Reverse-engineered exclusive enteral nutrition in pediatric Crohn's disease: A pilot trial.

BACKGROUND: In pediatric Crohn's disease (CD), commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing remission. This study aims to assess the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome. METHODS: A 4-week prospective trial assessed the impact of EEN with a whole-food smoothie on newly diagnosed mild-to-moderate active pediatric CD. The smoothie with a multivitamin were developed to meet age-appropriate nutritional requirements. Assessment over 4 weeks included Pediatric Crohn's Disease Activity Index (PCDAI), serum laboratories, fecal calprotectin (FCP), and stool collection for metagenomic shotgun sequencing and microbiota composition analysis. Clinical remission was defined as PCDAI ≤ 10 at week 4. RESULTS: Ten participants were enrolled with median age 14.5 years, and 8 completed the trial. Baseline mean PCDAI was 26.3 ± 9.1 and mean FCP 1149 ± 718 µg/g. At week 4, 80% of participants achieved clinical remission. FCP decreased by over half in 60% of participants, with FCP below 250 µg/g in 60% and below 100 µg/g in 40%. Microbiome analysis showed a significant increase in species richness over 4 weeks (p = 0.01). Compared to baseline, the relative abundance at week 2 and at week 4 was significantly increased for Bifidobacterium and Streptococcus and decreased for Blautia (p < 0.05 for all). CONCLUSION: A whole-food blended smoothie was effective for inducing clinical remission and decreasing FCP in pediatric CD similar to commercial EEN formulas. Further research may give insight into data-driven whole-food dietary approaches for CD management. CLINICALTRIALS: gov NCT03508193.

Do Histologic Features Help Predict Colectomy in Pediatric Patients Presenting With Acute Severe Colitis?

BACKGROUND: Multiple prior studies have looked at clinical and laboratory parameters in ulcerative colitis to predict prognosis, but individual histologic features of inflammation and their prognostic significance have not been well studied. The purpose of our study was to determine whether histologic features at presentation with acute severe colitis predict colectomy in pediatric patients. METHODS: Patients were identified retrospectively through the gastroenterology and pathology databases. Demographic information, duration of disease, laboratory data, endoscopic appearance at scope, and histologic features of inflammation were reviewed along with medical therapies. Patients who underwent surgery within 90 days of hospitalization were compared to those who did not. RESULTS: Fifty patients with acute severe colitis, defined as Pediatric Ulcerative Colitis Activity Index ≥65, were included. Sixteen patients had colectomies performed within 90 days of presentation. No statistically significant difference was found between the surgery and no-surgery groups for patient age, albumin, hemoglobin, or C-reactive protein, though hemoglobin trended toward significance, P = .05. The endoscopic Mayo score and histologic features of inflammation (architectural changes, chronic inflammation, eosinophils, neutrophils within the lamina propria, neutrophils in epithelium, crypt destruction, and ulceration) were similar between groups. CONCLUSION: In pediatric patients presenting for hospitalization with acute severe colitis, no histologic features of inflammation predicted colectomy within 90 days.

Dietary therapy for clostridium difficile colonization: A case series.

Clostridium difficile (C. difficile) is an important nosocomial pathogen in adults and children. Roughly 4-5% of non hospitalized healthy adults carry the organism in their intestinal flora while adults in long term care facilities have asymptomatic carriage rates estimated at 20-50%. C. difficile colonization results in a spectrum of clinical conditions from asymptomatic carrier state to fulminant colitis. Changes in the fecal microbiome are central in the development of C. difficile colonization and disease pathogenesis. C. difficile infection has been shown to be associated with reduced biodiversity of the gut microbiome and intestinal dysbiosis. With the importance of the intestinal microbiota in development of CDI and with the known impact of diet on the intestinal microbiota, we report the first known case of C. difficile colonization/recurrence successful treated by dietary modification.

Clinical and Fecal Microbial Changes With Diet Therapy in Active Inflammatory Bowel Disease.

