Characterisation of Gut Microbial Taxonomy and Functionality using Next Generation Sequencing in Children with Crohn's Disease during Exclusive Enteral Nutrition. Crohn's in Childhood Research Association, (2013 - 2014)
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ABSTRACT:
PROVIDER: PRJEB18780 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR1776590_1.fastq.gz | Fastqsanger.gz | |||
| ERR1776590_2.fastq.gz | Fastqsanger.gz | |||
| ERR1776600_1.fastq.gz | Fastqsanger.gz | |||
| ERR1776600_2.fastq.gz | Fastqsanger.gz |
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Project description:Exclusive enteral nutrition modulates the faecal metagenome in paediatric Crohn’s disease not by enriching the abundance of presumably ‘beneficial’ commensals but by suppressing ‘dysbiotic’ bacteria
| PRJEB7576 | ENA
Project description: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.
| S-EPMC9059691 | biostudies-literature
Project description:BackgroundMany studies have examined the effects of exclusive enteral nutrition (EEN) in children with Crohn's disease (CD), but corticosteroids are considered a superior therapy and are frequently used in China. This meta-analysis aims to compare the efficacy of EEN with corticosteroids in treating pediatric CD.MethodsA comprehensive retrieval from medical databases, including PubMed, EMBASE, MEDLINE, Web of Science, Wanfang data, VIP and CNKI, was performed using the search terms "diet therapy", "exclusive enteral nutrition", "Crohn's disease", "inflammatory bowel diseases", "child" and "pediatrics" from January 1990 to April 2017.ResultsWe included 18 studies from 1329 identified sources in this meta-analysis. EEN was as effective as corticosteroids in inducing remission rate of children suffering from CD (OR?=?1.35; 95% CI 0.90, 2.10; P?=?0.14). Nevertheless, patients who received EEN were more likely to achieve both endoscopic mucosal healing (OR?=?5.24; 95% CI 2.06, 13.37; P?=?0.0005) and histological mucosal healing (OR?=?4.78; 95% CI 1.89, 12.08; P?=?0.0009) than those who received corticosteroids; the Pediatric Crohn's Disease Activity Index was lower [mean difference (MD)?=?- 3.67; 95% CI - 4.91, - 2.43] and weight gain was higher (MD?=?1.92; 95% CI 0.02, 3.83; P?=?0.05) in those patients who received EEN than in those who received corticosteroids. No difference was found in relapse rate (OR?=?0.57; 95% CI 0.25, 1.29; P?=?0.18), height for age or body mass index between the patients treated with EEN and corticosteroids at the 1-year end point.ConclusionsThis meta-analysis reveals that there is no significant difference between EEN and corticosteroids in the efficacy of inducing remission rate of CD in a pediatric population, but EEN is superior to corticosteroids in improving short-term mucosal inflammation and reducing the PCDAI index.
| S-EPMC6394648 | biostudies-literature
Project description:Background/aimsExclusive enteral nutrition (EEN), an established modality for pediatric Crohn's disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India.MethodsThis was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn's Disease Activity Index (CDAI), and clinical response (decline in CDAI > 70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response.ResultsThirty-one CD patients received EEN over median duration of 4 weeks (range, 2-6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260-320] vs. 240 [180-280], P= 0.001) and 8 weeks (baseline 290 [260-320] vs. 186 [160-240], P= 0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n = 4), B2 (n = 18) and B3 (n = 9) phenotypes were 50%, 78.8% and 100% respectively (log-rank test, P= 0.093). The response rates at 8 weeks with polymeric (n = 8) and semi-elemental diet (n = 23) were 75% and 82.6%% respectively (log-rank test, P= 0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002-1.017; P= 0.046) predicted response to EEN.ConclusionsEEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN.
| S-EPMC8322023 | biostudies-literature
Project description:ObjectivesExclusive enteral nutrition (EEN) is commonly used to treat pediatric Crohn's disease (CD). Meta-analysis of pediatric studies that have compared the effect of EEN with other treatments have shown that EEN induces remission in up to 80-85% of patients. We aimed to gain a comprehensive understanding of the effect of EEN on the microbiota of CD patients.MethodsWe used 16S rRNA gene and whole-genome high throughout sequencing to determine changes in the fecal microbiota of five CD children, before, during, and after EEN therapy and compared this with five healthy controls.ResultsThe microbial diversity observed in CD patients tended to be lower than that in controls (CD: 2.25±0.24, controls: 2.75±0.14, P=0.11). In all CD patients, dysbiosis was observed prior to therapy. EEN therapy had a positive effect in all patients, with 80% going into remission. In some patients, the positive effect diminished following the conclusion of EEN therapy. Significantly, the number of operational taxonomic units (OTU) decreased dramatically upon starting EEN and this corresponded with CD remission. Recurrence of CD corresponded with an increase in OTUs. Six families within the Firmicutes were found to correlate with disease activity during and following EEN therapy, a finding that was confirmed by whole-genome high throughput sequencing.ConclusionsOur results demonstrate that EEN leads to common and patient-specific alterations in the microbiota of CD patients, a number of which correlate with disease activity.
