Effect Of Exclusive Enteral Nutrition Research Articles

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 (TEMRA), 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.

P976 Treatment with exclusive enteral nutrition (EEN) impacts the peripheral blood mononuclear cell profile of paediatric patients with Crohn’s disease

Abstract Background Background: Despite its established clinical efficacy, the immunological effects of exclusive enteral nutrition (EEN) in Crohn’s disease (CD) are yet to be elucidated. This study investigated the impact of EEN on circulating peripheral blood mononuclear cells (PBMCs) and how any effects observed varied according to clinical response to treatment. Methods Methods: Children with active CD received EEN for eight weeks as their sole induction treatment. Blood and faecal samples were collected prior to EEN and upon EEN completion. PBMCs were isolated, stained and analysed using flow cytometry. Differences in PBMCs types were compared during EEN. Faecal calprotectin was measured with ELISA. Absence of gluten immunogenic peptide (GIP) in faeces was used as a proxy marker of EEN compliance. Results Results: Nine participants were recruited (Table 1), three of whom initiated azathioprine during their course of EEN. Following treatment with EEN a decrease in the relative number and frequency of circulating effector memory CD8+ T cells re-expressing CD45RA (TEMRA) was observed with a corresponding increase in the frequency of circulating central and effector memory CD8+ T cells (Fig. 1). When we excluded participants that commenced thiopurines during their course of EEN a decrease in the relative number of circulating TEMRA CD8+ T cells persisted and a decrease in naïve CD8+ T cells in the blood was also observed. Participants who demonstrated a decrease in faecal calprotectin 50% following treatment with EEN (n= 5) also demonstrated an increase in the frequency of circulating central memory CD8+ T cells. When focussing on participants (n=7) within our cohort who demonstrated a high-level of compliance (undetected GIP in faeces) during EEN, we again observed a decrease in number of TEMRA CD8+ T cells in blood alongside an increase in the frequency of circulating central and effector memory CD8+ T cells. Conclusion Conclusion: We observed significant changes in CD8+ T cell populations in the peripheral blood of children following treatment with EEN. These changes were observed irrespective of background immunomodulator use and persisted in participants which achieved >50% decrease in FC or demonstrated compliance to EEN. Our observed changes in CD8+ T cell populations, particularly the consistent increases in circulating effector and memory CD8+ T cells, are likely a consequence of the actions of EEN in decreasing the diversity and composition of the gut bacteria, therefore reducing the recruitment of effector/memory cells from the blood into the intestine.

Diet prevents the expansion of segmented filamentous bacteria and ileo-colonic inflammation in a model of Crohn’s disease

BackgroundCrohn’s disease (CD) is associated with changes in the microbiota, and murine models of CD-like ileo-colonic inflammation depend on the presence of microbial triggers. Increased abundance of unknown Clostridiales and the microscopic detection of filamentous structures close to the epithelium of TnfΔARE mice, a mouse model of CD-like ileitis pointed towards segmented filamentous bacteria (SFB), a commensal mucosal adherent bacterium involved in ileal inflammation.ResultsWe show that the abundance of SFB strongly correlates with the severity of CD-like ileal inflammation in two mouse models of ileal inflammation, including TnfΔARE and SAMP/Yit mice. SFB mono-colonization of germ-free TnfΔARE mice confirmed the causal link and resulted in severe ileo-colonic inflammation, characterized by elevated tissue levels of Tnf and Il-17A, neutrophil infiltration and loss of Paneth and goblet cell function. Co-colonization of SFB in human-microbiota associated TnfΔARE mice confirmed that SFB presence is indispensable for disease development. Screening of 468 ileal and colonic mucosal biopsies from adult and pediatric IBD patients, using previously published and newly designed human SFB-specific primer sets, showed no presence of SFB in human tissue samples, suggesting a species-specific functionality of the pathobiont. Simulating the human relevant therapeutic effect of exclusive enteral nutrition (EEN), EEN-like purified diet antagonized SFB colonization and prevented disease development in TnfΔARE mice, providing functional evidence for the protective mechanism of diet in modulating microbiota-dependent inflammation in IBD.ConclusionsWe identified a novel pathogenic role of SFB in driving severe CD-like ileo-colonic inflammation characterized by loss of Paneth and goblet cell functions in TnfΔARE mice. A purified diet antagonized SFB colonization and prevented disease development in TnfΔARE mice in contrast to a fiber-containing chow diet, clearly demonstrating the important role of diet in modulating a novel IBD-relevant pathobiont and supporting a direct link between diet and microbial communities in mediating protective functions.8ntX7JCRAmgBnFgN24WWkMVideo

Review article: Mechanisms underlying the effectiveness of exclusive enteral nutrition in Crohn's disease.