GOAL: To determine the effect of the specific carbohydrate diet (SCD) on active inflammatory bowel disease (IBD). BACKGROUND: IBD is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Diet is a potential therapeutic option for IBD based on the hypothesis that changing the fecal dysbiosis could decrease intestinal inflammation. STUDY: Pediatric patients with mild to moderate IBD defined by pediatric Crohn's disease activity index (PCDAI 10-45) or pediatric ulcerative colitis activity index (PUCAI 10-65) were enrolled into a prospective study of the SCD. Patients started SCD with follow-up evaluations at 2, 4, 8, and 12 weeks. PCDAI/PUCAI, laboratory studies were assessed. RESULTS: Twelve patients, ages 10 to 17 years, were enrolled. Mean PCDAI decreased from 28.1±8.8 to 4.6±10.3 at 12 weeks. Mean PUCAI decreased from 28.3±23.1 to 6.7±11.6 at 12 weeks. Dietary therapy was ineffective for 2 patients while 2 individuals were unable to maintain the diet. Mean C-reactive protein decreased from 24.1±22.3 to 7.1±0.4 mg/L at 12 weeks in Seattle Cohort (nL<8.0 mg/L) and decreased from 20.7±10.9 to 4.8±4.5 mg/L at 12 weeks in Atlanta Cohort (nL<4.9 mg/L). Stool microbiome analysis showed a distinctive dysbiosis for each individual in most prediet microbiomes with significant changes in microbial composition after dietary change. CONCLUSIONS: SCD therapy in IBD is associated with clinical and laboratory improvements as well as concomitant changes in the fecal microbiome. Further prospective studies are required to fully assess the safety and efficacy of dietary therapy in patients with IBD.

Assuring Quality for Non-hospital-based Biologic Infusions in Pediatric Inflammatory Bowel Disease: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

The primary aim of this Clinical Report by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition is to provide formal guidance to pediatric gastroenterologists and clinicians, health systems, and insurance payers regarding home- and office-based infusions for biologic therapies in pediatric inflammatory bowel disease. Patients in North America are increasingly denied coverage by payers based on "place of service" codes at hospital-based infusion units where the treating clinicians primarily provide care. A task force with topic expertise generated 8 best practice recommendations to ensure quality of care for pediatric patients with inflammatory bowel disease receiving non-hospital-based biologic infusions. Pragmatic considerations discussed in this report include patient safety, pediatric-trained nurse availability, care coordination, patient-centeredness, shared liability, administrative support, clinical governance, and costs of care.

Children with Crohn's Disease Frequently Consume Select Food Additives.

OBJECTIVE: Certain food additives may promote the pathogenesis of Crohn's disease (CD), but thus far the evaluation of food additive exposures in humans has been limited. The objective of this study was to quantify food additive exposures in children with CD. METHODS: In a trial for bone health in CD, children were followed over 24 months with evaluation of disease characteristics, dietary intake, and body composition. At baseline, participants completed three 24-h dietary recalls. Foods were categorized, and the ingredient list for each item was evaluated for the presence of select food additives: polysorbate-80, carboxymethylcellulose, xanthan gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposures to these food additives was described for study participants and for food categories. RESULTS: At study baseline, 138 participants, mean age 14.2 ± 2.8 years, 95% having inactive or mild disease, were enrolled and dietary recalls were collected. A total of 1325 unique foods were recorded. Mean exposures per day for xanthan gum was 0.96 ± 0.72, carrageenan 0.58 ± 0.63, maltodextrin 0.95 ± 0.77, and soy lecithin 0.90 ± 0.74. The other additives had less than 0.1 exposures per day. For the 8 examined food additives, participants were exposed to a mean (SD) of 3.6 ± 2.1 total additives per recall day and a mean (SD) of 2.4 ± 1.0 different additives per day. CONCLUSION: Children with CD frequently consume food additives, and the impact on disease course needs further study.

Nutritional Adequacy of the Specific Carbohydrate Diet in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: The specific carbohydrate diet (SCD) is an exclusion diet used as a therapy in inflammatory bowel disease. The aim of this study was to evaluate the nutritional adequacy of the SCD. METHODS: Prospective dietary data for 12 weeks were analyzed for pediatric patients on the SCD. Intake of 20 key nutrients was compared to dietary recommended intake levels and nutrient intake data from similarly aged children from The National Health and Nutrition Examination Survey National Youth Fitness Survey in 2012. RESULTS: Nine patients enrolled, with 8 patients completing the study. Six of 8 individuals completing the study had gained weight, 1 individual had weight loss, and 1 had no change in weight. Energy intake was significantly greater than 100% of the recommended daily allowance (RDA)/adequate intake for 64% of daily intakes completed for this study. The majority of participants' daily intakes met or exceeded the RDA for vitamins B2, B3, B5, B6, B7, B12, C, A, and E. One hundred percent of participants' intakes were below the RDA for vitamin D. Seventy-five percent of daily intakes were less than the RDA for calcium. The upper limit was met or exceeded for magnesium in 42% of daily intakes. Average vitamin A intake was significantly greater than the upper limit (P = 0.01). CONCLUSIONS: Nutrient intake of pediatric inflammatory bowel disease patients on the SCD was adequate when compared with a healthy peer reference population, but adequacy was variable when compared with the dietary recommended intakes. Close monitoring with a multidisciplinary team for patients using the SCD as an alternative or adjunct therapy is recommend to ensure positive outcomes for overall patient health.

