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Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn's disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with Lachnospiraceae and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free Il10-deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles.

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. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has become a catalyst for changing the technological order of human development and has accelerated the formation of new forms of organization and business. The change of technological orders causes uneven development of scientific and technological progress, as a result of which the existing technologies deepen, which become dominant and can be superimposed on the existing technological way of life. The purpose of the study is to substantiate changes in technology orders and to analyze the process of digitization as a new trend in the internationalization of technology transfer based on data on the dynamics of business meetings at brokerage events recorded in the Enterprise Europe Network (EEN). The use of EEN IT platform tools and general scientific methods such as analysis and synthesis, induction and deduction, and historical analysis has confirmed the differences between the fifth and sixth technological orders and demonstrated the search for new ways of development for small businesses. The study formulated a general strategy for the digitization process and recommendations for the internationalization of technology transfer using Enterprise Europe Network tools in a pandemic, which include intensifying business activities using cyberspace, changing existing forms of organization, and innovation for small businesses. This strategy became the basis for the formation of a new methodological paradigm for managing the process of internationalization of technology transfer, taking into account the peculiarities of the domestic economy in a pandemic.

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. [ABSTRACT FROM AUTHOR]

Background: Exclusive enteral nutrition (EEN) supplementation of the standard of care (SOC) augments steroid responsiveness in patients with acute severe ulcerative colitis (ASUC). EEN is known to alter gut microbial composition. The present study investigates EEN-driven gut microbial alterations in patients with ASUC and examines their correlations with clinical parameters., Methods: Stool samples from patients with ASUC (n = 44) who received either EEN-supplemented SOC (EEN group; n = 20) or SOC alone (SOC group; n = 24) for 7 days were collected at baseline (day 0) and postintervention (day 7). Microbiome analysis was carried out using 16S ribosomal RNA gene sequencing followed by data processing using QIIME2 and R packages., Results: Seven-day EEN-conjugated corticosteroid therapy in patients with ASUC enhanced the abundances of beneficial bacterial genera Faecalibacterium and Veillonella and reduced the abundance of Sphingomonas (generalized linear model fitted with Lasso regularization with robustness of 100%), while no such improvements in gut microbiota were observed in the SOC group. The EEN-associated taxa correlated with the patient's clinical parameters (serum albumin and C-reactive protein levels). Unlike the SOC group, which retained its preintervention core microbiota, EEN contributed Faecalibacterium prausnitzii, a beneficial gut bacterial taxon, to the gut microbial core. EEN responders showed enhancement of Ligilactobacillus and Veillonella and reduction in Prevotella and Granulicatella. Analysis of baseline gut microbiota showed relative enhancement of certain microbial genera being associated with corticosteroid response and baseline clinical parameters and that this signature could conceivably be used as a predictive tool., Conclusions: Augmentation of clinical response by EEN-conjugated corticosteroid therapy is accompanied by beneficial gut microbial changes in patients with ASUC., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the effect of early enteral nutrition(EEN) on postoperative recovery and immune function in patients undergoing radical gastrectomy for gastric cancer. Methods: 60 patients with gastric cancer underwent radical gastrectomy in our hospital from June 2011 to January 2014 were divided into EEN group and total parenteral nutrition(TPN) group according to the postoperative nutrition, 30 cases in each group. The recovery and immune function of the two groups were compared. All patients were followed up for 3 years. The progression free survival rate and overall survival rate of the two groups were observed and recorded.Results: The postoperative exhaust time [(2.46±0.78)d vs.(3.85±1.03)d], defecation time [(4.03±1.17)d vs.(5.67±1.23)d], liquid diet time [(5.88±1.30)d vs.(7.26±1.59)d], semi liquid diet time [(7.94±1.85)d vs.(11.01±2.36)d] and length of stay [(14.87±2.56)d vs.(17.54±3.30)d] in EEN group were significantly shorter than those in TPN group, the differences were statistically significant(P<0.05).At postoperative 1 d, the humoral immune indices(Ig A, Ig G, Ig M) and cellular immunity indices(CD3+, CD4+and CD4+/CD8+) of two groups were significantly decreased(P <0.05), which gradually recovered after nutrition support, and the recovery of EEN group was larger than that of TPN group, the difference was statistically significant(P<0.05). The incidence of postoperative complications in EEN group was significantly lower than that in TPN group(13.33% vs. 36.67%, P <0.05). The 1 year, 2 year and 3 year progression free survival rate and overall survival rate of patients in EEN group were higher than those in TPN group, but the differences were not statistically significant(P >0.05). Conclusion: EEN can effectively promote the recovery of intestinal function in patients undergoing radical gastrectomy for gastric cancer, shorten the length of stay, improve the immune function and reduce the incidence of complications, it is worthy of recommendation in clinical practice. [ABSTRACT FROM AUTHOR]

