Ghassan Wahbeh

Fecal Microbial Transplant Effect on Clinical Outcomes and Fecal Microbiome in Active Crohn’s disease

Background:Crohns disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbial transplant (FMT) is a potential therapeutic option for individuals with CD based on the hypothesis that changing the fecal dysbiosis could promote less intestinal inflammation. Methods:Nine patients, aged 12 to 19 years, with mild-to-moderate symptoms defined by Pediatric Crohns Disease Activity Index (PCDAI of 10–29) were enrolled into a prospective open-label study of FMT in CD (FDA IND 14942). Patients received FMT by nasogastric tube with follow-up evaluations at 2, 6, and 12 weeks. PCDAI, C-reactive protein, and fecal calprotectin were evaluated at each study visit. Results:All reported adverse events were graded as mild except for 1 individual who reported moderate abdominal pain after FMT. All adverse events were self-limiting. Metagenomic evaluation of stool microbiome indicated evidence of FMT engraftment in 7 of 9 patients. The mean PCDAI score improved with patients having a baseline of 19.7 ± 7.2, with improvement at 2 weeks to 6.4 ± 6.6 and at 6 weeks to 8.6 ± 4.9. Based on PCDAI, 7 of 9 patients were in remission at 2 weeks and 5 of 9 patients who did not receive additional medical therapy were in remission at 6 and 12 weeks. No or modest improvement was seen in patients who did not engraft or whose microbiome was most similar to their donor. Conclusions:This is the first study to demonstrate that FMT for CD may be a possible therapeutic option for CD. Further prospective studies are required to fully assess the safety and efficacy of the FMT in patients with CD.

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 nutritions 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 patients 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.

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.

Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations

Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and subspecialty providers.

Tolerability of curcumin in pediatric inflammatory bowel disease: a forced-dose titration study.

Background: Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation in the absence of a recognized etiology. The primary therapies are medications that possess anti-inflammatory or immunosuppressive effects. Given the high use of complementary alternative medicines in pediatric IBD, a prospective tolerability study of curcumin, an herbal therapy with known anti-inflammatory effects, was conducted to assess possible dosage in children with IBD. Methods: Prospectively, patients with Crohn disease or ulcerative colitis in remission or with mild disease (Pediatric Crohns Disease Activity Index [PCDAI] <30 or Pediatric Ulcerative Colitis Activity Index [PUCAI] score <34) were enrolled in a tolerability study. All patients received curcumin in addition to their standard therapy. Patients initially received 500 mg twice per day for 3 weeks. Using the forced-dose titration design, doses were increased up to 1 g twice per day at week 3 for a total of 3 weeks and then titrated again to 2 g twice per day at week 6 for 3 weeks. Validated measures of disease activity, using the PUCAI and PCDAI, and the Monitoring of Side Effect System score were obtained at weeks 3, 6, and 9. Results: All patients tolerated curcumin well, with the only symptom that was consistently reported during all 3 visits being an increase in gassiness, which occurred in only 2 patients. Three patients saw improvement in PUCAI/PCDAI score. Conclusions: This pilot study suggests that curcumin may be used as an adjunctive therapy for individuals seeking a combination of conventional medicine and alternative medicine.

Specific carbohydrate diet for pediatric inflammatory bowel disease in clinical practice within an academic IBD center

