Jessica Connors

The Impact of Exclusive Enteral Nutrition (EEN) on the Gut Microbiome in Crohn’s Disease: A Review

Crohn’s disease (CD), a form of inflammatory bowel disease (IBD), is thought to arise from a complex interaction of genetics, the gut microbiome, and environmental factors, such as diet. There is clear evidence that dietary intervention is successful in the treatment of CD—exclusive enteral nutrition (EEN) is able to induce remission in up to 80% of CD patients. While the mechanism of action of EEN is not clear, EEN is known to cause profound changes in the gut microbiome. Understanding how EEN modifies the gut microbiome to induce remission could provide insight into CD etiopathogenesis and aid the development of microbiome-targeted interventions to guide ongoing dietary therapy to sustain remission. This review includes current literature on changes in composition and function of the gut microbiome associated with EEN treatment in CD patients.

Exclusive Enteral Nutrition Therapy in Paediatric Crohn’s Disease Results in Long-term Avoidance of Corticosteroids: Results of a Propensity-score Matched Cohort Analysis

Background and Aims Exclusive enteral nutrition [EEN] is recommended as a first-line induction therapy for paediatric Crohns 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 Crohns 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.

169 Assessment of Community Structure and Predictive Functional Profiling of the Mucosa-Associated Microbiome Implicates Alterations in Benzoate Metabolism in ‘de novo’ IBD After Pouch-Surgery and in Treatment-Naïve Pediatric IBD

of patients were identified: those developing early ER (N=12) and patients without ER (N=18) (Figure 1). Before surgery, a reduction of the Lachnospiraceae family (p=0.05) and Clostridium XVIII genus (p=0.032) was seen in the predominant microbiota of patients developing early postoperative ER whereas 3 members of Clostridium XIVa genus (p=0.073), Veillonellaceae family (p=0.028) and Bifidobacterium genus (p=0.01) were higher in patients with ER compared to patients without ER. A score combining these five bacterial risk factors was calculated and showed an area under the curve of 0.87 (95% CI, 0.76–0.99). The occurrence of two or more risk factors had a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 56%, 60% and 100% respectively. At the time of postoperative endoscopy, we observed an overrepresentation of Lactobacillus genus (p=0.003) and Ruminococcus gauvreauii (p=0.01) in the patients with ER. Conclusions: An overrepresentation of Clostridium XIVa spp., Veillonellaceae, Bifidobacteria and a lower abundance of Lachnospiraceae and Clostridium XVIII spp. in the predominant profile of preoperative fecal samples is associated with a higher risk to develop postoperative ER following ileocaecal resection. At the time of postoperative endoscopy, the predominant microbiota from patients with ER also differs from patients without recurrence, with as most prominent players lactobacilli and R. gauvreauii.

Mo1811 Clinical Remission Induced by Exclusive Enteral Nutrition (EEN) in Pediatric Crohn's Disease Is Associated With Microbiome Metabolic Changes Toward Increased Xenobiotic Biodegradation and Metabolism

esis of IBD, both Crohns disease (CD) and ulcerative colitis (UC), is not well known. Most studies of human gut microbiota rely on the non-invasive collection of stool samples. However, the analysis of the fecal microbiota may not reflect the role of the mucosa-associated microbes which live in close proximity to the intestinal epithelium and that are in contact with the cells of the innate immune system directly involved in the inflammatory response. The aim of this study was to investigate the genotypes of Bacteroidetes microbiota from colon biopsies of IBD patients and to determine their relationship with the endoscopic activity of the disease. Methods: A prospective case-control study was designed. Colon biopsies from consecutive IBD patients and healthy controls (HC) (healthy subjects undergoing colonoscopy for colon cancer screening and having a healthy colon mucosa) were included. Inactive UC was defined as a Mayo endoscopic subscore of 0. Inactive CD was defined as a SES-CD score ≤ 2. Microbiota was characterized by using a restriction fragment length polymorphism (RFLP) analysis on PCR products targeting the 16SrRNA genes of Bacteroidetes digested with HinfI, PciI, DpnII and AciI. Results are shown as percentages. Results: 29 consecutive IBD patients (22 UC and 7 CD) and 15 HC were included. 8 patients presented with inactive UC (iUC) and 14 with active UC (aUC). All 7 CD patients presented with endoscopic activity (aCD). A total of 7 genotypes of Bacteroidetes called N1 and C1-C6 (of which N1 genotype is probably a strain of Bacteroides dorei and C1, and maybe C2, strains of B. vulgatus) were detected in all the biopsy samples analyzed. The number of genotypes present in biopsies from IBD patients was higher than that in HC, in whom only the N1 (66%) and C1 (34%) genotypes appear. While the presence of N1 genotypes was relatively constant in patients with active and inactive IBD, the percentage of C1 genotype in patients with aUC and aCD were very low (<5%) compared to controls. The C4 genotype never appeared in control samples and it was present in only 2% of iUC biopsies, whereas it was present in 15% and 16% of patients with aUC and aCD respectively. The C2, C5 y C6 genotypes appeared sporadically in biopsies of IBD with percentages of 1% in iUC (C2), 3% in aUC and 1% in aCD (C5), and 1% in iUC and aCD (C6), but never in HC. Conclusions: Bacteroidetes genotypes in colon biopsies differ between IBD patients and HC. These genotypes, and especially the C4 genotype, are highly specific for active IBD and further studies on their role on IBD pathogenesis are required.