An update on dietary therapies in paediatric Crohn's disease.

PURPOSE OF REVIEW: This article provides a literature update on original articles published in the past 18 months (May 2022-November 2023) in the dietary management of paediatric Crohn's disease. RECENT FINDINGS: There is more data to support the use of exclusive enteral nutrition in the management of active Crohn's disease in children. Several food-based dietary therapies have been proposed for the management of Crohn's disease. There is an interest in precision nutritional therapy in Crohn's disease, but current data are scarce. SUMMARY: Exclusive enteral nutrition is an effective treatment for paediatric Crohn's disease. Predictors of response to exclusive enteral nutrition include mild disease phenotype and ileal disease involvement, although data remain inconclusive. Adherence to exclusive enteral nutrition is cornerstone to its efficacy. Treatment with exclusive enteral nutrition modifies the gut microbiome, modulates bile acid metabolism and has significant effects on host immune responses. More studies are expected in which drugs need to be combined with dietary therapies and microbial therapeutics. The efficacy of Crohn's disease exclusion diet coupled with partial enteral nutrition is supported by independent studies, but tolerance remains an issue, particularly for long-term disease management. More research is anticipated in precision nutritional therapy in paediatric Crohn's disease, but currently no recommendations can be made.

Exclusive enteral nutrition impacts peripheral blood mononuclear cell profile of children with Crohn's disease.

The immunological effects of exclusive enteral nutrition (EEN) in the treatment of active Crohn's disease (CD) are yet to be unveiled. The present study investigated changes in peripheral blood mononuclear cell profiles in children with active CD following 8-week treatment with EEN. In nine children, EEN significantly decreased the number and frequency of circulating effector memory CD8+ T cells re-expressing CD45RA, with corresponding increases observed in the frequency of circulating central and effector memory CD8+ T cells. These signals were conserved when looking at a subgroup of patients who achieved remission, and another who demonstrated the highest level of compliance to EEN. We speculate that the increases in circulating central and effector memory CD8+ T cells may be related to the extensive microbiome-modifying effects of EEN dampening immune response within the gastrointestinal tract.

Clinical performance of the infant nutrition early warning score in routine practice across four international clinical settings in Europe: A study by the ESPGHAN special interest group in clinical malnutrition.

There is a scarcity of nutritional screening tools for use in infants (<1 year). The infant Nutrition Early Warning Score (iNEWS) has been developed to identify infants who need further dietetic review. We introduced the iNEWS into clinical practice and evaluated its performance in Scotland, Belgium, Athens and Bulgaria. Of the 352 infants screened, 72 (20%) were placed in the high iNEWS category, and of these, 70 (97%) were reviewed by a hospital dietitian. iNEWS produced a true positive rate of 80% which increased to 96% after accounting for anticipated misclassified cases due to prematurity. In Belgium, false positive screens had a shorter length of stay (p = 0.014). Otherwise, misclassification was not related to a specific iNEWS component. This study corroborates previous research, underscoring the validity of iNEWS as a dietetic referral tool and demonstrating that it can be integrated into "real-world" clinical practice across international settings with diverse healthcare resources.

Anthropometric assessment: ESPGHAN quality of care survey from paediatric hospitals in 28 European countries.

OBJECTIVES: Assessment of anthropometric data is essential for paediatric healthcare. We surveyed the implementation of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) evidence-based guidelines and practical recommendations on nutritional care, particularly regarding anthropometric measurements. METHODS: Paediatric hospitals from 28 European countries provided pseudonymized data through online questionnaires on hospital characteristics and their standards of nutritional care. Practical tasks assessed an unbiased collection and reporting of anthropometric measurements in random patients' files and discharge letters. RESULTS: Of 114 hospitals (67% academic), 9% have no nutritionist/dietitian available, 18% do not provide standard policy to assess weight and height and 15% lack training for nursing staff for accurate performance. A wall-mounted stadiometer to measure standing height and equipment for sitting weight is unavailable in 9% and 32%, respectively. Infant length is measured by one instead of two healthcare professionals and with a tape instead of a rigid length measuring board in 58% and 15% of hospitals, respectively. The practical tasks reviewed 1414 random patients, thereof 446 younger than 2 years of age. Missing documentation occurred significantly more often for height versus weight and their percentiles in infants ≤2 years versus older children, and in general paediatric versus gastrointestinal patients, with no difference between academic and nonacademic hospitals. Review of documented anthropometric data in discharge letters disclosed that consultants significantly underestimated the deficits in their units compared to documented data. CONCLUSIONS: The survey revealed significant gaps in performance and documentation of anthropometry in the participating hospitals. A resurvey will assess changes in quality of care over time.