Exclusive enteral nutrition (EEN) induces remission and mucosal healing in patients with Crohn's disease, but the mechanism of action remains unknown. To outline current understanding of the mechanisms of action of EEN. From a comprehensive literature search, published data were critically examined in a narrative review. Multiple potential mechanisms of action have been identified. EEN optimises nutritional status. Differences in gut microbiota in terms of overall diversity and taxonomic community structure are observed between responders and non-responders to EEN. Therapy with EEN alters microbial metabolites (including faecal short-chain fatty acids, amino acids, branched-chain amino acids and sulphide) and faecal pH. Epithelial effects and restoration of barrier function, as well as changes in mucosal cytokine profiles and T-cell subsets are observed in responders to EEN. The impact of inclusion or exclusion of specific dietary components may be of importance, but putative detrimental components are found in many formulas. A major challenge in interpreting these findings is that they often contradict or change in opposite directions to what is considered 'beneficial'. It is difficult to differentiate between the observations following EEN being driven by EEN per se and those associated with resolving inflammation. The mechanisms of action of EEN are likely to involve a complex interplay between host mucosal immune response and luminal environment, but the identity of key factors remains poorly understood. A better definition of pathogenic factors may aid in developing more targeted dietary treatment and provide insights into the pathogenesis of Crohn's disease.

DOP52 The faecal bacterial and fungal microbiome of newly-diagnosed, treatment naïve children with Crohn’s disease and the modifying effects of exclusive enteral nutrition and re-introduction of habitual diet

Abstract 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; p<0.001). Treatment with EEN induced drastic changes in mycobiome composition (β diversity), which were more profound and more variable than the effects observed for the bacterial community. Of the OTUs with abundance significantly lower in CD than healthy controls prior to EEN, one, belonging to S. cerevisiae, significantly decreased during EEN (compared with baseline; p<0.001 and p=0.086 at 30 and 60 days on EEN). Patients whose faecal calprotectin was low (<250 mg/kg) during food reintroduction had a lower mycobiome richness than those whose FC was raised (>250 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.

Exploring Different Effects of Exclusive Enteral Nutrition (EEN) and Corticosteroids on the Gut Microbiome in Crohn's Disease Based on a Three-Stage Strategy.

The objective of this study was to compare the efficacy of exclusive enteral nutrition (EEN) and corticosteroids on the gut microbiome in Crohn's disease. Methods. Data were collected for 16 patients newly diagnosed with CD as the test group and 10 healthy volunteers as the control group. The 16 patients were randomly divided into the EEN group and the corticosteroids group. For subsequent analysis, 6 patients in the EEN group with follow-up were enrolled to compare the 0-month, 1-month, and 3-month outcomes. We analyzed and compared gut microbiota between different groups in 3 stages. To evaluate the clinical outcome of treatment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin (HB), albumin (ALB), and Crohn's disease activity (CDAI) were recorded. Results. There are significant differences in microbiota between patients with CD and healthy people, and there are intuitive differences in the main components of the microbiota. 16 patients were included in stage 2, in which both corticosteroids and EEN can induce CD remission well. However, corticosteroids have a greater impact on inflammatory indicators, while EEN has a more obvious effect on nutritional indicators. Principal component analysis suggests that there are different compositional changes in the gut microbiome after corticosteroids and EEN treatment. After 3 months of dynamic observation, we found that EEN can effectively maintain CD remission, reduce inflammatory indicators, and improve nutritional indicators. Conclusions. Both EEN and corticosteroids can increase the diversity of the microbiome in inducing CD remission, while they have different effects on the proportion of microbiome species. This trial is registered with NCT02056418.