Metabolomic profiling using high resolution mass spectrometry with hydrophilic interaction chromatography was applied to 11 faecal extracts from eleven healthy children and to 43 faecal extracts from eleven children undergoing exclusive enteral nutrition for the treatment of active Crohn's disease (CD) at timepoints before, during (15, 30, and 60 days), and after treatment. Differences between the control and CD samples were identified at each timepoint. An orthogonal partial least square-discriminant analysis (OPLS-DA) model identified eight metabolites that were normally distributed according to Q-Q plots. The OPLS-DA model was able to discriminate the CD samples from the controls at every timepoint, but the model was not able to differentiate the CD samples from one another at the different timepoints during treatment with exclusive enteral nutrition. The differentiated metabolites identified in the CD samples included tyrosine, an ornithine isomer, arachidonic acid, eicosatrienoic acid, docosatetraenoic acid, a sphingomyelin, a ceramide, and dimethylsphinganine. Despite successful treatment, underlying differences remained in the metabolome of the CD patients. These differences dominated the separation of the samples when multivariate methods were applied. [ABSTRACT FROM AUTHOR]

Background and Aims: Exclusive enteral nutrition [EEN] is recommended as a first-line induction therapy for paediatric Crohn's disease [CD] although corticosteroids [CS] are still used commonly. Our aim was to compare short- and long-term disease outcomes of paediatric CD patients initially managed with either EEN or CS. Methods: Medical records of newly diagnosed paediatric CD patients treated with EEN or CS as induction therapy were retrospectively reviewed. To minimise selection bias inherent in observational cohort studies, propensity analysis was carried out. Data on anthropometrics, medical history, and presenting phenotype were collected at time of diagnosis [baseline]; outcomes of interest, including medication use, hospitalisation, surgical procedures, and disease progression were assessed up to 6 years following diagnosis. Results: Of 127 patients reviewed, a total of 111 propensity-score matched CD patients receiving EEN [n = 76] or CS [n = 35] were analysed. By 4-12 weeks of induction therapy, 86.6% of EEN-treated patients achieved remission (Paediatric Crohn's Disease Activity Index [PCDAI] ⩽ 7.5) compared with 58.1% of patients in the CS-treated group [p < 0.01]. Choice of EEN over CS for induction was associated with avoidance of corticosteroids over a 6-year follow-up period. Analysis of long-term linear growth, hospitalisation, need for biologic therapy, or surgical intervention did not reveal any significant differences. Conclusions: These findings suggest that EEN induction therapy is more effective in achieving early remission and is associated with long-term steroid avoidance without increased use of biologics or need for surgery. [ABSTRACT FROM AUTHOR]

The main objective of this study is to analyze the multi-scale spatial variability of the snow water equivalent (SWE). As a first step, the spatial variability of SWE was compared with respect to the latitude and longitude. Local indices were used to characterize different spatial structures. Subsequently, the spatial structures were delineated using a spatial segmentation (multi resolution) approach on physiographic meta-variables. The segmentation was validated using the non-parametric Kruskal-Wallis test applied to the SWE data of each pair of adjacent geographical areas. At the regional scale, the spatial segmentation identified six geographical areas distinguished by their position relative to the different modes of atmospheric circulation variability and the topographic relief. At the local scale, the spatial segmentation highlighted the role of the slope, curvature etc. in the spatial variability of SWE. [ABSTRACT FROM AUTHOR]

Metabolomic profiling using high resolution mass spectrometry with hydrophilic interaction chromatography was applied to 11 faecal extracts from eleven healthy children and to 43 faecal extracts from eleven children undergoing exclusive enteral nutrition for the treatment of active Crohn’s disease (CD) at timepoints before, during (15, 30, and 60 days), and after treatment. Differences between the control and CD samples were identified at each timepoint. An orthogonal partial least square-discriminant analysis (OPLS-DA) model identified eight metabolites that were normally distributed according to Q-Q plots. The OPLS-DA model was able to discriminate the CD samples from the controls at every timepoint, but the model was not able to differentiate the CD samples from one another at the different timepoints during treatment with exclusive enteral nutrition. The differentiated metabolites identified in the CD samples included tyrosine, an ornithine isomer, arachidonic acid, eicosatrienoic acid, docosatetraenoic acid, a sphingomyelin, a ceramide, and dimethylsphinganine. Despite successful treatment, underlying differences remained in the metabolome of the CD patients. These differences dominated the separation of the samples when multivariate methods were applied.