Precision nutrition in pediatric IBD: A position paper from the ESPGHAN special interest group for basic science and translational research, the IBD Porto group, and allied health professionals.

Stratified and precision nutrition refers to disease management or prevention of disease onset, based on dietary interventions tailored to a person's characteristics, biology, gut microbiome, and environmental exposures. Such treatment models may lead to more effective management of inflammatory bowel disease (IBD) and reduce risk of disease development. This societal position paper aimed to report advances made in stratified and precision nutritional therapy in IBD. Following a structured literature search, limited to human studies, we identified four relevant themes: (a) nutritional epidemiology for risk prediction of IBD development, (b) food-based dietary interventions in IBD, (c) exclusive enteral nutrition (EEN) for Crohn's disease (CD) management, and (d) pre- and probiotics for IBD management. There is scarce literature upon which we can make recommendations for precision or stratified dietary therapy for IBD, both for risk of disease development and disease management. Certain single-nucleotide polymorphisms related to polyunsaturated fatty acid (PUFA) metabolism may modify the effect dietary PUFA have in increasing the risk of IBD development. Non-colonic CD, mild-to-moderate CD, and high microbiota richness may predict success of EEN and may be used both for prediction of treatment continuation, but also for early cessation in nonresponders. There is currently insufficient evidence to make recommendations for precision or stratified dietary therapy for patients with established IBD. Despite the great interest in stratified and precision nutrition, we currently lack data to support conclusive recommendations. Replication of early findings by independent research groups and within structured clinical interventions is required.

Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts.

OBJECTIVES: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g. METHODS: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-to-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached. RESULTS: In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier. CONCLUSIONS: We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants.

Take-Home Messages from 20 Years of Progress in Dietary Therapy of Inflammatory Bowel Disease.

BACKGROUND: A significant body of literature has interrogated the critical role of diet in the development and management of inflammatory bowel disease (IBD). SUMMARY: This review provides a summary and critical appraisal of the literature in this area, focussing on four distinct themes: nutritional epidemiology, animal and in vitro experiments, enteral nutrition, and food-based dietary therapies. KEY MESSAGES: Nutritional epidemiology and data from experiments in animals indicate that a western-type diet pattern is associated with increased risk of IBD onset. However, these findings have not been consistently replicated in the dietary management of IBD. Exclusive enteral nutrition (EEN) is the only dietary therapy with reproducible evidence of efficacy in the management of active Crohn's disease (CD). Use of EEN may also be useful for improving perioperative outcomes in CD, and as an adjuvant therapy to biologic therapy. Several dietary therapies for CD and ulcerative colitis have been proposed in the literature, but replication in well-controlled studies is needed before their routine use enters the clinical setting. Precision nutritional therapy might be an attractive therapeutic paradigm in a heterogenous disease like IBD. However, no recommendations for personalised dietary therapy can currently be made, and it is imperative we unravel the complex interplay between diet and gut inflammation before we are able to do so. Undoubtedly, diet is of critical importance in the development and management of IBD. However, the exact mechanism by which diet causes gut inflammation is still elusive, and dietary guidance is difficult to formulate.

Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn's disease.