Exclusive enteral nutrition remodels the intestinal flora in patients with active Crohn's disease

BackgroundAlthough there are many hypotheses, the pathogenesis of Crohn's disease (CD) is not completely clear so far. Exclusive enteral nutrition (EEN) is a routine measure in the treatment of active CD. We aimed at investigating the impact of EEN on patients with active CD from microbial metabolomics.Methods16S-rDNA sequencing technology and gas chromatography–mass spectrometer analysis were employed to investigate the modification of the intestinal flora and fecal short-chain fatty acid (SCFA) during the EEN.ResultsSeven patients with CD, who conducted EEN, were followed up successfully in the present study. The 8-week EEN resulted in a remission of the condition of subjects with active CD, as revealed by a significant decrease in erythrocyte sedimentation rate (ESR) (P = 0.018), C-reactive protein (CRP) (P = 0.028), and Crohn’s disease activity index (CDAI) (P = 0.018). The nutrition of the subjects was improved after an 8-week treatment course with EEN, which was associated with an increase in body mess index (BMI) (P = 0.018) and serum albumin (ALB) (P = 0.018) levels. Furthermore, our investigations revealed a significantly increased abundance of Firmicutes paralleled by decreased levels of Proteobacteria. With respect to the genus, five species of bacteria including Ruminococcus (P = 0.01), Lachnospiraceae (P = 0.02), Anaerotruncus (P = 0.04), Flavonifractor (P = 0.04), and Novosphingobium (P = 0.05) showed significantly increased abundance. This was accompanied by relative changes in fecal short-chain fatty acids levels. Moreover, we successfully constructed a stable model by combining these five significantly different genera to predict the therapeutic effect of EEN on patients with CD (AUC = 0.9598).ConclusionsThe findings indicated that EEN can alleviate the condition and the nutrition of patients with active CD by regulating the intestinal flora and influencing the expression level of fecal short-chain fatty acids.

P059 Diet controls segmented filamentous bacteria in driving Crohn’s disease-like inflammation in TNFdeltaARE mice

Abstract Background Crohn’s disease (CD)-like inflammation in TNFdeltaARE mice (ARE) mice is triggered by dysbiotic gut microbial communities. Similar to the therapeutic effect of exclusive enteral nutrition in CD, dietary intervention using semi-synthetic experimental diet prevents disease development in ARE mice. The aim of this study is to identify the causal microbial cues responsible for CD-like inflammation and to dissect the protective role of diet in ARE mice. Methods Bacterial communities in ARE and wildtype (WT) mice were profiled by 16S rRNA gene sequencing, FISH and qPCR. Germfree WT and ARE mice were colonized with segmented filamentous bacteria (SFB) from dysbiotic ARE mice. Disease activity, cytokine expression, mucosal immune cell infiltrates as well as Paneth and goblet cells phenotypes were assessed in murine ileal and colonic tissue. To assess the influence of diet on disease development, ARE mice were fed either chow, purified semi-synthetic experimental diet (SED) or fiber-rich diet. Impact of SFB on ileo-colonic inflammation was tested in additional mouse models (XIAP-/- and IL10 -/-). Mucosal biopsies from adult and pediatric IBD patients (N=407) were screened for the presence of human SFB using SFB-specific PCR primers. Results Under specific pathogen-free (SPF) conditions, ARE mice developed CD-like ileal inflammation which correlated strongly with increasing abundance of SFB. Mono-colonization of germfree ARE mice with SFB resulted in severe enterocolitis. Parallel to high tissue levels of TNF and IL-17, SPF-mediated inflammation was associated with neutrophil infiltration and the expansion of IFNγ expressing Th1 cells in the mucosa. Loss of Paneth and goblet cell function allowed SFB to penetrate mucus layers towards the epithelium. SED eradicated SFB and completely abolished inflammation in ARE mice. In contrast, fiber-rich diet partially restored SFB colonization and led to increased levels of inflammatory cytokines. SFB mono-colonization of GF XIAP-/- and IL10 -/- failed to induce inflammation, emphasizing host specificity to the mucosa-adherent SFB. Presence of SFB was confirmed in 12 ileal and 11 colonic mucosal biopsies from IBD patients with active or inactive disease. Conclusion We identified a novel pathogenic role of SFB in driving severe CD-like ileo-colonic inflammation characterized by loss of Paneth and goblet cell functions in ARE mice. Detection of SFB in mucosal biopsies of patients with IBD opens new perspectives about therapeutic strategies targeting SFB-mediated processes. Purified diet antagonized SFB colonization and prevented disease development in ARE mice in contrast to fiber-rich diet, clearly demonstrating the important role of diet in modulating a novel IBD-relevant pathobiont.