Lack of Mucosal Healing From Modified Specific Carbohydrate Diet in Pediatric Patients With Crohn Disease.

Exclusive enteral nutrition is effective in pediatric Crohn disease but challenging as maintenance therapy. There is interest in food-based therapies such as the specific carbohydrate diet (SCD) but paucity of data on efficacy and effect on mucosal healing, an evolving target of IBD therapy. We conducted a retrospective review of the mucosal healing effect of the SCD in pediatric Crohn disease (CD). The endoscopic findings for children younger than 18 years with CD treated exclusively with the SCD or modified SCD (mSCD; SCD + addition of "illegal foods") were reviewed before and after the diet. Ileocolonoscopic examinations were scored according to the Simple Endoscopic Score for CD and findings on upper endoscopy were described. Seven subjects were identified, all on mSCD. The average age at starting the SCD was 11 ±â€Š3.4 years and median duration of SCD/mSCD therapy was 26 months. All subjects reported no active symptoms before repeat endoscopic evaluation on mSCD, the majority had consistently normal C-reactive protein, albumin and hematocrit assessments, and mildly elevated fecal calprotectin (>50 µg/g, median 201, range 65-312) at any point within 3 months before the repeat endoscopy. One patient showed complete ileocolonic healing but persistent upper gastrointestinal tract ulceration. Complete macroscopic mucosal healing of both the ileocolon and upper gastrointestinal tract was not seen in any patient.

Nutritional Therapy in Very Early-Onset Inflammatory Bowel Disease: A Case Report.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract caused by a dysregulated immune response to the fecal microbiota. Very early-onset inflammatory bowel disease (VEO-IBD) refers to a subgroup of pediatric patients with IBD diagnosed before 6 years of age. This subgroup is often characterized by increased severity, aggressive progression, strong family history of IBD, and often poor response to conventional treatments. Nutritional therapies have been utilized to treat IBD, but their role in VEO-IBD is unclear. Disease behavior in VEO-IBD is often different from disease in adolescents and adults, as it is often restricted to the colon and refractory to standard medical therapies. Up to 25% of VEO-IBD patients have an identified underlying immunodeficiency, which may impact response to therapy. While specific mutations in interleukin 10 (IL-10), the IL-10 receptor (IL-10R), and mutations in NCF2, XIAP, LRBA, and TTC7 have been identified in VEO-IBD, polymorphisms in these genes are also associated with increased risk of developing IBD in adolescence or adulthood. We describe two cases in which infants presenting with VEO-IBD achieved clinical remission using exclusive enteral nutrition, a formula-based diet which has been shown to induce remission in older children with active Crohn's disease.

Ustekinumab in Pediatric Crohn Disease Patients.

OBJECTIVES: We describe the use of ustekinumab for 4 patients with pediatric Crohn disease treated at the Seattle Children's Hospital Inflammatory Bowel Disease Center. METHODS: A retrospective chart review was done to identify patients' clinical data, disease phenotype, treatment history, and laboratory and growth parameters before treatment with ustekinumab and at last follow-up. Adverse events while on ustekinumab were also recorded. RESULTS: Four adolescent patients with Crohn disease at our center received ustekinumab. All had previously received corticosteroids, methotrexate, azathioprine/6-mercaptopurine, and both infliximab and adalimumab. Patients had varying disease phenotypes. Ages at ustekinumab initiation were 12, 13, 16, and 17 years. Weight ranged from 40.5 to 57.8 kg, mean 49.5 kg. Two patients showed clinical response and remain on ustekinumab. Two patients discontinued therapy because of continued symptoms and disease complications and required multiple hospitalizations. CONCLUSIONS: Ustekinumab was used in 4 children with pediatric Crohn disease with 2 of 4 patients showing clinical response (1 with persistently elevated C-reactive protein). A prospective study is needed to define its efficacy, safety, and placement in managing pediatric Crohn disease in the future.

Precolectomy Therapy Does Not Alter Histologic Findings Distribution in Resected Colon in Pediatric Ulcerative Colitis.