BACKGROUND: There is a clinical need to develop biomarkers of small bowel damage in coeliac disease and Crohn's disease. This study evaluated intestinal fatty acid binding protein (iFABP), a potential biomarker of small bowel damage, in children with coeliac disease and Crohn's disease. METHODS: The concentration iFABP was measured in plasma and urine of children with ulcerative colitis, coeliac disease, and Crohn's disease at diagnosis and from the latter two groups after treatment with gluten free diet (GFD) or exclusive enteral nutrition (EEN), respectively. Healthy children (Controls) were also recruited. RESULTS: 138 children were recruited. Plasma but not urinary iFABP was higher in patients with newly diagnosed coeliac disease than Controls (median [Q1, Q3] coeliac disease: 2104 pg/mL 1493, 2457] vs Controls: 938 pg/mL [616, 1140], p = 0.001). Plasma or urinary iFABP did not differ between patients with coeliac on GFD and Controls. Baseline iFABP in plasma decreased by 6 months on GFD (6mo GFD: 1238 pg/mL [952, 1618], p = 0.045). By 12 months this effect was lost, at which point 25% of patients with coeliac disease had detectable gluten in faeces, whilst tissue transglutaminase IgA antibodies (TGA) continued to decrease. At diagnosis, patients with Crohn's disease had higher plasma iFABP levels than Controls (EEN Start: 1339 pg/mL [895, 1969] vs Controls: 938 pg/mL [616, 1140], p = 0.008). iFABP did not differ according to Crohn's disease phenotype. Induction treatment with EEN tended to decrease (p = 0.072) iFABP in plasma which was no longer different to Controls (EEN End: 1114 pg/mL [689, 1400] vs Controls: 938 pg/mL [616, 1140], p = 0.164). Plasma or urinary iFABP did not differ in patients with ulcerative colitis from Controls (plasma iFABP, ulcerative colitis: 1309 pg/mL [1005, 1458] vs Controls: 938 pg/mL [616, 1140], p = 0.301; urinary iFABP ulcerative colitis: 38 pg/mg [29, 81] vs Controls: 53 pg/mg [27, 109], p = 0.605). CONCLUSIONS: Plasma, but not urinary iFABP is a candidate biomarker with better fidelity in monitoring compliance during GFD than TGA. The role of plasma iFABP in Crohn's disease is promising but warrants further investigation. TRIAL REGISTRATION: Clinical Trials.gov, NCT02341248. Registered on 19/01/2015.

YouTube as a Source of Information on Blenderised Tube Feeding.

ABSTRACT: Blenderised tube feeding (BTF) has become an increasingly popular method of nutrition support for long-term tube-fed patients mostly children. This study surveyed perceptions and experiences on BTF shared on YouTube. From 71 videos analysed, attitudes towards BTF were mostly positive (91%) and included psychosocial benefits and improvements in gastrointestinal symptoms; no differences between caregivers and healthcare professionals were observed. Very few speakers (8%) felt there was a lack of support regarding use of BTF in schools and from healthcare professionals, because it is not part of the standard clinical management protocols. The most commonly used food items in blends included carrots (n = 16) and chicken (n = 11), and experiences from those who have used BTF included tips on recipes for blends, storing feeds and ensuring nutritional adequacy. Analysis of YouTube content on BTF was considerably positive and suggests that BTF is feasible and safe way to provide nutrition to tube-fed patients.

The Impact of Compliance During Exclusive Enteral Nutrition on Faecal Calprotectin in Children With Crohn Disease.

ABSTRACT: It remains unclear whether suboptimal response to exclusive enteral nutrition (EEN) in some children with Crohn disease (CD) is explained by poor compliance. The present study measured faecal gluten immunogenic peptides (GIP), a biomarker of gluten intake, in 45 children (3- 17 years) with CD, and explored associations with faecal calprotectin (FC) levels at 33 and 54 days of EEN. FC decreased in patients with undetectable GIP at both 33 and 54 days of EEN (mean decrease, 33 days: -743 mg/kg, 54 days: -1043 mg/kg, P  < 0.001) but not in patients who had detectable levels. At EEN completion, patients with undetectable GIP had a lower FC by 717 mg/kg compared with patients with a positive GIP result (P = 0.042) and demonstrated a greater decline from baseline FC (-69% vs +5%, P = 0.011). Poorer response to EEN is explained in part by diminished compliance. Faecal GIP might be useful as proxy biomarker of EEN compliance.