P391 Unpacking the different popular diets for pediatric Crohn’s disease - concerns around nutritional adequacy

Abstract Background The first line treatment for inducing remission in pediatric Crohn’s disease (CD) is Exclusive Enteral Nutrition (EEN), where a patient drinks a nutritionally complete formula exclusively for, 6 to, 12 weeks. Despite the effectiveness of EEN, some patients may experience challenges including taste fatigue, monotony, and a lack of social participation with meals. Given these challenges, patients may turn to popular or fad diets for managing their disease. These diets are often restrictive, eliminating a number of foods and exacerbating the risk of underlying nutrient deficiencies in this patient population. Methods These case studies involved a nutrient analysis of evidence-based and popular diets for CD, including Crohn’s Disease Exclusion Diet (CDED), CD-TREAT, Specific Carbohydrate Diet (SCD), IBD Anti-inflammatory Diet (IBD-AID), Autoimmune Protocol (AIP) Diet, Gut and Psychology Syndrome (GAPS) Diet, and low FODMAP. Four cases were selected with mild-moderate CD:, 11-year-old and, 16-year-old, both male and female. A nutrient analysis of sample menus of each diet was completed using Food Processor version of, 11.6.0 by ESHA Research. Results were compared to age and gender specific Dietary Reference Intakes (DRIs), population-based dietary intake data, and Health Canada Dietary Guidelines. Results Data are presented for Case, 1, 11-year-old male. Findings were comparable to other age and gender cases. As compared to Acceptable Macronutrient Distribution Ranges (AMDRs), there was a higher percentage of energy from fats and lower from carbohydrates for the SCD (% kcal, fat and carbohydrate respectively:, 59%;, 30%), IBD-AID (52%;, 37%), AIP Diet (50%;, 20%) and GAPS Diet (60%, 21%). Saturated fat intake exceeded recommendations (>10% of energy intake) for CDED (% kcal, 14%) CD Treat (17%), SCD (11%), AIP Diet (15%) and GAPS Diet (20%). Both vitamin D and/or calcium intake were below the Recommended Dietary Allowance (RDA) respectively for CDED (% RDA, vitamin D and calcium respectively:, 89%;, 86%), SCD (23%;, 53%), AIP Diet (14%;, 23%), low FODMAP Diet (4%, 96%) and GAPS Diet (calcium, 58%). Adolescent females versus males between the ages of, 14–18 years may be at greater risk of inadequate nutrient intake, given the general increase in nutrient requirements yet lower caloric needs. Conclusion Given the increase in awareness and interest in popular diets for Crohn’s disease, it is imperative that clinicians are aware of the risks of inadequate nutrient intake with restrictive diets.

Dietary triggers of gut inflammation following exclusive enteral nutrition in children with Crohn\u2019s disease: a pilot study

BackgroundThe 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.MethodsNutrient 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.ResultsIntakes 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.ConclusionsThis 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).

Diet and gut microbiota manipulation for the management of Crohn's disease and ulcerative colitis.

The aetiology of inflammatory bowel disease (IBD) is multifactorial, with diet and gut microbiota playing an important role. Nonetheless, there are very few studies, particularly clinical research, which have explored the interaction between diet and gut microbiota. In the current review, we summarise the evidence from clinical trials exploring the interactions between the gut microbiota and diet in the management of IBD. Data from the effect of exclusive enteral nutrition (EEN) on the gut microbiota of children with active Crohn's disease (CD), receiving induction treatment, offer opportunities to understand the role of gut microbiota in underlying disease pathogenesis and develop novel dietary and pharmacological microbial therapeutics. In contrast, the evidence which links the effectiveness of food-based dietary therapies for IBD with mechanisms involving the gut microbiota is far less convincing. The microbial signals arising from these dietary therapies are inconsistent and vary compared to the effects of effective treatment with EEN in CD.

DOP66 The effect of exclusive enteral nutrition on circulating inflammatory protein levels in paediatric patients with Crohn’s Disease

Abstract 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 <50% decrease in FC were classed as FC non-responders. 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 <12.5 points). 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

Randomised clinical trial: exclusive enteral nutrition versus standard of care for acute severe ulcerative colitis.

