Erica M. Weidler

Gastrointestinal Microbiome Signatures of Pediatric Patients With Irritable Bowel Syndrome

BACKGROUND & AIMS The intestinal microbiomes of healthy children and pediatric patients with irritable bowel syndrome (IBS) are not well defined. Studies in adults have indicated that the gastrointestinal microbiota could be involved in IBS. METHODS We analyzed 71 samples from 22 children with IBS (pediatric Rome III criteria) and 22 healthy children, ages 7-12 years, by 16S ribosomal RNA gene sequencing, with an average of 54,287 reads/stool sample (average 454 read length = 503 bases). Data were analyzed using phylogenetic-based clustering (Unifrac), or an operational taxonomic unit (OTU) approach using a supervised machine learning tool (randomForest). Most samples were also hybridized to a microarray that can detect 8741 bacterial taxa (16S rRNA PhyloChip). RESULTS Microbiomes associated with pediatric IBS were characterized by a significantly greater percentage of the class γ-proteobacteria (0.07% vs 0.89% of total bacteria, respectively; P < .05); 1 prominent component of this group was Haemophilus parainfluenzae. Differences highlighted by 454 sequencing were confirmed by high-resolution PhyloChip analysis. Using supervised learning techniques, we were able to classify different subtypes of IBS with a success rate of 98.5%, using limited sets of discriminant bacterial species. A novel Ruminococcus-like microbe was associated with IBS, indicating the potential utility of microbe discovery for gastrointestinal disorders. A greater frequency of pain correlated with an increased abundance of several bacterial taxa from the genus Alistipes. CONCLUSIONS Using 16S metagenomics by PhyloChip DNA hybridization and deep 454 pyrosequencing, we associated specific microbiome signatures with pediatric IBS. These findings indicate the important association between gastrointestinal microbes and IBS in children; these approaches might be used in diagnosis of functional bowel disorders in pediatric patients.

Creation and Initial Evaluation of a Stool Form Scale for Children

OBJECTIVE To develop a pediatric stool form rating scale and determine its interrater reliability, intrarater reliability, and agreement among pediatric gastroenterologists. STUDY DESIGN An ordinal stool scale with 5 categorical stool form types was created on the basis of the Bristol Stool Form Scale, and 32 color 2-dimensional stool photographs were shown to 14 pediatric gastroenterologists. Each gastroenterologist rated the stool form depicted in each photograph with the modified stool scale. Ten gastroenterologists agreed to rerate the stool form depicted in each photograph a minimum of 6 months after the first rating. RESULTS A total of 448 ratings were completed; 430 (94%) of all ratings were within at least 1 category type of the most common (modal) rating for each photograph. Eight (25%) stool photographs had complete agreement among all raters. Interrater and intrarater reliability was high with a single measure intraclass correlation of 0.85 (95% confidence interval: 0.78-0.91; P<.001) and 0.87 (95% confidence interval: 0.81-0.92; P<.001), respectively. CONCLUSION A modified pediatric Bristol Stool Form Scale provided a high degree of interrater reliability, intrarater reliability, and agreement among pediatric gastroenterologists.

Pain Symptoms and Stooling Patterns Do Not Drive Diagnostic Costs for Children With Functional Abdominal Pain and Irritable Bowel Syndrome in Primary or Tertiary Care

OBJECTIVE. The objectives of this study were to (1) compare the cost of medical evaluation for children with functional abdominal pain or irritable bowel syndrome brought to a pediatric gastroenterologist versus children who remained in the care of their pediatrician, (2) compare symptom characteristics for the children in primary versus tertiary care, and (3) examine if symptom characteristics predicted the cost of medical evaluation. METHODS. Eighty-nine children aged 7 to 10 years with functional abdominal pain or irritable bowel syndrome seen by a gastroenterologist (n = 46) or seen only by a pediatrician (n = 43) completed daily pain and stool diaries for 2 weeks. Mothers provided retrospective reports of their childrens symptoms in the previous year. Cost of medical evaluation was calculated via chart review of diagnostic tests and application of prices as if the patients were self-pay. RESULTS. Child-reported diary data reflected no significant group differences with respect to pain, interference with activities, or stool characteristics. In contrast, mothers of children evaluated by a gastroenterologist viewed their children as having higher maximum pain intensity in the previous year. Excluding endoscopy costs, cost of medical evaluation was fivefold higher for children evaluated by a gastroenterologist, with higher cost across blood work, stool studies, breath testing, and diagnostic imaging. Symptom characteristics did not predict cost of care for either group. CONCLUSIONS. Despite the lack of difference in symptom characteristics between children in primary and tertiary care, a notable differential in cost of evaluation exists in accordance with level of care. Symptom characteristics do not seem to drive diagnostic evaluation in either primary or tertiary care. Given the lack of differences in child-reported symptoms and the maternal perspective that children evaluated by a gastroenterologist had more severe pain, we speculate that parent perception of child symptoms may be a primary factor in seeking tertiary care.