Background: Gastrointestinal fistula (GIF) in severe acute pancreatitis (SAP) is considered as a sparse episode and studied sporadically in the literature. There is paucity of data on the prediction of the effect on risk of GIF in patient with SAP. This study was aimed to investigate risk factors related to GIF in the development of SAP.Methods: The clinical data of 344 patients with SAP from 2011 to 2016 were reviewed retrospectively. All patients were divided into the GIF group and the non-GIF group, and their data analyzed with respect to 15 parameters were applied to explore potential risk factors for GIF in patients with SAP.Results: Of the 344 eligible patients, 52 (15.12%) progressed to GIF. Only occurrence of infected pancreatic and extra-pancreatic necrosis (IPN) (P = 0.004, OR = 3.012) and modified CT severity index (MCTSI) (P = 0.033, OR = 1.183) were proved to be independent risk factors for GIF in patients with SAP, and blood type B (P = 0.048, OR = 2.096, 95% CI: 0.748-3.562) indicated weaker association of risk factor for GIF. The early (48-72 h after admission) enteral nutrition (EEN) (P = 0.016, OR = 0.267) acted as a protective factor.Conclusions: Occurrence of IPN and high MCTSI are independent risk factors for the development of GIF in patients with SAP, blood type B reveals a potential correlation with GIF in patients with SAP. EEN is helpful to prevent the progression of GIF secondary to SAP. [ABSTRACT FROM AUTHOR]

Background: Exclusive Enteral Nutrition (EEN) induction in children with luminal Crohn's disease (CD) gives early mucosal healing (MH), but the long-term benefits of EEN-induced MH are just emerging. Aims & Methods: We prospectively followed an Australian cohort of newly diagnosed children with predominantly luminal CD who completed at least six weeks EEN and with paired clinical Pediatric Crohn's Disease Activity Index (PCDAI), biochemical (C-reactive protein; CRP) and endoscopic assessment at diagnosis and post EEN. All commenced immunomodulators (IMs) early (<3 months from diagnosis) and had a minimum of 1 year follow-up. Complete MH was a simple endoscopic score for Crohn's disease (SES-CD) of 0, and SES-CD⩾1 was ascribed to active endoscopic disease (aED) and further divided into near complete MH (SES 1-3), mild active disease (SES-CD 4-10) and moderate to severe disease (SES-CD>10). The primary outcome was long-term supervised sustained remission (SR) on IMs alone without need for corticosteroids, infliximab (IFX) or surgery. Results: A total of 54 eligible children (33 males) completing EEN induction were analysed. The median duration between pre and post EEN assessments was 60.5 days [interquartile range (IQR), 56-69.5]. Post EEN: clinical remission (PCDAI < 10) was observed in 45/54 (83%), and biochemical remission (PCDAI < 10 and CRP < 5 mg/dl) was observed in 39/54 (72%). Complete MH was observed in 18/54 (33%), near complete in 10/54(19%). SR was superior in those with complete MH vs. aED; 13/18, (72%) vs. 10/36 (28%), p = 0.003 at 1 year, 8/16, (50%) vs. 3/24, (8%), p = 0.008 at 2 years and (8/16, (50%) vs. 1/19, (6%), p = 0.005) at 3 years. Near-complete MH did not lead to superior SR. Conclusions: Only complete MH post EEN induction predicts more favourable SR for up to 3 years. [ABSTRACT FROM AUTHOR]

Background: Impact of first-line induction therapy on medium-term outcomes in the setting of early thiopurine (TP) use in children with Crohn's disease has not been evaluated, in particular whether choice of exclusive enteral nutrition (EEN) over corticosteroids (CS) for induction impacts clinical outcomes at 12 and 24 months.Aims and Methods: In this retrospective study, 89 children from our database with new diagnosis CD and follow-up of at least 2 years following induction with exclusive course of CS or EEN and early, dose-optimized TP (within 6 months from diagnosis) were evaluated. We compared steroid dependency (relapse <3 months of tapering first course CS or inability to wean <10 mg prednisolone), need for IFX, linear growth, and surgical resections over the first 2 years.Results: Choice of EEN over CS induction was associated with reduced linear growth failure (7 vs. 26%, p = 0.02), CS dependency (7 vs. 43%, p = 0.002), and improved primary sustained response to IFX (86 vs. 68%, p = 0.02). Combined CS/IFX-free remission and surgical resection rates were similar.Conclusion: In the setting of early TP commencement, EEN induction is superior to CS induction for reducing growth failure, CS dependency, and loss of response to IFX over the first 2 years. [ABSTRACT FROM AUTHOR]