| S-EPMC4418409 | biostudies-literature
Project description:ObjectivesExploring associations between the gut microbiota and colonic inflammation and assessing sequential changes during exclusive enteral nutrition (EEN) may offer clues into the microbial origins of Crohn's disease (CD).MethodsFecal samples (n=117) were collected from 23 CD and 21 healthy children. From CD children fecal samples were collected before, during EEN, and when patients returned to their habitual diets. Microbiota composition and functional capacity were characterized using sequencing of the 16S rRNA gene and shotgun metagenomics.ResultsMicrobial diversity was lower in CD than controls before EEN (P=0.006); differences were observed in 36 genera, 141 operational taxonomic units (OTUs), and 44 oligotypes. During EEN, the microbial diversity of CD children further decreased, and the community structure became even more dissimilar than that of controls. Every 10 days on EEN, 0.6 genus diversity equivalents were lost; 34 genera decreased and one increased during EEN. Fecal calprotectin correlated with 35 OTUs, 14 of which accounted for 78% of its variation. OTUs that correlated positively or negatively with calprotectin decreased during EEN. The microbiota of CD patients had a broader functional capacity than healthy controls, but diversity decreased with EEN. Genes involved in membrane transport, sulfur reduction, and nutrient biosynthesis differed between patients and controls. The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN.ConclusionsDisease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.
| S-EPMC4697132 | biostudies-literature
Project description:MicroRNAs (miRNAs) have been shown to be important for the pathogenesis of Crohn's disease (CD). Exclusive enteral nutrition (EEN) is an effective therapy for inducing remission in CD. We aimed to investigate the alteration of miRNAs expression profile in the terminal ileal mucosa of CD patients before and after EEN. Twenty-five patients and ten healthy individuals were included. MiRNAs expression profile was firstly assessed using microarray technology and then validation was performed by qRT-PCR. The correlations between miRNAs and CD activity index (CDAI) score and serum C-reactive protein (CRP) level were also evaluated. Microarray analysis showed that mucosal miRNAs expression profile after EEN therapy was significantly changed compared with inflamed mucosa before treatment, and was most similar to the healthy one among all CD groups. Altered expressions of hsa-miR-192-5p, hsa-miR-423-3p, hsa-miR-99a-5p, hsa-miR-124-3p, hsa-miR-301a-5p, hsa-miR-495-5p, and hsa-let-7b-5p were confirmed by qRT-PCR. hsa-let-7b-5p was significantly correlated with serum CRP levels before and after EEN treatment (r = -0.518, p = 0.008, and r = -0.569, p = 0.003). Our study showed EEN induction therapy was associated with a trend for normalizing of the mucosal miRNAs expression profile, and expression of mucosal hsa-let-7b-5p was correlated with serum CRP level in patients with CD.
| S-EPMC4997431 | biostudies-literature
Project description:BackgroundThe gut microbiome is extensively involved in induction of remission in pediatric Crohn's disease (CD) patients by exclusive enteral nutrition (EEN). In this follow-up study of pediatric CD patients undergoing treatment with EEN, we employ machine learning models trained on baseline gut microbiome data to distinguish patients who achieved and sustained remission (SR) from those who did not achieve remission nor relapse (non-SR) by 24 weeks.MethodsA total of 139 fecal samples were obtained from 22 patients (8-15 years of age) for up to 96 weeks. Gut microbiome taxonomy was assessed by 16S rRNA gene sequencing, and functional capacity was assessed by metagenomic sequencing. We used standard metrics of diversity and taxonomy to quantify differences between SR and non-SR patients and to associate gut microbial shifts with fecal calprotectin (FCP), and disease severity as defined by weighted Pediatric Crohn's Disease Activity Index. We used microbial data sets in addition to clinical metadata in random forests (RFs) models to classify treatment response and predict FCP levels.ResultsMicrobial diversity did not change after EEN, but species richness was lower in low-FCP samples (<250 µg/g). An RF model using microbial abundances, species richness, and Paris disease classification was the best at classifying treatment response (area under the curve [AUC] = 0.9). KEGG Pathways also significantly classified treatment response with the addition of the same clinical data (AUC = 0.8). Top features of the RF model are consistent with previously identified IBD taxa, such as Ruminococcaceae and Ruminococcus gnavus.ConclusionsOur machine learning approach is able to distinguish SR and non-SR samples using baseline microbiome and clinical data.
| S-EPMC7301407 | biostudies-literature
Project description: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 registrationClinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).
| S-EPMC8642954 | biostudies-literature
Project description:Microarray analysis of HT-29 cells co-cultured with tumor necrosis factor (TNF-a) in the presence or absence of polymeric formula as used for Exclusive Enteral Nutrition (EEN) therapy. Results provide insights into the molecular mechanisms underlying the anti-inflammatory effect of polymeric formula on intestinal epithelium.
2015-12-04 | GSE69605 | GEO