Research gaps in diet and nutrition in inflammatory bowel disease. A topical review by D-ECCO Working Group (Dietitians of ECCO)

Although the current doctrine of IBD pathogenesis proposes an interaction between environmental factors with gut microbiota in genetically-susceptible individuals, dietary exposures have attracted recent interest and are, at least in part, likely to explain the rapid rise in disease incidence and prevalence. The D-ECCO working group along with other ECCO experts with expertise in nutrition, microbiology, physiology and medicine reviewed the evidence investigating the role of diet and nutritional therapy in the onset, perpetuation and management of IBD. A narrative topical review is presented where evidence pertinent to the topic is summarized collectively under three main thematic domains: i) the role of diet as an environmental factor in IBD aetiology; ii) the role of diet as induction and maintenance therapy in IBD; and iii) assessment of nutritional status and supportive nutritional therapy in IBD. A summary of research gaps for each of these thematic domains is proposed which is anticipated to be agenda setting for future research in the area of diet and nutrition in IBD

Nutrition in Pediatric Inflammatory Bowel Disease: A Position Paper on Behalf of the Porto Inflammatory Bowel Disease Group of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition

Background and Aims:A growing body of evidence supports the need for detailed attention to nutrition and diet in children with inflammatory bowel disease (IBD). We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of pediatric IBD patients.Methods:A group of 20 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to Nutrition Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a systematic review of the literature.Results:A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment;macronutrients needs;trace elements, minerals, and vitamins;nutrition as a primary therapy of pediatric IBD;probiotics and prebiotics;specific dietary restrictions;and dietary compounds and the risk of IBD.Conclusions:This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD

Successful dietary therapy in paediatric Crohn’s disease is associated with shifts in bacterial dysbiosis and inflammatory metabotype towards healthy controls

Background and aims: Nutritional therapy with the Crohn’s Disease Exclusion Diet + Partial Enteral Nutrition [CDED+PEN] or Exclusive Enteral Nutrition [EEN] induces remission and reduces inflammation in mild-to-moderate paediatric Crohn’s disease [CD]. We aimed to assess if reaching remission with nutritional therapy is mediated by correcting compositional or functional dysbiosis. Methods: We assessed metagenome sequences, short chain fatty acids [SCFA] and bile acids [BA] in 54 paediatric CD patients reaching remission after nutritional therapy [with CDED + PEN or EEN] [NCT01728870], compared to 26 paediatric healthy controls. Results: Successful dietary therapy decreased the relative abundance of Proteobacteria and increased Firmicutes towards healthy controls. CD patients possessed a mixture of two metabotypes [M1 and M2], whereas all healthy controls had metabotype M1. M1 was characterised by high Bacteroidetes and Firmicutes, low Proteobacteria, and higher SCFA synthesis pathways, and M2 was associated with high Proteobacteria and genes involved in SCFA degradation. M1 contribution increased during diet: 48%, 63%, up to 74% [Weeks 0, 6, 12, respectively.]. By Week 12, genera from Proteobacteria reached relative abundance levels of healthy controls with the exception of E. coli. Despite an increase in SCFA synthesis pathways, remission was not associated with increased SCFAs. Primary BA decreased with EEN but not with CDED+PEN, and secondary BA did not change during diet. Conclusion: Successful dietary therapy induced correction of both compositional and functional dysbiosis. However, 12 weeks of diet was not enough to achieve complete correction of dysbiosis. Our data suggests that composition and metabotype are important and change quickly during the early clinical response to dietary intervention. Correction of dysbiosis may therefore be an important future treatment goal for CD

Sustained Diet-Induced Remission in Pediatric Crohn's Disease Is Associated With Kynurenine and Serotonin Pathways

