-label randomised trial (STOP-Colitis pilot) that compared tolerability and efficacy of nasogastric (NG) versus colonic (COLON) routes of administration and identified potentially important host microbial interactions. Methods Adult participants with active UC (partial Mayo score of ≥4 and ≤8) were randomised for administration of, 8 infusions of FMT over an, 8 week period either via the naso-gastric (NG) or colonic (COLON) route. Each patient was matched to a single FMT donor. Clinical response was defined as ≥3 point and ≥30% reduction in full Mayo score at week, 8 compared to baseline. Changes in faecal gut microbial diversity (Shannon’s diversity) and composition before/after FMT were analysed with, 16S rRNA sequencing. Correlation between datasets was evaluated with Kendall’s Tau coefficient. Results Sixteen patients were randomised to NG;, 14 to COLON FMT. Seven participants in the NG and, 2 in the COLON arm withdrew before completion. Clinical response was achieved in, 9/12 [75%] for COLON vs, 2/8 [25%] for NG)., 12/14 (86%) COLON participants were protocol-adherent compared with, 8/16 (50%) for NG. For the COLON patients (N=8) an increase in alpha diversity was observed (P=0.01). For those patients that responded to FMT overall (N=9) there was a significant increase in alpha diversity (P Conclusion This pilot study suggests that in participants with active UC, FMT delivered via the colonic route appears to be better tolerated than via NG with a greater efficacy signal. There are signals linking gut microbial diversity and taxa belonging to Clostridia (short chain fatty acid producers) with clinical response, calprotectin and a shift towards an immunoregulatory phenotype.

Background It is yet unclear whether suboptimal response to exclusive enteral nutrition (EEN), in some children with Crohn’s disease (CD), is explained by poor compliance. All proprietary feeds used for EEN are gluten-free; hence patients’ compliance to EEN could be determined by detecting gluten immunogenic peptide (GIP), a biomarker of gluten intake, in faeces. Methods The concentration of GIP was measured in the faeces of, 45 children (3–17 years) with CD prior to and during (33 &, 54 days) treatment with EEN. Associations with GIP and faecal calprotectin (FCAL) levels were explored at, 33 and, 54 days of EEN. Results GIP was present in, 37 of the, 40 (93%) patients who provided stool samples prior to starting EEN, indicating typical gluten consumption in CD patients. In patients with undetectable GIP at both, 33 and, 54 days of EEN, FCAL significantly decreased from baseline (mean decrease, 33 days: -743mg/kg, 54 days: -1043mg/kg, p Conclusion Poor response to EEN might be explained at least in part by diminished compliance and dietary transgressions. Faecal GIP might be useful as a proxy biomarker of EEN compliance.

Background It has been suggested that the gut microbiome of patients with inflammatory bowel disease (IBD) is unable to ferment dietary fibre. This project explored the in vitro effect of fibre fermentation on production of short chain fatty acids (SCFA) and on microbiome composition. Methods Faecal samples were collected from 40 adults (>16 y) with IBD (n=20 with Crohn’s disease and n=20 with Ulcerative colitis) in clinical remission and 20 healthy controls (HC). In vitro batch culture fermentations were carried out using as substrates maize starch, apple pectin, raftilose, wheat bran, α cellulose and a mixture of these 5 fibres. SCFA concentration (umol/g) was quantified with gas chromatography and microbiome was profiled with 16S rRNA sequencing. Results Fibre fermentation did not correct the baseline microbial dysbiosis or lower diversity seen in either CD or UC. For all fibres, up to 51% of baseline ASVs or genera changed in abundance in HC. In patients with IBD, fermentation of fibre substrates had no effect on species or genera abundance. Production of SCFA varied among the different fibre substrates but this was not different between the two IBD groups and compared to HC after either 5 or 24 hour fermentation. Conclusion Despite extensive microbial dysbiosis, patients with IBD have a similar capacity to ferment fibre and release SCFA as HC. Fibre supplementation alone may be unlikely to restore to a healthy status the compositional shifts characteristic of the IBD microbiome.

