Exclusive Enteral Nutrition Treatment Research Articles

Mechanisms of Action of Exclusive Enteral Nutrition and Other Nutritional Therapies in Crohn’s Disease

Background and Objectives: Crohn’s disease (CD) is an inflammatory bowel disease (IBD) characterized by transmural inflammation and intestinal fibrosis involving mostly the small intestine and colon. The pathogenic mechanisms of CD remain incompletely understood and cures are unavailable. Current medical therapies are aimed at inducing prolonged remission. Most of the medical therapies such as corticosteroids have substantial adverse effects. Consequently, many dietary therapies have been explored for the management of CD. Up to now, exclusive enteral nutrition (EEN) has been considered the only established dietary treatment for IBD, especially CD. In this article, we aim to give a concise review about the current therapeutic options and challenges in the management of CD and aim to compare the efficacy of EEN with other dietary therapies and update on the possible mechanisms of the benefits of EEN and other nutritional therapies. Methods: We searched the literature up to August 2024 through PubMed, Web of Science, and other sources using search terms such as EEN, nutritional therapy, IBD, Crohn’s disease, ulcerative colitis. Clinical studies in patients and preclinical studies in rodent models of IBD were included in the summary of the therapeutic benefits. Results and Conclusions: EEN involves oral or nasogastric tube feeding of a complete liquid diet with exclusion of normal foods for a defined period (usually 6 to 8 weeks). EEN treatment is demonstrated to have anti-inflammatory and healing effects in CD through various potential pathways, including altering gut bacteria and their metabolites, restoring the barrier function, direct anti-inflammatory action, and indirect anti-inflammatory action by eliminating mechanical stress in the bowel. However, efficacy of other nutritional therapies is not well established in CD, and mechanisms of action are largely unknown.

Treatment of Vedolizumab With Exclusive Enteral Nutrition in Adult Patients With Moderate to Severe Crohn's Disease (Crohn Exclusive Enteral Nutrition Study).

Despite increasing studies confirming the efficacy of vedolizumab (VDZ) in Crohn's disease (CD), improving the responses to this biologic agent remains challenging in clinical practice. In this article, we investigated the efficacy of combined treatment of VDZ and 16-week exclusive enteral nutrition (EEN) in moderately to severely active CD. From October 2020 to October 2023, 81 patients with moderately to severely active CD treated with VDZ from 2 inflammatory bowel disease centers were retrospectively selected. Forty-one patients received treatment of VDZ with concomitant 16-week EEN (VDZ + EEN cohort), and 40 patients received VDZ treatment alone (VDZ cohort). Clinical and biological outcomes were evaluated. Endoscopic response and mucosal healing were assessed by colonoscopy at weeks 16 and 52. There was no statistically significant difference between 2 groups at baseline for demographic and clinical characteristics. Compared with patients treated with VDZ alone, patients in the VDZ + EEN cohort achieved higher rates of clinical response (84.2% vs 40.0%), clinical remission (81.6% vs 30.0%), endoscopic response (91.4% vs 34.6%), including mucosal healing (85.7% vs 26.9%) at week 16. The superiority of VDZ + EEN treatment sustained in maintenance, with 76.7% (vs 33.3%) clinical response, 70.0% (vs 26.7%) clinical remission, 76.9% (vs 33.3%) endoscopic response, and 61.5% (vs 26.7%) mucosal healing at week 52. None of the patients experienced severe adverse events. VDZ with concomitant 16-week EEN might be an effective and optimized approach with solid efficacy in the induction and maintenance treatment of active CD.

Treatment of Active Crohn's Disease With Exclusive Enteral Nutrition Diminishes the Immunostimulatory Potential of Fecal Microbial Products.

Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN. Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing. Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi. This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.

Pre-Diagnosis Diet Predicts Response to Exclusive Enteral Nutrition and Correlates with Microbiome in Pediatric Crohn Disease.

Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN. We analyzed prospectively recorded food frequency questionnaires (FFQs) for pre-diagnosis dietary patterns. Fecal microbiota were sequenced (16SrRNA) at baseline and through an 18-month follow-up period. Dietary patterns, Mediterranean diet adherence, and stool microbiota were associated with EEN treatment outcomes, disease flare, need for anti-tumor necrosis factor (TNF)-α therapy, and long-term clinical outcomes. Ninety-eight patients were included. Baseline disease severity and microbiota were associated with diet. Four dietary patterns were identified by FFQs; a "mature diet" high in fruits, vegetables, and fish was linked to increased baseline microbial diversity, which was associated with fewer disease flares (p < 0.05) and a trend towards a delayed need for anti-TNF therapy (p = 0.086). Baseline stool microbial taxa were increased (Blautia and Faecalibacterium) or decreased (Ruminococcus gnavus group) with the mature diet compared to other diets. Surprisingly, a "pre-packaged" dietary pattern (rich in processed foods) was associated with delayed flares in males (p < 0.05). Long-term pre-diagnosis diet was associated with outcomes of EEN therapy in pediatric CD; diet-microbiota and microbiota-outcome associations may mediate this relationship.

Exclusive Enteral Nutrition Beneficially Modulates Gut Microbiome in a Preclinical Model of Crohn's-like Colitis.

Exclusive enteral nutrition (EEN) is an established dietary treatment for Crohn's disease (CD) by alleviating inflammation and inducing remission. However, the mechanisms of action of EEN are incompletely understood. As CD is associated with gut microbiome dysbiosis, we investigated the effect of EEN on the microbiome in a rat model of CD-like colitis. The rat model of CD-like colitis was established by an intracolonic instillation of TNBS at 65 mg/kg in 250 µL of 40% ethanol. Sham control rats were instilled with saline. Rats were fed ad libitum with either regular pellet food or EEN treatment with a clear liquid diet (Ensure). Rats were euthanized at 7 days. Fecal pellets were collected from the distal colon for 16S rRNA sequencing analysis of gut microbiota. In addition, colon tissues were taken for histological and molecular analyses in all the groups of rats. EEN administration to TNBS-induced CD rats significantly improved the body weight change, inflammation scores, and disease activity index. The mRNA expression of IL-17A and interferon-γ was significantly increased in the colonic tissue in TNBS rats when fed with regular food. However, EEN treatment significantly attenuated the increase in IL-17A and interferon-γ in TNBS rats. Our 16S rRNA sequencing analysis found that gut microbiota diversity and compositions were significantly altered in TNBS rats, compared to controls. However, EEN treatment improved alpha diversity and increased certain beneficial bacteria such as Lactobacillus and Dubosiella and decreased bacteria such as Bacteroides and Enterorhabdus in CD-like rats, compared to CD-like rats with the regular pellet diet. In conclusion, EEN treatment increases the diversity of gut microbiota and the composition of certain beneficial bacteria. These effects may contribute to the reduced inflammation by EEN in the rat model of CD-like colitis.

Exclusive Enteral Nutrition Alleviates Th17-Mediated Inflammation via Eliminating Mechanical Stress-Induced Th17-Polarizing Cytokines in Crohn's-like Colitis.

Exclusive enteral nutrition (EEN) with a liquid diet is the only established dietary treatment for Crohn's' disease (CD). However, the mechanism of action of EEN in CD is unclear. T helper 17 (Th17) immune response plays a critical role in CD. We hypothesized that EEN alleviates Th17 response by eliminating mechanical stress-induced expression of Th17-polarizing cytokines. A rat model of Crohn's-like colitis was established by intracolonic instillation of TNBS (65 mg/kg in 250 µL of 40% ethanol). Control rats were treated with saline. We characterized immunophenotypes and molecular changes of the colon in control and colitis rats with and without EEN treatment. Th17 differentiation was determined using coculture assays. TNBS instillation induced transmural inflammation with stenosis in the inflammation site and a marked increase of Th17-polarizing cytokines interleukin (IL)-6 and osteopontin and the Th17 cell population in the mechanically distended preinflammation site (P-site). EEN treatment eliminated mechanical distention and the increase of IL-6, osteopontin, and Th17 response in the P-site. IL-6 and osteopontin expression was found mainly in the muscularis externa. Mechanical stretch of colonic smooth muscle cells in vitro induced a robust increase of IL-6 and osteopontin. When naïve T cells were cultured with conditioned media from the P-site tissue or stretched cells, Th17 differentiation was significantly increased. Inhibition of IL-6, but not deletion of osteopontin, blocked the increase of Th17 differentiation. Mechanical stress induces Th17-polarizing cytokines in the colon. EEN attenuates Th17 immune response by eliminating mechanical stress-induced IL-6 in Crohn's-like colitis.