OBJECTIVES: Medically intractable pediatric ulcerative colitis can lead to colectomy after which patients commonly receive an ileoanal pouch. Postoperative complications are more common in patients with Crohn disease, a diagnosis that may be rendered after the colectomy specimen is examined. Because most children are likely to be exposed to medications before colectomy, we sought to examine whether such exposure influences the distribution of the inflammation within the resected colon and therefore potentially raise questions about the diagnosis accuracy. METHODS: We conducted a retrospective cohort study of 32 pediatric ulcerative colitis cases undergoing colectomy from 2007 to 2014 for clinical data and precolectomy treatment history. The resected colon histology was reviewed independently by 2 blinded pathologists. The acute/active inflammation was scored using the modified Riley score for 3 colonic segments (proximal, transverse, and distal colon) for each patient. Linear mixed-effects models were used to evaluate possible association between acute/active inflammation scores at various sites and medication use. RESULTS: Twelve cases (38%) showed decreasing acute inflammation score distally to proximally, 8 (25%) had increasing scores, and 12 cases showed no change. Patients were most commonly exposed to corticosteroids, followed by anti-tumor necrosis factor antibodies. There was no statistically or clinically significant change in the histologic scores across the colonic segments of the resected colon in association with exposure to any specific medication or combination of medications, sex, age at diagnosis and surgery, or duration of disease. CONCLUSIONS: Precolectomy therapy does not seem to influence the distribution of inflammation within the resected colon.

Patients Perceive Clinical Benefit with the Specific Carbohydrate Diet for Inflammatory Bowel Disease.

BACKGROUND: Recent studies suggest that dietary therapy may be effective for patients with inflammatory bowel disease (IBD), but limited published data exist on the usage and efficacy of dietary therapy. AIM: To evaluate the perspective of IBD patients using the specific carbohydrate diet (SCD). METHODS: An anonymous online survey was conducted using REDCap, a Web-based survey tool. Survey links were sent to known Web sites as well as support groups in an attempt to characterize patient utilization of the SCD and perception of efficacy of the SCD. RESULTS: There were 417 respondents of the online survey on the SCD with IBD. Mean age for individuals on the SCD was 34.9 ± 16.4 years. Seventy percent were female. Forty-seven percent had Crohn's disease, 43 % had ulcerative colitis, and 10 % had indeterminate colitis. Individuals perceived clinical improvement on the SCD. Four percent reported clinical remission prior to the SCD, while 33 % reported remission at 2 months after initiation of the SCD, and 42 % at both 6 and 12 months. For those reporting clinical remission, 13 % reported time to achieve remission of less than 2 weeks, 17 % reported 2 weeks to a month, 36 % reported 1-3 months, and 34 % reported greater than 3 months. For individuals who reported reaching remission, 47 % of individuals reported associated improvement in abnormal laboratory values. CONCLUSIONS: The SCD is utilized by many patients as a primary and adjunct therapy for IBD. Most patients perceive clinical benefit to use of the SCD.

Fecal microbial transplant via nasogastric tube for active pediatric ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory disease of the large intestine, is characterized by a dysregulated immune reaction. UC is associated with fecal dysbiosis. Human and animal studies support the fact that the gastrointestinal microbiome may trigger the intestinal immune response, resulting in UC. Fecal microbial transplantation (FMT), by changing the gastrointestinal microbiome of patients with UC, may be a therapeutic option. METHODS: Four patients with moderate symptoms defined by the Pediatric Ulcerative Colitis Activity Index were enrolled in a prospective, open-label study of FMT via nasogastric tube in pediatric UC (US Food and Drug Administration IND 14942). After the donor and patient evaluation, patients received FMT with follow-up evaluations at 2, 6, and 12 weeks after transplantation. Study subjects were maintained on their pretransplant medications. The Pediatric Ulcerative Colitis Activity Index score, C-reactive protein, and stool calprotectin were completed during each study visit. RESULTS: Four patients with UC were enrolled (all boys). Ages ranged from 13 to 16 years. Patients tolerated FMT without adverse effects. None of the patients clinically improved with FMT, nor were there any significant changes in stool calprotectin or laboratory values, including C-reactive protein, albumin, and hematocrit. Three individuals received additional standard medical therapies before the end of the study. CONCLUSIONS: This study, although showing that single-dose FMT via nasogastric tube is well tolerated in active pediatric UC, did not show any clinical or laboratory benefit.

Fecal microbiota transplantation via nasogastric tube for recurrent clostridium difficile infection in pediatric patients.

Fecal microbiota transplantation (FMT) is a safe and effective therapy for adults with recurrent Clostridium difficile colitis, but data regarding FMT in children are limited and focus on colonoscopic administration of FMT. We present 10 consecutive children who received FMT via nasogastric tube for treatment of recurrent C difficile infection. Median age was 5.4 years, and 30% were receiving simultaneous immunosuppression. Median follow-up was 44 days, and 90% of patients resolved their C difficile infection; one patient relapsed 2 months later after receiving antibiotics. FMT via nasogastric tube appears safe, well tolerated, and effective in treating pediatric recurrent C difficile colitis.