Background Exclusive enteral nutrition (EEN) is an established treatment for the induction of clinical remission in children with active Crohn’s disease (CD). However, the benefit of partial enteral nutrition (PEN), in which only some diet is replaced with enteral nutrition, is not well-documented for the management of CD. This review explored the effectiveness of PEN as sole or adjunctive induction and maintenance therapy in patients with CD. Methods The protocol for this review was registered on PROSPERO (https://www.crd.york.ac.uk/prospero/ protocol ID: CRD42021239325). Literature search was conducted using PubMed, Ovid Embase, Cochrane Controlled Register of Trials and Cumulative Index to Nursing and Allied Health Literature electronic bibliographic databases. Eligible study designs included: randomised control trials (RCTs), prospective, retrospective, and case control studies. Level of evidence was assessed with CASP tools with an emphasis on study design, and assessment of compliance and objective disease activity biomarkers. Two researchers evaluated each paper separately and when needed, consensus was resolved by a third. Results 56 articles met the inclusion criteria, grouped under the following 6 distinct areas for PEN use in CD: 1) induction treatment; 2) maintenance treatment; 3) prevention of post-operative recurrence; 4) prevention of loss of response (LOR) to anti-TNFα therapies; 5) nutritional rehabilitation; 6) improvement of quality of life (QOL). Low-quality evidence suggests PEN may improve disease activity in patients with active CD; treatment efficacy was observed to be better in studies using higher proportions of energy intake from PEN. Good quality evidence suggests PEN combined with exclusion diets may be effective in active CD. However, most available studies originated from a single research group, and the additional benefits of exclusion diets over PEN are unclear, particularly as most studies used either high PEN volumes (>75% of energy requirements), or EEN prior to PEN initiation. Good quality evidence shows that PEN at high volumes (≥35–50%) may prolong medically or surgically induced remission and improve the nutritional status of patients with malnutrition or growth delay. Low-quality evidence suggests that PEN may improve response and remission rates to infliximab therapy in CD. Three retrospective studies found that concomitant PEN with anti-TNFα therapies could prevent LOR. Some evidence indicates that PEN is associated with better QOL in patients with active disease or in remission. Conclusion PEN may have a beneficial role in various aspects of CD management; however, more robust data including RCTs are needed before specific recommendations can be made.

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.

Background The incidence of inflammatory bowel disease [IBD] is rising worldwide and no cure is available. Many patients require surgery and they often present with nutritional deficiencies. Although randomised controlled trials of dietary therapy are lacking, expert IBD centres have long-established interdisciplinary care, including tailored nutritional therapy, to optimise clinical outcomes and resource utilisation. This topical review aims to share expertise and offers current practice recommendations to optimise outcomes of IBD patients who undergo surgery. Methods A consensus expert panel consisting of dietitians, surgeons, and gastroenterologists, convened by the European Crohn’s and Colitis Organisation, performed a systematic literature review. Nutritional evaluation and dietary needs, perioperative optimisation, surgical complications, long-term needs, and special situations were critically appraised. Statements were developed using a Delphi methodology incorporating three successive rounds. Current practice positions were set when ≥80% of participants agreed on a recommendation. Results A total of 26 current practice positions were formulated which address the needs of IBD patients perioperatively and in the long term following surgery. Routine screening, perioperative optimisation by oral, enteral, or parenteral nutrition, dietary fibre, and supplements were reviewed. IBD-specific situations, including management of patients with a restorative proctocolectomy, an ostomy, strictures, or short-bowel syndrome, were addressed. Conclusion Perioperative dietary therapy improves the outcomes of IBD patients who undergo a surgical procedure. This topical review shares interdisciplinary expertise and provides guidance to optimise the outcomes of patients with Crohn’s disease and ulcerative colitis. taking advantage of contemporary nutrition science.