P677 Combination of vedolizumab and exclusive enteral nutrition in patients with moderate to severe Crohn’s Disease

Abstract Background Crohn’s disease (CD) is an incurable chronic inflammatory condition of the gut. It causes severe gastrointestinal and extraintestinal complications and is associated with high morbidity, poor quality of life and increased health expenditure. Although increasing randomized controlled tests (RCT) studies demonstrated the premise of efficacy of biologics including vedolizumab in adult patients with active CD, there’re still 60% of patients hard to achieve clinical and endoscopic remission in real-world studies. Here, we investigated the efficacy of combination strategy of vedolizumab and exclusive enteral nutrition (EEN) in moderate to severe active CD treatment. Methods Twenty-eight patients with moderately to severely active CD patients treated with vedolizumab in IBD medical center of Renmin Hospital of Wuhan University in Hubei Province were retrospectively enrolled in this cohort. All patients received EEN for 16 weeks with concomitant vedolizumab standard induction. The clinical response, clinical remission, and fecal calprotectin (FC) normalization was evaluated in short- (week 16) and moderate-term (week 32 and 48). Endoscopic response and mucosal healing were assessed at week 16 and 48 (Figure 1). Figure 1: Study design Results Following vedolizumab intravenous induction and 16-weeks EEN treatment, patients achieved 71.4% (20/28) of clinical remission, 73.1% (19/26) of endoscopic response and 71.4% (20/28) FC normalization at week 16. For moderate-term assessment at week 32, sustainable efficacy of current treatment induced 19/24 (79.2%) of clinical response, 15/24 (62.5%) of clinical remission and 16/24 (66.7%) of FC normalization. Clinical response (15/22, 68.2%) and mucosa healing (14/22, 63.6%) were also observed in over 60% of patients at week 48 since treatment induction (Figure 2,3). Figure 2. Clinical and biochemical endpoints Figure 3. Endoscopic endpoint Conclusion Combination of Vedolizumab and 16-weeks EEN increased clinical and endoscopic outcomes in short and moderate term for patients with moderate to severe Crohn’s Disease.

Global attitudes on and the status of enteral nutrition therapy for pediatric inflammatory bowel disease.

Enteral nutrition (EN) is a diet-remission therapy for inflammatory bowel disease (IBD) that plays a more important role in children than adults. EN includes exclusive enteral nutrition (EEN), partial enteral nutrition (PEN), and maintenance enteral nutrition (MEN). However, EEN remains an unstandardized treatment for pediatric IBD. The types and methods of EN differ around the world. The current study reviewed the EN literature on children with IBD. A total of 12 survey studies were identified that analyzed the current state of EN use, including clinical opinions, implementation methods, treatment course, EEN formula, IBD classification, progress, dietary reintroduction, and patient feedback. The findings revealed that EEN has a strong effect on mild to moderate Crohn's disease (CD). The usage rates of this treatment in different sites were ileum/colon (Paris classification L3) > ileum (L1) > upper digestive tract (L4) > colon (L2) > perianal disease (P) > ulcerative colitis (UC) > extraintestinal lesions. The polymeric formula was the most used EN formulation. New EN diets include a CD exclusion diet (CDED), a specific carbohydrate diet (SCD), and a CD treatment-with-eating (CD-TREAT) diet. Children with IBD responded similarly to EEN administered orally or using a feeding tube. Most guidelines recommended 6-8 weeks of EEN treatment to induce remission. Many clinicians preferred to combine drug medications during EEN and recommended that MEN accounts for at least 25-35% of daily caloric intake. EN remains an unstandardized therapy that requires teamwork across disciplines.