Intravenous corticosteroids are the mainstay of therapy for acute severe ulcerative colitis (ASUC), but 30%-40% of patients fail to respond. To investigate the effectiveness of exclusive enteral nutrition (EEN) as adjunctive therapy to intravenous corticosteroids in patients with ASUC. This was an open-label randomised controlled trial, in which patients who were admitted with ASUC between August 2018 and May 2020 were randomised 1:1 to EEN or standard of care (SOC). Patients on EEN received a semi-elemental formula for 7days along with SOC. The primary outcome was corticosteroid failure, defined by the need for salvage medical therapy or colectomy. Faecal microbial analysis was performed on day 1 and day 7 by 16s ribosomal RNA sequencing in some patients. Of 62 patients (mean age 35.3±12.1years, 40% male), 32 were randomised to EEN and 30 to SOC. Corticosteroid failure was lower on EEN compared to SOC (intention-to-treat analysis 25% vs 43%, P=0.051; per protocol analysis 19% vs 43%, P=0.04), without any difference in colectomy rate (9% vs 13%; P=0.41). Patients on EEN had a shorter hospital stay [median (range) 10 (8-17) vs 13 (8-24) days; P=0.04], higher day 7 albumin level (34±4 vs 29±3g/L, P<0.01), greater reduction in serum C-reactive protein and faecal calprotectin levels (both P=0.04) and a lower composite outcome of colectomy/hospitalisation at 6months (16% vs 39%; P=0.045) compared to SOC. Patients on EEN showed increased abundance of Erysipelotrichaceae on day 7, with reduced Bifidobacterium and Veillonellaceae compared to SOC. EEN for 7days may augment corticosteroid responsiveness in patients with ASUC. (REF/2018/05/019844; CTRI/2020/06/025989).

Effect of Exclusive Enteral Nutrition on Th17 Cells in Juvenile Rats with Inflammatory Bowel Disease.

The objective was to investigate the effect of exclusive enteral nutrition (EEN) on T helper (Th) 17 cells by observing the effects of EEN on colon and serum interleukin (IL)-17A levels in juvenile inflammatory bowel disease (IBD) rat models and to reveal the potential mechanism of the therapeutic effect of EEN on IBD. ATNBS-induced IBD rat model was established. Feeding Peptison, a type of enteric nutrition (EN) for EEN-IBD group and EEN group, normal feed for IBD model group and control group for six consecutive days. Four groups of juvenile rats were sacrificed on day 7. The pathology of the intestinal mucosa was examined, the expression of IL-17A in serum was detected by ELISA, and the expression of IL-17A in intestinal tissue was detected by both western blot and real-time PCR (RT-PCR). Diarrhea, bloody stools, and weight loss were found in both the IBD group and the EEN-IBD group. After 5 days of EEN feeding, the stool characteristics, and blood in the stools of the rats in the EEN-IBD group were significantly relieved compared with those of the IBD group. There was no significant difference in the body mass growth rate between the IBD group and EEN-IBD group (P > 0.05). The growth rate of the EEN group was 51.29 ± 3.61%, which was significantly lower than that of the control group (60.17 ± 9.32%) with P < 0.05. The disease activity index (DAI) score of the EEN-IBD group was significantly lower than that of the IBD group (P < 0.05). In the IBD group, colonic congestion and edema were obvious, scattered ulcers were observed, and the intestinal mucosa had a large amount of inflammatory cell infiltration. In the EEN-IBD group, the intestinal mucosa was slightly congested and a small amount of inflammatory cell infiltrated. The serum IL-17A expression level in the IBD group was significantly higher than in the EEN-IBD group, control group, and EEN group (P < 0.05). Both the gene and protein expressions of IL-17A in the intestinal tissue of the EEN-IBD group were significantly lower than in the IBD group (P < 0.01), and it was significantly higher in the IBD group than in the control and EEN groups (P < 0.01). EEN effectively reduced the intestinal inflammation in the juvenile rats with IBD. The mechanism could be related to the regulation of Th17 cells and the expression of the corresponding cytokine, IL-17A. EEN may play a role in downregulating the expression of IL-17A in the intestinal mucosa.