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

Obesity is the most common cause of metabolic complications and poor quality of life in Prader-Willi syndrome (PWS). Hyperphagia and obesity develop after an initial phase of poor feeding and failure to thrive. Several mechanisms for the aetiology of obesity in PWS are proposed, which include disruption in hypothalamic pathways of satiety control resulting in hyperphagia, aberration in hormones regulating food intake, reduced energy expenditure because of hypotonia and altered behaviour with features of autism spectrum disorder. Profound muscular hypotonia prevents PWS patients from becoming physically active, causing reduced muscle movements and hence reduced energy expenditure. In a quest for the aetiology of obesity, recent evidence has focused on several appetite-regulating hormones, growth hormone, thyroid hormones and plasma adipocytokines. However, despite advancement in understanding of the genetic basis of PWS, there are contradictory data on the role of satiety hormones in hyperphagia and data regarding dietary intake are limited. Mechanistic studies on the aetiology of obesity and its relationship with disease pathogenesis in PWS are required. . In this review, we focused on the available evidence regarding mechanisms of obesity and potential new areas that could be explored to help unravel obesity pathogenesis in PWS.

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.

Disease-associated undernutrition of all types is very common in paediatric inflammatory bowel disease (IBD). Recent weight loss remains one of the triad of clinical manifestations and a cornerstone for the diagnosis of Crohn's disease (CD), although significantly fewer patients now present as being underweight. Recent evidence suggests that the introduction of medical treatment will quickly restore body weight, although this does not reflect concomitant changes in body composition. CD children present with features of nutritional cachexia with normal fat stores but depleted lean mass. Poor bone health, delayed puberty and growth failure are additional features that further complicate clinical management. Suboptimal nutritional intake is a main determinant of undernutrition, although activation of the immune system and secretion of pro-inflammatory cytokines exert additional independent effects. Biochemically low concentrations of plasma micronutrients are commonly reported in IBD patients, although their interpretation is difficult in the presence of an acute phase response and other indices of body stores adequacy are needed. Anaemia is a common extraintestinal manifestation of the IBD child. Iron-deficient anaemia is the predominant type, with anaemia of chronic disease second. Decreased dietary intake, as a result of decreased appetite and food aversion, is the major cause of undernutrition in paediatric IBD. Altered energy and nutrient requirements, malabsorption and increased gastrointestinal losses are additional factors, although their contribution to undernutrition in paediatric CD needs to be studied further.

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.

Objectives: To compare aortoenteric fistula (AEF) outcome after endovascular (EV-AEFR) or open repair (O-AEFR). Design: Multicentre retrospective comparative study. Materials/Methods: 25 patients with AEF (24 secondary, 23 males, median age 75 years) after aortic surgery (median four years). Preoperative sepsis was evident in 19 cases. Eight patients were managed with EV-AEFR and 17 with O-AEFR. Results: The two groups were comparable in preoperative characteristics. In-hospital mortality after EV-AEFR was lower compared to O-AEFR (0% and 35%, respectively, p = 0.13). Similarly, morbidity after EV-AEFR was lower compared to O-AEFR (25% and 77%, respectively, p = 0.028). There was a trend for worse recurrence-free, sepsis-free, re-operation-free and AEF-related death-free rates after EV-AEFR, while the early survival advantage of EV-AEFR was lost after two years and the overall long-term survival rates (perioperative mortality included) of the two groups were similar. Preoperative sepsis had no effect on recurrence and sepsis-free rates (p = 0.94 and p = 0.92, respectively), but it was associated with worse two year overall survival (24% vs 50%, p = 0.32). On multivariate analysis, the number of symptoms (two vs one) at presentation was the single predictor of worse re-operation rates, AEF-related and overall survival. Conclusions: EV-AEFR was associated with no postoperative mortality in this study and can achieve satisfactory short and long-term results, comparable to O-AEFR. Further trials should focus on the role of EV-AEFR in patients at high risk for O-AEFR, due to shock or co-morbidities, or as a bridging procedure. © 2010 European Society for Vascular Surgery.

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.