The impact of exclusive enteral nutrition on the gut microbiome and bile acid metabolism in pediatric Crohn's disease

Gut dysbiosis and associated bile acid (BA) metabolism play an important role in the pathogenesis of Crohn's disease (CD). We investigated the impacts of the exclusive enteral nutrition treatment (EEN) on the gut microbiome (GM) and BAs metabolism for patients with CD. Targeted metabolomics analysis and metagenomics analysis were performed in feces to investigate the BA and GM changes of patients before and after 2-months EEN therapy. The Pediatric Crohn's Disease Activity Index (PCDAI) and fecal calprotectin were used to evaluate the severity and mucosal inflammation of CD. A total of 27 newly diagnosed pediatric patients with CD and 27 healthy controls were recruited in this study. Both GM structure and the secondary BA metabolism were significantly impaired in patients, which could return towards normal levels after EEN treatment. The most abundant taxa Firmicutes and 11 BAs were found closely associated with the PCDAI score and fecal calprotectin. Meanwhile, the close interactions between Firmicute bacteria and BAs might contribute to the remission of CD after EEN treatment. The qPCR data further confirmed that the relative expressions of Firmicutes phylum, and genus Flavonifractor and Clostridium V were improved after EEN treatment. Firmicutes bacteria and the balance of primary and secondary BA compositions in the gut were closely associated with the health status of CD disease indicated by the PCDAI score and fecal calprotectin. Understanding the recovery process of gut microbiome and BA metabolism will help us to explore the potential mechanisms of EEN therapy.

Exclusive Enteral Nutrition Exerts Anti-Inflammatory Effects through Modulating Microbiota, Bile Acid Metabolism, and Immune Activities.

Exclusive enteral nutrition (EEN) can induce remission in patients with pediatric Crohn's disease (CD). This study aims to depict EEN's modification of bile acid (BA) metabolism in pediatric CD and explores the effect of the EEN-enriched BA in inhibiting the inflammatory response. The twelve enrolled pediatric CD patients showed BA dysmetabolism, represented by decreased levels of fecal secondary and unconjugated BAs as determined by UPLC-TQMS, which were accompanied by gut microbiota dysbiosis and reduced BA-metabolizing bacteria including Eubacterium and Ruminococcus genera, assessed by shotgun metagenomic sequencing. EEN treatment induced remission in these patients at eight weeks, and nine patients remained in stable remission for longer than 48 weeks. EEN improved BA dysmetabolism, with some enriched BAs, including hyocholic acid (HCA), α-muricholic acid (αMCA), strongly associated with decreased severity of CD symptoms. These BAs were significantly correlated with the increased abundance of certain bacteria, including Clostridium innocuum and Hungatella hathewayi, which express 3β-hydroxysteroid dehydrogenase and 5β-reductase. HCA could suppress TNF-α production by CD4+ T cells in the peripheral blood mononuclear cells (PBMCs) of CD patients. Moreover, intraperitoneal injection of HCA could attenuate dextran sulfate sodium (DSS)-induced mouse colitis. Our data suggests that BA modification may contribute to the EEN-induced remission of pediatric CD.

Outcomes of Pediatric Patients with Crohn's Disease Received Infliximab or Exclusive Enteral Nutrition during Induction Remission.

Background Both exclusive enteral nutrition (EEN) and infliximab (IFX) are recommended as induction therapy for pediatric Crohn's disease (CD). Our aim was to compare long-term disease outcomes of patients initially received with either IFX or EEN. Methods Medical records of newly diagnosed, therapy naïve pediatric patients with CD received with IFX or EEN as induction therapy were retrospectively enrolled. Pediatric Crohn's disease activity index (PCDAI), Crohn's disease endoscopic index of severity (CDEIS), and other clinical data were compared pre- and postinduction therapy in two groups. The sustained remission rates and time coupled with body mass index (BMI) and height for age (HFA) changes were evaluated during more than 2-year long-term follow-up. Results We collected data from 58 children with CD used IFX (23) or EEN (35) as induction remission therapy from January 2015 through June 2021 in our single-center. The median follow-up after starting IFX or EEN was 12.2 months (6.5–18.0months) and 18.9 months (7.1–30.7months), respectively. The proportion clinical and endoscopic remission in EEN (88.57% and 68.75%) was similar with that of IFX (73.91% and 80.77%) after induction therapy. No significant differences were also observed in BMI and HFA recovery between two groups. Among those who achieved clinical or endoscopic remission or endoscopic response, the sustained remission rates and time did not reveal any significant differences for those 10 patients who used 6-mercaptopurine/methotrexate (6-MP/MTX) or 14 patients who used IFX as maintenance treatment during longitudinal follow-up. Conclusions Our study suggested that EEN treatment is similar with IFX therapy in short-term outcomes, and EEN+6-MP/MTX treatment is comparable with IFX+IFX therapy in long-term outcomes.