Nutritional therapy in pediatric Crohn disease: the specific carbohydrate diet.

OBJECTIVES: Crohn disease is characterized by chronic intestinal inflammation in the absence of a recognized etiology. Nutritional therapy in the form of exclusive enteral nutrition (EEN) has an established role within pediatric Crohn disease. Following exclusive enteral nutrition's success, many dietary therapies focusing on the elimination of specific complex carbohydrates have been anecdotally reported to be successful. METHODS: Many of these therapies have not been evaluated scientifically; therefore, we reviewed the medical records of our patients with Crohn disease on the specific carbohydrate diet (SCD). RESULTS: Seven children with Crohn disease receiving the SCD and no immunosuppressive medications were retrospectively evaluated. Duration of the dietary therapy ranged from 5 to 30 months, with an average of 14.6±10.8 months. Although the exact time of symptom resolution could not be determined through chart review, all symptoms were notably resolved at a routine clinic visit 3 months after initiating the diet. Each patient's laboratory indices, including serum albumin, C-reactive protein, hematocrit, and stool calprotectin, either normalized or significantly, improved during follow-up clinic visits. CONCLUSIONS: This chart review suggests that the SCD and other low complex carbohydrate diets may be possible therapeutic options for pediatric Crohn disease. Further prospective studies are required to fully assess the safety and efficacy of the SCD, or any other low complex SCDs in pediatric patients with Crohn disease.

Imaging and endoscopic tools in pediatric inflammatory bowel disease: What's new?

Pediatric inflammatory bowel disease (IBD) is a chronic inflammatory disorder, with increasing incidence and prevalence worldwide. There have been recent advances in imaging and endoscopic technology for disease diagnosis, treatment, and monitoring. Intestinal ultrasound, including transabdominal, transperineal, and endoscopic, has been emerging for the assessment of transmural bowel inflammation and disease complications (e.g., fistula, abscess). Aside from surgery, IBD-related intestinal strictures now have endoscopic treatment options including through-the-scope balloon dilatation, injection, and needle knife stricturotomy and new evaluation tools such as endoscopic functional lumen imaging probe. Unsedated transnasal endoscopy may have a role in patients with upper gastrointestinal Crohn's disease or those with IBD with new upper gastrointestinal symptoms. Improvements to dysplasia screening in pediatric patients with longstanding colonic disease or primary sclerosing cholangitis hold promise with the addition of virtual chromoendoscopy and ongoing research in the field of artificial intelligence-assisted endoscopic detection. Artificial intelligence and machine learning is a rapidly evolving field, with goals of further personalizing IBD diagnosis and treatment selection as well as prognostication. This review summarized these advancements, focusing on pediatric patients with IBD.

Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy.

BACKGROUND & AIMS: Homozygous loss of function mutations in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) cause severe infantile (very early onset) inflammatory bowel disease (IBD). Allogeneic hematopoietic stem cell transplantation (HSCT) was reported to induce sustained remission in 1 patient with IL-10R deficiency. We investigated heterogeneity among patients with very early onset IBD, its mechanisms, and the use of allogeneic HSCT to treat this disorder. METHODS: We analyzed 66 patients with early onset IBD (younger than 5 years of age) for mutations in the genes encoding IL-10, IL-10R1, and IL-10R2. IL-10R deficiency was confirmed by functional assays on patients' peripheral blood mononuclear cells (immunoblot and enzyme-linked immunosorbent assay analyses). We assessed the therapeutic effects of standardized allogeneic HSCT. RESULTS: Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency: 3 patients had mutations in IL-10, 5 had mutations in IL-10R1, and 8 had mutations in IL-10R2. Refractory colitis became manifest in all patients within the first 3 months of life and was associated with perianal disease (16 of 16 patients). Extraintestinal symptoms included folliculitis (11 of 16) and arthritis (4 of 16). Allogeneic HSCT was performed in 5 patients and induced sustained clinical remission with a median follow-up time of 2 years. In vitro experiments confirmed reconstitution of IL-10R-mediated signaling in all patients who received the transplant. CONCLUSIONS: We identified loss of function mutations in IL-10 and IL-10R in patients with very early onset IBD. These findings indicate that infantile IBD patients with perianal disease should be screened for IL-10 and IL-10R deficiency and that allogeneic HSCT can induce remission in those with IL-10R deficiency.