OBJECTIVE Despite dietary factors being implicated in the pathogenesis of inflammatory bowel disease (IBD), nutritional therapy, outside of exclusive enteral nutrition (EEN), has not had a defined role within the treatment paradigm of pediatric IBD within IBD centers. Based on emerging data, Seattle Childrens Hospital IBD Center has developed an integrated dietary program incorporating the specific carbohydrate diet (SCD) into its treatment paradigm. This treatment paradigm uses the SCD as primary therapy as well as adjunctive therapy for the treatment of IBD. The aim of this study was to evaluate the potential effects of the SCD on clinical outcomes and laboratory studies of pediatric patients with Crohns disease (CD) and ulcerative colitis (UC). METHODS In this retrospective study, we reviewed the medical records of patients with IBD on SCD. RESULTS We analyzed 26 children on the SCD: 20 with CD and 6 with UC. Duration of the dietary therapy ranged from 3 to 48 mo. In patients with active CD (Pediatric Crohns Disease activity index [PCDAI] >10), PCDAI dropped from 32.8 ± 13.2 at baseline to 20.8 ± 16.6 by 4 ± 2 wk, and to 8.8 ± 8.5 by 6 mo. The mean Pediatric Ulcerative Colitis Activity Index for patients with active UC decreased from a baseline of 28.3 ± 10.3 to 20.0 ± 17.3 at 4 ± 2 wk, to 18.3 ± 31.7 at 6 mo. CONCLUSION This retrospective review provides evidence that the SCD can be integrated into a tertiary care center and may improve clinical and laboratory parameters for pediatric patients with nonstructuring, nonpenetrating CD as well as UC. Further prospective studies are needed to fully assess the safety and efficacy of the SCD in pediatric patients with IBD.

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

ABSTRACT 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.

Collagenous gastritis, a new spectrum of disease in pediatric patients: two case reports

Collagenous gastritis is a rare gastrointestinal disorder characterized in pediatrics by abdominal pain and anemia. The literature divides collagenous gastritis into distinct pediatric-onset and adult-onset phenotypes. As opposed to pediatric form, the adult form is associated with collagenous colitis and presents clinically with voluminous non-bloody diarrhea. There are over 25 case reports of collagenous gastritis of which 10 are pediatric cases. We present two cases of pediatric onset collagenous gastritis: one with a classic pediatric presentation, the other with findings typical of adult-onset disease. This is the first report of the adult-onset phenotype collagenous gastritis in a pediatric patient.

Maternal microchimerism in pediatric inflammatory bowel disease

Inflammatory bowel disease (IBD) shares many immunologic and clinical characteristics with graft versus host disease caused by allogeneic T lymphocytes after hematopoietic cell transplantation. Since maternal cells are known to enter the fetal circulation in a high proportion of pregnancies, we hypothesized that maternal engraftment in the fetus results in immune sequelae that can lead to IBD. Method: The presence and extent of maternal microchimerism in tissues and blood samples from patients with Crohn’s, Ulcerative colitis (UC), and control groups were determined using kinetic Polymerase Chain Reaction (kPCR) to detect maternal- and patient-specific HLA types. In addition, fluorescent in situ hybridization (FISH) was employed to detect maternal cells in biopsies from patients with IBD. Results: Using kPCR, maternal microchimerism was observed in 9 of the 16 (56%) patients with IBD and 6 out of 15 of the control group (40%) (P=NS). Five of 10 Crohn’s patients had evidence of maternal microchimerism (50%) (P=NS). Four of 6 UC patients had evidence of maternal microchimerism in gut tissues (67%) (P=NS). There is no correlation between maternal michrochimerism and disease activity, disease location or granulomas in patients with IBD. Using FISH, 5 male Crohn’s and 5 male UC patient’s intestinal biopsies were analyzed for maternal microchimerism. No maternal cells were identified.

Gastric contents in pediatric patients following bone marrow transplantation

Background:  Graft versus host disease (GVHD) of the gut is thought to delay gastric emptying and so may increase the risk of aspirating retained contents while under anesthesia. Knowing that gastric emptying is delayed in patients with GVHD might lead one to choose to intubate the trachea for all patients with suspected GVHD, who present for diagnostic esophagogastricduodenoscopy (EGD). We are not aware of published data that gives specific guidance as to the need for intubation in the pediatric bone marrow or stem cell transplantation (BMT) population. This review was intended to evaluate the gastric contents (pH and volume) in this group of patients, to provide anesthesiologists with data that would inform their decisions about airway management for these patients.