BACKGROUND: Both the Crohn's disease exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) can induce remission in mild-to-moderate pediatric Crohn's disease and are associated with a marked decrease in fecal kynurenine levels. This suggests a link between clinical outcome of dietary therapy and changes in tryptophan metabolism pathways. Here, we characterize the changes in several fecal tryptophan metabolites induced by CDED+PEN or EEN and their association with remission. METHODS: A total of 21 tryptophan metabolites were quantified in fecal samples from a 12-week prospective randomized trial with CDED+PEN or EEN for induction of remission in mild to moderate pediatric Crohn's disease. Tryptophan metabolites at week 0 (W0), W6, and W12 of 73 samples were quantitatively measured by liquid chromatography coupled with triple quadrupole mass spectrometry, and data were analyzed according to clinical groups of baselines (W0), induced remission at W6, no remission, sustained remission at W12, and nonsustained remission. RESULTS: Reduction in components of the kynurenine pathway, such as kynurenine and quinolinic acid, were strongly associated with induced remission with both CDED+PEN and EEN, which were maintained in sustained remission. Specific serotonin pathway metabolites, such as melatonin, N-acetylserotonin, and 5-OH-tryptophan, were significantly increased in fecal samples from patients maintaining remission at W12 with both CDED+PEN and EEN. Importantly, in samples from patients failing to sustain remission, no changes were observed. Remission induction with EEN differs from CDED+PEN, particularly the moderate effects on indole pathway metabolites. The ratios of kynurenine and melatonin and quinolinic acid and melatonin perform well as markers for sustained remission. CONCLUSIONS: The reduction in specific kynurenine pathway compounds and the increase in serotonin pathway compounds are associated with diet-induced and sustained remission. Further studies are warranted to assess causality and the association of these metabolites with specific diet and lifestyle factors, affecting sustained clinical remission

Dietary Therapies Induce Rapid Response and Remission in Pediatric Patients With Active Crohn's Disease

Background & Aims: Dietary therapies based on exclusion of usual dietary elements induce remission in children with Crohn's disease (CD), whereas re-exposure induces rebound inflammation. We investigated whether a short trial of dietary therapy, to identify patients with and without a rapid response or remission on the diet (DiRe), can be used to predict success or failure of long-term dietary therapy. Methods: We collected data from the multicenter randomized trial of the CD exclusion diet (CDED). We analyzed data from 73 children with mild to moderate CD (mean age, 14.2 ± 2.7 y) randomly assigned to groups given either exclusive enteral nutrition (EEN, n = 34) or the CDED with 50% (partial) enteral nutrition (n = 39). Patients were examined at baseline and at weeks 3 and 6 of the diet. Remission was defined as CD activity index scores below 10 and response was defined as a decrease in score of 12.5 points or clinical remission. Inflammation was assessed by measurement of C-reactive protein. Results: At week 3 of the diet, 82% of patients in the CDED group and 85% of patients in the EEN group had a DiRe. Median serum levels of C-reactive protein had decreased from 24 mg/L at baseline to 5.0 mg/L at week 3 (P < .001). Among the 49 patients in remission at week 6, 46 patients (94%) had a DiRe and 81% were in clinical remission by week 3. In multivariable analysis, remission at week 3 increased odds of remission by week 6 (odds ratio, 6.37; 95% CI, 1.6–25; P = .008) whereas poor compliance reduced odds of remission at week 6 (odds ratio, 0.75; 95% CI, 0.012–0.46; P = .006). Conclusions: For pediatric patients with active CD, dietary therapies (CDED and EEN) induce a rapid clinical response (by week 3). Identification of patients with and without a rapid response to diet might help identify those who, with compliance, will be in clinical remission by week 6 of the diet. ClinicalTrials.gov no: NCT0172887

Research gaps in diet and nutrition in inflammatory bowel disease. A topical review by D-ECCO Working Group (Dietitians of ECCO)

Although the current doctrine of IBD pathogenesis proposes an interaction between environmental factors and gut microbiota in genetically susceptible individuals, dietary exposures have attracted recent interest and are, at least in part, likely to explain the rapid rise in disease incidence and prevalence. The D-ECCO working group along with other ECCO experts with expertise in nutrition, microbiology, physiology, and medicine reviewed the evidence investigating the role of diet and nutritional therapy in the onset, perpetuation, and management of IBD. A narrative topical review is presented where evidence pertinent to the topic is summarised collectively under three main thematic domains: i] the role of diet as an environmental factor in IBD aetiology; ii] the role of diet as induction and maintenance therapy in IBD; and iii] assessment of nutritional status and supportive nutritional therapy in IBD. A summary of research gaps for each of these thematic domains is proposed, which is anticipated to be agenda-setting for future research in the area of diet and nutrition in IBD

Metabolome Changes With Diet-Induced Remission in Pediatric Crohn's Disease

Background & Aims: 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. Methods: 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. Results: 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. Conclusion: 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

Perioperative dietary therapy in inflammatory bowel disease. Journal of Crohn and Colitis.

Adamina M, Gerasimidis K, Sigall-Boneh R, Zmora O, de Buck van Overstraeten A, Campmans-Kuijpers M, Ellul P, Katsanos K, Kotze P, Noor N, Schäfli-Thurnherr J, Vavricka S, Wall C, Wierdsma N, Yassin N, Lomer M. (2019) jjz160