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.

Effectiveness of induction therapy with exclusive enteral nutrition in pediatric Crohn's disease

To evaluate the effectiveness of induction therapy with exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD). A retrospective analysis was performed on the medical data of 62 children with CD who received EEN in Children's Hospital, Zhejiang University School of Medicine, from March 2013 to August 2021. The medical data included general information and height, weight, Pediatric Crohn's Disease Activity Index (PCDAI), Crohn's Disease Endoscopic Index of Severity, C-reactive protein, erythrocyte sedimentation rate, and serum albumin level before treatment and after 8 weeks of treatment. The changes in the above indicators were compared before and after treatment. Among the 62 children with CD, there were 39 boys (63%) and 23 girls (37%), with a mean age of (11.9±3.0) years at diagnosis. Among the 55 children who completed EEN treatment for at least 8 weeks, 48 (87%) achieved clinical remission at week 8. PCDAI at week 8 was significantly lower than that before treatment (P<0.001). Except for 17 children with involvement of the small intestine alone and 3 children with involvement of the colon who did not receive colonoscopy reexamination, the remaining 35 children with involvement of the colon received colonoscopy reexamination after the 8-week EEN treatment. Of the 35 children, 29 (83%) achieved mucosal healing. As for the 48 children who achieved clinical remission at week 8, there were significant improvements in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P<0.01). As for the 7 children who did not achieve clinical remission at week 8, there were no significant changes in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P>0.05). The 8-week EEN treatment has a good effect on clinical remission and mucosal healing in children with CD. For the children with CD achieving clinical remission, EEN can improve their height and body mass index.

Evaluation of exclusive enteral nutrition and corticosteroid induction treatment in new-onset moderate-to-severe luminal paediatric Crohn’s disease

To induce remission in luminal paediatric Crohn’s disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the “TISKids” study assigned to the conventional treatment arm. Patients were aged 3–17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI) > 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score < 3 without treatment escalation at week 10. Secondary outcomes included proportion of patients without treatment escalation at week 52. In total, 27/47 patients received EEN and 20/47 corticosteroids. At baseline, patient demographics and several inflammation parameters were similar between the two treatment groups. At 10 weeks, clinical remission rates were 7/23 (30%) for EEN and 7/19 (37%) for corticosteroids (p = 0.661). Twenty-nine of 47 consented to endoscopy at 10 weeks, showing endoscopic remission rates without treatment escalation in 2/16 (13%) of EEN-treated patients and in 1/13 (8%) of corticosteroid-treated patients (p = 1.00). At week 52, 23/27 (85%) EEN-treated patients received treatment escalation (median 14 weeks) and 13/20 (65%) corticosteroid-treated patients (median 27 weeks), p = 0.070.Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10. Trial registration number: NCT02517684What is Known:• Endoscopic remission is associated with a low risk of disease progression.• FL-IFX was superior to conventional treatment in achieving and maintaining remission in paediatric patients with moderate-to-severe CD the first year from diagnosis.What is New:• In children with newly diagnosed moderate-to-severe CD, clinical remission rates and endoscopic remission rates without treatment escalation at week 10 were 30% and 13% after EEN and 37% and 8% after corticosteroid induction treatment.• The current treatment target was often not achieved by either EEN or corticosteroid induction treatment after bridging to azathioprine.