A Practical Approach to Identifying Pediatric Disease-Associated Undernutrition: A Position Statement from the ESPGHAN Special Interest Group on Clinical Malnutrition.

ABSTRACT: Disease-associated undernutrition (DAU) is still common in hospitalized children and is generally accepted to be associated with adverse effects on disease outcomes; hence making proper identification and assessment essential in the management of the sick child. There are however several barriers to routine screening, assessment, and treatment of sick children with poor nutritional status or DAU, including limited resources, lack of nutritional awareness, and lack of agreed nutrition policies. We recommend all pediatric facilities to 1) implement procedures for identification of children with (risk of) DAU, including nutritional screening, criteria for further assessment to establish diagnosis of DAU, and follow-up, 2) assess weight and height in all children asa minimum, and 3) have the opportunity for children at risk to be assessed by a hospital dietitian. An updated descriptive definition of pediatric DAU is proposed as "Undernutrition is a condition resulting from imbalanced nutrition or abnormal utilization of nutrients which causes clinically meaningful adverse effects on tissue function and/or body size/composition with subsequent impact on health outcomes." To facilitate comparison of undernutrition data, it is advised that in addition to commonly used criteria for undernutrition such as z score < -2 for weight-for-age, weight-for-length, or body mass index <-2, an unintentional decline of >1inthese z scores over time should be considered as an indicator requiring further assessment to establish DAU diagnosis. Since the etiology of DAU is multifactorial, clinical evaluation and anthropometry should ideally be complemented by measurements of body composition, assessment of nutritional intake, requirements, and losses, and considering disease specific factors.

The Role of Micronutrients in the Pathogenesis of Alcohol-Related Liver Disease.

AIMS: Chronic alcohol consumption may result in liver injury and chronic liver disease, but other factors are likely to influence disease progression. Malnutrition, specifically micronutrient deficiency, is frequently associated with both alcohol use disorder and chronic liver disease. We hypothesize that micronutrient deficiencies may affect the progression of liver disease in this population. METHODS: Systematic integrative review of the medical literature; electronic search of MEDLINE 1950-2021; studies investigating role of any micronutrient in the acceleration of alcohol-related liver injury in humans or animals. Studies which specifically related to alcoholic hepatitis were excluded. Outcomes were extracted and recorded in tabulated form and discussed narratively. RESULTS: We identified 46 studies investigating the role of micronutrient deficiencies in the pathogenesis of alcohol-related liver disease. Specific micronutrients which were identified included folic acid or related B vitamins (n = 9 studies), Vitamin D (n = 9 studies), magnesium (n = 8 studies), zinc (n = 8 studies) and selenium (n = 12 including one systematic review). Observational evidence suggests a potential role of magnesium deficiency in accelerating alcohol-related liver injury with weak or negative evidence for other micronutrients. CONCLUSIONS: Magnesium deficiency may increase the risk of alcohol-related liver injury and adverse liver outcomes. However, currently, there is insufficient evidence to support magnesium supplementation except for clinically relevant magnesium deficiency. Long-term prospective cohort studies assessing the impact of micronutrients on liver disease progression in patients with alcohol use disorder are lacking and may help determine whether there is a causal role for micronutrient deficiencies in alcohol-related liver injury.

Evaluation of Body Composition in Paediatric Osteogenesis Imperfecta.