Effect of Exclusive Enteral Nutrition on the Disease Process, Nutrition Status, and Gastrointestinal Microbiota for Chinese Children With Crohn's Disease.

The aim of this study was to prospectively study the effect of exclusive enteral nutrition (EEN) treatment on Chinese pediatric Crohn's disease (CD) patients. Thirty-one newly diagnosed CD patients were enrolled in this study and treated with EEN for 8 weeks. Twelve healthy controls (HCs) donated their fecal samples. Statistical methods were used to compare the differences. According to the Simple Endoscopic Score for CD (SES-CD) at the end of the EEN treatment, 21 patients with SES-CD ≤4 were classified into the remission group (CD-RE), and 10 patients with SES-CD >4 were classified into the nonremission group (CD-NRE). After EEN therapy, there was a significant decrease in the SES-CD, the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), and fecal calprotectin (FCP) in the CD-RE group (all P < .001). The wPCDAI and FCP also decreased in the CD-NRE group (both P < .05). In terms of nutrition improvement, the CD-RE group patients showed more improvement in weight gain, hemoglobin, and serum albumin level than the CD-NRE group patients (all P < .05). For the microbiota, the CD patients had a lower bacterial diversity and different bacterial community compared with HCs. EEN increased overall diversity and was able to shift the dysbiosis in CD patients toward a healthier state. Absence of improvement in wPCDAI and Shannon index at 2 weeks predicts poor response at the end of EEN. EEN can be used in most Chinese pediatric CD patients to induce remission and improve nutrition.

Effect of Exclusive Enteral Nutrition and Corticosteroid Induction Therapy on the Gut Microbiota of Pediatric Patients with Inflammatory Bowel Disease.

Introduction: Exclusive enteral nutrition (EEN) and corticosteroids (CS) are effective induction therapies for pediatric Crohn’s Disease (CD). CS are also therapy for ulcerative colitis (UC). Host–microbe interactions may be able to explain the effectiveness of these treatments. This is the first prospective study to longitudinally characterize compositional changes in the bacterial community structure of pediatric UC and CD patients receiving EEN or CS induction therapy. Methods: Patients with diagnoses of CD or UC were recruited from McMaster Children’s Hospital (Hamilton, Canada). Fecal samples were collected from participants aged 5–18 years old undergoing 8 weeks of induction therapy with EEN or CS. Fecal samples were submitted for 16S rRNA sequencing. The Shannon diversity index and the relative abundance of specific bacterial taxa were compared using a linear mixed model. Results: The clustering of microbiota was the highest between patients who achieved remission compared to patients still showing active disease (p = 0.029); this effect was independent of the diagnosis or treatment type. All patients showed a significant increase in Shannon diversity over the 8 weeks of treatment. By week 2, a significant difference was seen in Shannon diversity between patients who would go on to achieve remission and those who would not. Conclusion: The gut microbiota of pediatric UC and CD patients was most influenced by patients’ success or failure to achieve remission and was largely independent of the choice of treatment or disease type. Significant differences in Shannon diversity indices occurred as early as week 2 between patients who went on to achieve remission and those who continued to have active disease.

Preoperative enteral nutrition in adults with complicated Crohn's disease: Effect on disease outcomes and gut microbiota