A Pilot Study Investigating Faecal Microbiota After Two Dietary Interventions in Children with Juvenile Idiopathic Arthritis

There is evidence for an impact of the gut microbiota on the immune system, which has consequences for inflammatory diseases. Exclusive enteral nutrition (EEN) and the specific carbohydrate diet (SCD) have been demonstrated as effective anti-inflammatory treatments for children with Crohn’s disease. We have previously shown an anti-inflammatory effect from these nutritional treatments in children with juvenile idiopathic arthritis (JIA). The aim of this study was to investigate if improved clinical symptoms after EEN or SCD treatment in children with JIA could be linked to changes in faecal microbiota. We included sixteen patients with JIA (age 7–17 years), six for treatment with EEN and ten with SCD. EEN was given for 3–5 weeks and SCD for 4–5 weeks, with clinical and laboratory status assessed before and after treatment. Faecal samples were analysed for microbiota diversity and composition using 16S rRNA gene sequencing. Analyses of the faecal microbiota showed an effect on the overall composition with both interventions; the most striking result was a decreased relative abundance of the genus Faecalibacterium from EEN and of Bifidobacterium from SCD. The α-diversity decreased significantly from SCD (P = 0.04), but not from EEN (P = 0.22). Despite the study cohorts being small, both EEN and SCD were shown to impact the faecal microbiota. Future larger studies with a focus on metagenomics or metabolomics could possibly reveal a link and clarify the clinical effects of those nutritional regimens.

NOVEL INSIGHTS INTO THE MECHANISM OF ACTION OF EXCLUSIVE ENTERAL NUTRITION IN CROHN’S DISEASE: PRE-CLINICAL STUDY IN A RODENT MODEL OF CROHN’S-LIKE COLITIS

Exclusive enteral nutrition (EEN) is the only established dietary therapy for Crohn’s disease (CD). However, mechanisms of action of EEN in CD are not clear. CD is characterized by recurrent transmural inflammation in the gut. Mechanical stress, associated with inflammatory cell infiltration, edema, fibrosis, and obstruction, is inevitably present in CD tissue. We hypothesized that transmural inflammation causes mechanical stress, which induces expression of mechanosensitive genes such as IL-6 and COX-2 in the gut, and that EEN treatment attenuates inflammation by alleviating the effect of mechanical stress-induced expression of proinflammatory genes in CD.

Is the frequency of dietitian support associated with greater clinical improvements in adults with Crohn's disease undertaking exclusive enteral nutrition?

Exclusive enteral nutrition (EEN) is considered to be an effective, low-risk therapy in the treatment of Crohn's disease (CD). Frequent dietetic support may assist adults to succeed. The present observational study aimed to compare whether the frequency of dietetic support during EEN therapy was associated with differences in clinical and nutritional outcomes across two gastroenterology inflammatory bowel disease services. Site A provided ≥3 visits plus more if clinically indicated and Site B provided weekly support. Eligible patients were adults with active CD recommended to be treated with oral EEN for ≥6 weeks between February 2018 and December 2019. Demographic, anthropometric, clinical, medications, pathology and EEN treatment descriptors were sourced from the medical chart. Descriptive statistics, as well as chi-squared and t tests, were used to compare data between sites. Eighty-four CD patients were eligible (44 ± 14 years, 54% female, baseline Crohn's disease activity index [CDAI] 259.5 ± 113.1, n = 51 Site A) and completed EEN for median (range) 6.1 (1-12) weeks. Most patients (82%, n = 69/84) completed ≥6 weeks of EEN treatment. CDAI score and calprotectin improved across the total sample from pre- to post-EEN by -109.8 ± 92.1 (p < 0.001) and -65 µg g-1 (-65,230 to 4370) (p = 0.002), respectively. Dietitian occasions of service were more frequent at Site B (7 [4-12] occasions vs. 3 [1-8], p < 0.001). However, changes in clinical and biomarker data were similar between sites (p < 0.05). EEN with regular dietetic input resulted in clinical and biochemical improvements for patients with active CD. Tailoring dietetic support based on the client's needs and preference may achieve clinical improvements similar to providing weekly dietetic support to adults on EEN.