Nutritional therapy is well established as a means to induce remission in active Crohn’s disease (CD). Evidence indicates that exclusive enteral nutrition (EEN) therapy for CD both alters the intestinal microbiota and directly suppresses the inflammatory response in the intestinal mucosa. However, the pathway(s) through which EEN suppresses inflammation is still unknown. Therefore, the aim of the current study was to use microarray technology to investigate the major pathway by which polymeric formula (PF) alters inflammatory processes in epithelial cells in vitro. HT-29 cells were grown to confluence and then co-cultured with tumour necrosis factor (TNF)-α (100 ng/ml) for 5 h in the presence or absence of PF, as used for EEN. Following incubation, RNA was extracted and subjected to polymerase chain reaction (PCR) and microarray analysis. Enzyme-linked immunosorbent assays were employed to evaluate cytokine protein levels. Neither TNF-α nor PF had a toxic effect on cells over the experimental period. Microarray analysis showed that PF modulated the expression of genes specifically linked to nuclear factor (NF)-κB, resulting in downregulation of a number of genes in this pathway. These findings were further confirmed by real-time PCR of selected dysregulated genes as well as reduced expression of IL-6 and IL-8 proteins following PF treatment. The results arising from this study provide evidence that PF alters the inflammatory responses in intestinal epithelial cells through modulation of the NF-κB pathway. [ABSTRACT FROM AUTHOR]

The Crohn's disease (CD) exclusion diet (CDED) plus partial enteral nutrition (PEN) and exclusive enteral nutrition (EEN) both induce remission in pediatric CD. CDED+PEN is better tolerated and able to sustain remission. We characterized the changes in fecal metabolites induced by CDED+PEN and EEN and their relationship with remission. A total of 216 fecal metabolites were measured in 80 fecal samples at week (W) 0, W6, and W12, of children with mild to moderate CD in a prospective randomized trial comparing CDED+PEN vs EEN. The metabolites were measured using liquid chromatography coupled to mass spectrometry. Metagenome Kyoto Encyclopedia of Genes and Genomes Orthology analysis was performed to investigate the differential functional gene abundance involved in specific metabolic pathways. Data were analyzed according to clinical outcome of remission (W6_rem), no remission (W6_nr), sustained remission (W12_sr), and nonsustained (W12_nsr) remission. A decrease in kynurenine and succinate synthesis and an increase in N -α-acetyl-arginine characterized CDED+PEN W6_rem, whereas changes in lipid metabolism characterized EEN W6_rem, especially reflected by lower levels in ceramides. In contrast, fecal metabolites in EEN W6_nr were comparable to baseline/W0 samples. CDED+PEN W6_rem children maintained metabolome changes through W12. In contrast, W12_nsr children in the EEN group, who resumed a free diet after week 6, did not. The metabolome of CDED+PEN differed from EEN in the purine, pyrimidine, and sphingolipid pathways. A significant differential abundance in several genes involved in these pathways was detected. CDED+PEN– and EEN-induced remission are associated with significant changes in inflammatory bowel disease–associated metabolites such as kynurenine, ceramides, amino acids, and others. Sustained remission with CDED+PEN, but not EEN, was associated with persistent changes in metabolites. Clinicaltrials.gov , Number NCT01728870. [Display omitted] Precis Crohn's disease exclusion diet plus partial enteral nutrition– and exclusive enteral nutrition–induced remission in pediatric Crohn's disease exhibited unique metabolome profiles. Dietary nonresponders showed metabolite profiles similar to baseline. Exposure to free diet led to return to baseline metabolomic profile. [ABSTRACT FROM AUTHOR]

Software routers are becoming popular building blocks of software defined networking, due to their low cost and flexibility. Netmap is a platform that allows packet processing with high throughputs using standard computing hardware. The algorithm for energy‐efficient network processing based on netmap platform, named energy‐efficient netmap (EEN) is proposed and evaluated. EEN saves the energy by minimising the number of active cores needed to handle the given traffic load. Appreciable energy savings that can be achieved by the proposed algorithm is demonstrated. [ABSTRACT FROM AUTHOR]

Highlights: [•] Levels of EEN expression paralleled with the rate of cell proliferation. [•] EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. [•] EEN regulated the activity of IGF-1-Akt/mTOR pathway. [•] EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic, autoimmune disorder of the gastrointestinal tract with numerous genetic and environmental risk factors. Patients with Crohn's disease (CD) or ulcerative colitis (UC) often demonstrate marked disruptions of their gut microbiome. The intestinal microbiota is strongly influenced by diet. The association between the increasing incidence of IBD worldwide and increased consumption of a westernized diet suggests host nutrition may influence the progression or treatment of IBD via the microbiome. Several nutritional therapies have been studied for the treatment of CD and UC. While their mechanisms of action are only partially understood, existing studies do suggest that diet-driven changes in microbial composition and function underlie the diverse mechanisms of nutritional therapy. Despite existing therapies for IBD focusing heavily on immune suppression, nutrition is an important treatment option due to its superior safety profile, potentially low cost, and benefits for growth and development. These benefits are increasingly important to patients. In this review, we will describe the clinical efficacy of the different nutritional therapies that have been described for the treatment of CD and UC. We will also describe the effects of each nutritional therapy on the gut microbiome and summarize the strength of the literature with recommendations for the practicing clinician. [ABSTRACT FROM AUTHOR]