ObjectivesThe use of exclusive enteral nutrition (EEN) in patients with Crohn's disease (CD) before surgical resection can reduce disease activity and improve nutritional status. The mechanism of EEN action is unclear, but it might involve modulation of the intestinal microbiota. The aim of this study was to evaluate the effects (namely changes in gut microbiota) of preoperative EEN in adults with complicated CD referred to surgery. MethodsThis was a prospective study of adult patients with CD referred to surgery. Patients with body mass index <18.5 kg/m2, weight loss >10 %, serum albumin <3 g/dL, or a combination of some or all three, received EEN for ≥2 wk. The effects of EEN on clinical (Harvey–Bradshaw Index [HBI]) and laboratory markers (C-reactive protein [CRP], serum albumin, and fecal calprotectin) and fecal microbiota were analyzed after EEN (before surgery) and 6 mo later. We used 16 S rRNA gene sequencing to determine changes in the fecal microbiota. ResultsFifteen patients were included, of whom 60% were men with a mean age of 45.4 ± 19.1 y. Of those, 10 received EEN. The median duration of preoperative EEN was 41.5 d (15–70 d). During EEN, there was a significant reduction in mean HBI (8.7 ± 1.9 versus 4.1 ± 2.4; P = 0.001) and CRP (11.7 ± 10.3 versus 0.8 ± 0.8 mg/dL; P = 0.008) and an increase in serum albumin (3.1 ± 0.6 versus 4 ± 0.6 g/dL; P = 0.022). Two patients did not require surgery after EEN. The overall microbial composition changed after EEN (Permutational analysis of variance test, P = 0.046) and there was a significant reduction in α diversity (8 ± 2.3 versus 5.2 ± 1.5; P = 0.023). EEN significantly changed the relative abundance of 11 taxonomic operational units (OTUs). At the family level, we found this was mainly due to the decrease in the Enterobacteriaceae family (7 OTUs). Six months after surgery, α diversity was not different from that before or after EEN; at this time point 6 OTUs were significantly different, mainly due to the decrease of Clostridiales order (3 OTUs). The incidence of postoperative complications and hospital length of stay were similar in EEN and immediate surgery groups, as well as clinical and endoscopic recurrence rates 6 mo after surgery. ConclusionsPreoperative EEN improved disease activity and nutritional status in patients with CD referred to surgery. Despite being malnourished, patients given EEN did not have increased postoperative complications compared with well-nourished patients. During EEN, overall microbiota composition changed and α diversity decreased. EEN did not influence postoperative recurrence and gut microbiota 6 mo after surgery.

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

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

Exclusive Enteral Nutrition: Clinical Effects and Changes in Mucosal Cytokine Profile in Pediatric New Inflammatory Bowel Disease.

Exclusive Enteral Nutrition (EEN) is the first-line treatment in children with Crohn’s disease (CD) for induction of remission. However, the mode of action remains conjectural. The aim of this study was to investigate whether the effect of EEN is paralleled by changes in the mucosal cytokine profiles (MCP). Twelve children with new onset inflammatory bowel disease (IBD) received induction treatment with a polymeric EEN. We assessed clinical, endoscopic and histologic scoring before and after EEN. Twelve colonic cytokines were analyzed by Polymerase Chain Reaction (PCR) in six of the IBD patients at onset and after EEN as well as in six non-IBD control children at the diagnostic colonoscopy. Twelve children completed 6 weeks of EEN, except from one child who completed 4 weeks. At the control colonoscopy, 83% were in complete clinical remission. Changes were found in the MCPs of individual patients after EEN. In particular, children with IBD showed significantly higher values of Interleukin (IL)-12β (p = 0.008) and IL-23α (p = 0.02) compared to non-IBD controls at the diagnostic colonoscopy. Furthermore, an overall change in proinflammatory cytokines was noted in the IBD-group after treatment. Further studies are warranted to understand the role of EEN in MCP.

Exclusive enteral nutrition protects against inflammatory bowel disease by inhibiting NF‑κB activation through regulation of the p38/MSK1 pathway.

Although enteral nutrition therapy for inflammatory bowel disease has been confirmed to be an effective treatment method, the exact mechanism responsible for the effects of enteral nutrition remains unclear. The aim of the present study was to investigate the protective effect of exclusive enteral nutrition (EEN) against colitis, and to elucidate the potential mechanisms by inhibiting p65 activation via regulating the p38/mitogen- and stress-activated protein kinase-1 (MSK1) pathway. Experiments were performed by establishing dextran sulfate sodium (DSS)-mice colitis and picrylsulfonic acid solution (TNBS)-induced rat colitis, and the results demonstrated that EEN treatment attenuated body weight loss, colon length shortening and colonic pathological damage caused by colitis. EEN also inhibited inflammatory cells infiltration and decreased myeloperoxidase and inducible nitric oxide synthase activities. Furthermore, EEN significantly reduced the production of pro-inflammatory mediators in serum and the colon. Mechanically, EEN suppressed activation of p65 by inhibiting the p38/MSK1 pathway. In conclusion, the present study demonstrated that EEN attenuated DSS- and TNBS-induced colitis by inhibiting p65 activation via regulating the p38/MSK1 pathway, thus suggesting that EEN is effective in the treatment of colitis.