Osteogenesis Imperfecta (OI) is a skeletal disorder characterised by a predisposition to recurrent fractures and bone deformities. Clinically OI is defined by features such as short stature, however, less is known regarding body composition. Assess body composition, both lean mass and fat mass, in a paediatric OI population. Children with OI attending the Bone service at the Royal Hospital for Children Glasgow were included; who had a dual-energy x-ray absorptiometry (DXA) scan performed 2015-2018. Height and body-mass-index (BMI) were converted to standard-deviation scores (SDS) using UK population references. DXA-derived lean mass and fat mass were used to generate lean-mass-index (LMI) and fat-mass-index (FMI) by dividing the covariates by height squared. LMI and FMI were converted to age-and-gender-adjusted SDS using DXA data from 198 local healthy children. Thirty-eight children (20 males) with median age 11.95 (range: 4.8, 18.3) years were included. Median height SDS was -1.08 (-3.64, 1.62) and was significantly lower than the healthy population (p<0.0001). Median BMI SDS was -0.10 (-2.31, 2.95), and not significantly different from the healthy population (p = 0.53). Median LMI SDS was -2.52 (-6.94, 0.77), and significantly lower than healthy controls (p<0.0001); 61% (23/38) had an SDS below -2.0. Median FMI SDS was 0.69 (-0.45, 2.72), significantly higher than healthy controls (p < 0.0001). BMI SDS cut-offs of -0.15 and 1.33, from ROC analysis, identified children with LMI SDS <-2, with a positive predictive value of 95% and a negative predictive value of 70%; and FMI SDS >2 with a positive predictive value of 44% and a negative predictive value of 100%. A contemporary population of children with ranging severities of OI present with significant reduction in height and lean mass, and relatively high fat mass. Standard BMI SDS cut-offs for identifying children with malnutrition and obesity have poor prognostic validity in OI.

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.

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).

Role of Dietary Factors, Food Habits, and Lifestyle in Childhood Obesity Development: A Position Paper From the European Society for Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

ABSTRACT: Childhood obesity has high societal and economic impact but current treatment approaches are sub-optimal. In the last decade, important studies have been conducted aiming to identify strategies to prevent obesity during critical periods of life. Updated recommendations for childhood obesity prevention are needed. We present data from systematic reviews and meta- analysis, randomised controlled trials (RCTs) and large observational studies, published from 2011 onwards that consider the possible role of the following factors in obesity development: breast-feeding; macronutrient composition and method of complementary feeding; parenting style; dietary patterns; sugar-sweetened beverage consumption; eating behaviour (eg, skipping breakfast, family dinners. etc); meal frequency and composition (fast foods, snacking), portion size; dietary modulators of gut microbiota (including pre-, pro-, and synbiotics); physical activity and sedentary behaviour. We used the Medline database and the Cochrane Library to search for relevant publications. Important research gaps were also identified. This position paper provides recommendations on dietary factors, food habits, and lifestyle to prevent childhood obesity development, based on the available literature and expert opinion. Clinical research and high-quality trials are urgently needed to resolve numerous areas of uncertainty.

Nutritional Management of the Critically Ill Neonate: A Position Paper of the ESPGHAN Committee on Nutrition.

OBJECTIVES: The nutritional management of critically ill term neonates and preterm infants varies widely, and controversies exist in regard to when to initiate nutrition, mode of feeding, energy requirements, and composition of enteral and parenteral feeds. Recommendations for nutritional support in critical illness are needed. METHODS: The ESPGHAN Committee on Nutrition (ESPGHAN-CoN) conducted a systematic literature search on nutritional support in critically ill neonates, including studies on basic metabolism. The Medline database and the Cochrane Library were used in the search for relevant publications. The quality of evidence was reviewed and discussed before voting on recommendations, and a consensus of 90% or more was required for the final approval. Important research gaps were also identified. RESULTS: This position paper provides clinical recommendations on nutritional support during different phases of critical illness in preterm and term neonates based on available literature and expert opinion. CONCLUSION: Basic research along with adequately powered trials are urgently needed to resolve key uncertainties on metabolism and nutrient requirements in this heterogeneous patient population.

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.

The impact of food additives, artificial sweeteners and domestic hygiene products on the human gut microbiome and its fibre fermentation capacity.