Lipidomics reveals significant alterations associated with exclusive enteral nutrition treatment in adult patients with active Crohn's disease.

Crohn's disease (CD), a type of inflammatory bowel disease, is a chronic idiopathic disorder of the gastrointestinal tract with an increasing global incidence. Exclusive enteral nutrition (EEN) is a diet therapy that is effective in the management of active CD with unknown etiology. Lipid metabolism plays an important role in CD and may be associated with EEN treatment. This study compared the plasma lipid profiles before and after EEN in adults with active CD to those of healthy controls (HCs). Eleven adult patients with active CD who received enteral nutrition formula treatment for 12 weeks were included, along with 17 HCs. The profiles of 869 plasma lipid species were measured, and inflammatory and nutrition-associated indices were evaluated in the patients. Nine patients achieved clinical remission following 12 weeks of EEN treatment, and four achieved mucosal healing. Before EEN, 80 lipid species and 17 lipid classes were significantly different between patients with CD and HCs. After EEN treatment, 103 lipid species and 12 lipid classes were significantly different between patients with CD and HCs. Significant changes in 7 lipid classes and 38 lipid species were observed between the pre- vs. post-treatment CD patients. The levels of simplified glucosylceramide series, monogalactosyldiacylglycerol, phosphatidylinositol, phosphatidylserine, and phosphatidylcholine increased, while those of phosphatidylglycerol and phosphatidylinositol diphosphate decreased significantly after EEN. These lipid classes and species were associated with the inflammatory and nutritional indices. Pathway analysis suggested the metabolism of arachidonic acid, glycerophospholipids, linoleate, and phosphatidylinositol phosphate was related to the EEN mechanism. EEN induces alterations in multiple lipid classes and species, leading to clinical improvements. Lipid metabolism may be involved in the EEN anti-inflammatory effect.

Exclusive Enteral Nutrition in Adult Crohn's Disease: an Overview of Clinical Practice and Perceived Barriers.

Recently, the role of nutrition in the management of Crohn’s disease (CD) is of increasing interest and the exploration of novel nutritional interventions to improve long-term management of the disease is challenging. So far, the majority of the studies on the role of exclusive enteral nutrition (EEN) in CD are conducted in the pediatric population and have highlighted the efficacy of EEN for achieving mucosal healing. This implicates that a similar approach would be beneficial in adult patients. However, the evidence for EEN in adults is heterogeneous, with meta-analyses reporting it as inferior to steroids while growing data demonstrate improvement in complicated CD. Currently, EEN is less used in adult patients with IBD. Indeed, the lack of palatability of enteral formula leads to difficulties in acceptance and compliance. The search for more tolerable and still effective diets has become an intense area of research aiming to explore the potential role of diet to control inflammation in patients with CD. Thus, this narrative review provides the state-of-the-art on the use of EEN treatment in CD and highlights the perceived barriers to its implementation in adult CD patients.

Influence of Enteral Nutrition on Gut Microbiota Composition in Patients with Crohn's Disease: A Systematic Review.

The aim of the study was to systematically and comprehensively evaluate whether exclusive enteral nutrition (EEN) has impact on gut microbiota in patients with Crohn’s disease (CD). The databases PUBMED (MEDLINE), SCOPUS and WEB OF SCIENCE were searched. Out of 232 studies, 9 met inclusion criteria. The combined analyzed population consists of 118 patients with CD and treated with EEN with a time of intervention of 2–12 weeks. Studies were conducted in children, with the exception of one study. All applied feeding formulas had similar energy value and composition. The microbiome analysis was based on 16S rRNA gene sequencing of faecal samples. In all studies, EEN treatment decreases inflammatory markers (i.e., hs-CRP and FCP). A change in abundance of numerous bacterial families (Clostridiaceae, Eubacteriaceae, Bacteroidaceae) was noticed, especially in Bacteroidaceae. An increase in families connected to the more severe clinical course (Fusobacteria, Prevotella, Lachnospiraceae) was observed in only 2.5% of CD patients. Our analyses suggest EEN has a beneficial influence on gut microbiome in patients with CD, which is interrelated with clinical patient’s improvement and time of disease remission.