Effect of Exclusive Enteral Nutrition and Corticosteroid Induction Therapy on the Gut Microbiota of Pediatric Patients with Inflammatory Bowel Disease

Abstract

Introduction: Exclusive enteral nutrition (EEN) and corticosteroids (CS) are effective induction therapies for pediatric Crohn’s Disease (CD). CS are also therapy for ulcerative colitis (UC). Host–microbe interactions may be able to explain the effectiveness of these treatments. This is the first prospective study to longitudinally characterize compositional changes in the bacterial community structure of pediatric UC and CD patients receiving EEN or CS induction therapy. Methods: Patients with diagnoses of CD or UC were recruited from McMaster Children’s Hospital (Hamilton, Canada). Fecal samples were collected from participants aged 5–18 years old undergoing 8 weeks of induction therapy with EEN or CS. Fecal samples were submitted for 16S rRNA sequencing. The Shannon diversity index and the relative abundance of specific bacterial taxa were compared using a linear mixed model. Results: The clustering of microbiota was the highest between patients who achieved remission compared to patients still showing active disease (p = 0.029); this effect was independent of the diagnosis or treatment type. All patients showed a significant increase in Shannon diversity over the 8 weeks of treatment. By week 2, a significant difference was seen in Shannon diversity between patients who would go on to achieve remission and those who would not. Conclusion: The gut microbiota of pediatric UC and CD patients was most influenced by patients’ success or failure to achieve remission and was largely independent of the choice of treatment or disease type. Significant differences in Shannon diversity indices occurred as early as week 2 between patients who went on to achieve remission and those who continued to have active disease.

Nutritional Therapy Strategies in Pediatric Crohn’s Disease

“…Changes in fecal microbial composition induced by EEN or CDED + PEN have been linked with remission and sustained remission [ 3 , 100 , 141 , 142 ]. In an RCT, both CDED + PEN and EEN were effective in inducing remission by week 6 and showed similar taxa changes: a decrease in Actinobacteria and Proteobacteria and an increase in Clostridia [ 3 ].…”

Urinary Metabolites Enable Differential Diagnosis and Therapeutic Monitoring of Pediatric Inflammatory Bowel Disease

“…Since metabolic profiles, especially that of urine, tend to be strongly influenced by short-term changes in diet [ 36 ], one of the challenges in this study was to distinguish metabolites/nutrients associated with intake of EEN formula from changes in mucosal healing and gut microbiota metabolism with clinical remission. As expected, initiation of EEN therapy constitutes a major change in normal oral feeding patterns in children from baseline as it is composed of a standardized liquid formula providing total caloric and nutritional requirements for an 8-week period [ 22 ]. In our study, 72% ( n = 19) of recently diagnosed CD patients (including one UC patient) were prescribed EEN for the first time, and 68% ( n = 13) achieved full remission or partial treatment response (32%, n = 6) after 8 weeks.…”

“…The study enrolled children from 5 to 18 years old who had been diagnosed with IBD by endoscopy, histology and radiography at McMaster Children’s Hospital. Patients were included if they were admitted to hospital to be initiated on EEN therapy using Peptamen ® 1.5 (Nestlé Health Sciences, Bridgewater, NJ, USA) at 120% of their daily caloric needs, or intravenous CS (1 mg/kg/day methylprednisolone) for induction of IBD remission [ 22 ]. Patients were discharged home once full volumes of EEN feeds were achieved (<72 h upon admission), and other than formula, they were allowed to consume only clear fluids orally.…”

“…In this retrospective cohort study, the urine metabolome is characterized from a cohort of pediatric IBD patients who subsequently receive EEN or corticosteroid (CS) induction therapy. We recently demonstrated that changes in gut microbiome diversity is a key factor associated with mucosal healing and clinical remission, independent of treatment modality and IBD disease subtype [ 22 ]. In the present work, a panel of urinary metabolites are identified to differentiate pediatric CD from UC that is not feasible by conventional inflammatory biomarkers in stool and serum.…”

Advances in Nutritional Management of Pediatric Inflammatory Bowel Disease

“…They found no difference in the fecal microbiota between the 2 modalities of treatment when patients achieve clinical remission. i.e., while there is a significant difference in the fecal microbiota between patients with active disease versus those who achieved remission, the choice of treatment did not lead to a different microbiome in those who achieved clinical remission [ 8 ]. The study was limited by the small sample size.…”