PURPOSE: This study investigated the effect of food additives, artificial sweeteners and domestic hygiene products on the gut microbiome and fibre fermentation capacity. METHODS: Faecal samples from 13 healthy volunteers were fermented in batch cultures with food additives (maltodextrin, carboxymethyl cellulose, polysorbate-80, carrageenan-kappa, cinnamaldehyde, sodium benzoate, sodium sulphite, titanium dioxide), sweeteners (aspartame-based sweetener, sucralose, stevia) and domestic hygiene products (toothpaste and dishwashing detergent). Short-chain fatty acid production was measured with gas chromatography. Microbiome composition was characterised with 16S rRNA sequencing and quantitative polymerase chain reaction (qPCR). RESULTS: Acetic acid increased in the presence of maltodextrin and the aspartame-based sweetener and decreased with dishwashing detergent or sodium sulphite. Propionic acid increased with maltodextrin, aspartame-based sweetener, sodium sulphite and polysorbate-80 and butyrate decreased dramatically with cinnamaldehyde and dishwashing detergent. Branched-chain fatty acids decreased with maltodextrin, aspartame-based sweetener, cinnamaldehyde, sodium benzoate and dishwashing detergent. Microbiome Shannon α-diversity increased with stevia and decreased with dishwashing detergent and cinnamaldehyde. Sucralose, cinnamaldehyde, titanium dioxide, polysorbate-80 and dishwashing detergent shifted microbiome community structure; the effects were most profound with dishwashing detergent (R2 = 43.9%, p = 0.008) followed by cinnamaldehyde (R2 = 12.8%, p = 0.016). Addition of dishwashing detergent and cinnamaldehyde increased the abundance of operational taxonomic unit (OTUs) belonging to Escherichia/Shigella and Klebsiella and decreased members of Firmicutes, including OTUs of Faecalibacterium and Subdoligranulum. Addition of sucralose and carrageenan-kappa also increased the abundance of Escherichia/Shigella and sucralose, sodium sulphite and polysorbate-80 did likewise to Bilophila. Polysorbate-80 decreased the abundance of OTUs of Faecalibacterium and Subdoligranulum. Similar effects were observed with the concentration of major bacterial groups using qPCR. In addition, maltodextrin, aspartame-based sweetener and sodium benzoate promoted the growth of Bifidobacterium whereas sodium sulphite, carrageenan-kappa, polysorbate-80 and dishwashing detergent had an inhibitory effect. CONCLUSIONS: This study improves understanding of how additives might affect the gut microbiota composition and its fibre metabolic activity with many possible implications for human health.

Assessment and Interpretation of Vitamin and Trace Element Status in Sick Children: A Position Paper From the European Society for Paediatric Gastroenterology Hepatology, and Nutrition Committee on Nutrition.

Assessment of vitamin and trace element status (VTE) is important in the clinical management of the sick child. In this position paper, we present the various assessment methods available to the clinical practitioner, and critically discuss pitfalls with interpretation of their results. There are 4 main approaches to assess the VTE body status of an individual patient including clinical examination, dietary assessment, and measurement of direct and indirect biomarkers of VTE in biological samples. Clinical signs of VTE deficiencies usually present only when body stores are substantially depleted and are often difficult to detect or differentiate from other nonnutrient-related causes. In isolation, dietary assessment of micronutrients can be inaccurate and imprecise, in disease and in individual patient assessment but may be useful to complement findings from other VTE assessment methods. Use of biomarkers is the most common approach to assess VTE status in routine practice but in the presence of systemic inflammatory response and in the absence of appropriate paediatric reference intervals, interpretation of biomarker results might be challenging and potentially mislead clinical practice. The use of a multimodal approach, including clinical examination, dietary assessment, and laboratory biomarkers is proposed as the optimal way to ascertain the VTE status of individual patients. In the presence of acute inflammatory conditions, VTE measurements in plasma should be replaced by biomarkers not affected by systemic inflammatory response or delayed until inflammatory state is resolved.