The interpretation of Rome III criteria and method of assessment affect the irritable bowel syndrome classification of children.

Aliment Pharmacol Ther 2011; 33: 403–411

Subtypes of Irritable Bowel Syndrome in Children and Adolescents

BACKGROUND & AIMS Pharmacologic treatments for irritable bowel syndrome (IBS) and medical management of symptoms are increasingly based on IBS subtype, so it is important to accurately differentiate patients. Few studies have classified subtypes of pediatric IBS, and conclusions have been challenged by methodologic limitations. We performed a prospective study to investigate the distribution of IBS subtypes among children and adolescents based on stool diary information, and compared subtypes according to demographic and pain characteristics. METHODS We studied 129 subjects, ages 7 to 18 years (mean age, 11.4 ± 2.8 y; 60.5% female; 69.0% white) who met Pediatric Rome III IBS criteria and were part of larger studies of children with functional gastrointestinal disorders, recruited from primary and tertiary care centers. Children completed daily pain and stool diaries for 2 weeks. Participants were assigned IBS subtypes based on their reported stool information per adult Rome III criteria. IBS subtypes were compared for demographic variables and pain characteristics. RESULTS IBS with constipation was the most common subtype of the disorder (58.1% of subjects), whereas mixed IBS was the least common (2.3% of subjects); 34.1% of subjects were unsubtyped IBS and 5.4% had IBS with diarrhea. The groups of different IBS subtypes did not differ significantly by sex, age, ethnicity, or pain characteristics. CONCLUSIONS In contrast to adults, in children, IBS with constipation and unsubtyped IBS are the most common subtypes, whereas IBS with diarrhea and mixed IBS are less common. Demographic and pain characteristics cannot distinguish subtypes.

Psyllium Fiber Reduces Abdominal Pain in Children With Irritable Bowel Syndrome in a Randomized, Double-Blind Trial

Background & Aims We sought to determine the efficacy of psyllium fiber treatment on abdominal pain and stool patterns in children with irritable bowel syndrome (IBS). We evaluated effects on breath hydrogen and methane production, gut permeability, and microbiome composition. We also investigated whether psychological characteristics of children or parents affected the response to treatment. Methods We performed a randomized, double‐blind trial of 103 children (mean age, 13 ± 3 y) with IBS seen at primary or tertiary care settings. After 2 weeks on their habitual diet, children began an 8‐day diet excluding carbohydrates thought to cause symptoms of IBS. Children with ≥75% improvement in abdominal pain were excluded (n = 17). Children were assigned randomly to groups given psyllium (n = 37) or placebo (maltodextrin, n = 47) for 6 weeks. Two‐week pain and stool diaries were compared at baseline and during the final 2 weeks of treatment. We assessed breath hydrogen and methane production, intestinal permeability, and the composition of the microbiome before and after administration of psyllium or placebo. Psychological characteristics of children were measured at baseline. Results Children in the psyllium group had a greater reduction in the mean number of pain episodes than children in the placebo group (mean reduction of 8.2 ± 1.2 after receiving psyllium vs mean reduction of 4.1 ± 1.3 after receiving placebo; P = .03); the level of pain intensity did not differ between the groups. Psychological characteristics were not associated with response. At the end of the study period, the percentage of stools that were normal (Bristol scale scores, 3–5), breath hydrogen or methane production, intestinal permeability, and microbiome composition were similar between groups. Conclusions Psyllium fiber reduced the number of abdominal pain episodes in children with IBS, independent of psychological factors. Psyllium did not alter breath hydrogen or methane production, gut permeability, or microbiome composition. ClinicalTrials.gov no: NCT00526903.

Agreement between prospective diary data and retrospective questionnaire report of abdominal pain and stooling symptoms in children with irritable bowel syndrome

In functional gastrointestinal disorders, patient recall of symptoms drives diagnostic decisions and evaluation of treatment response, and research conclusions about potential treatments. In pediatrics, parent report also impacts assessment and care. Hence, identifying methods for accurately capturing patient and parent report of irritable bowel syndrome (IBS) symptoms is important. This study evaluated correspondence between retrospective questionnaire (parent and child report) and prospective diary data for children and adolescents with IBS.

Lactulose Breath Test Gas Production in Childhood IBS is Associated with Intestinal Transit and Bowel Movement Frequency.

Objectives: In adults with irritable bowel syndrome (IBS), bacterial gas production (colonic fermentation) is related to both symptom generation and intestinal transit. Whether gas production affects symptom generation, psychosocial distress, or intestinal transit in childhood IBS is unknown. Methods: Children (ages 7–17 years) with pediatric Rome III IBS completed validated psychosocial questionnaires and a 2-week daily diary capturing pain and stooling characteristics. Stool form determined IBS subtype. Subjects then completed a 3-hour lactulose breath test for measurement of total breath hydrogen and methane production. Carmine red was used to determine whole intestinal transit time. Results: A total of 87 children (mean age 13 ± 2.6 [standard deviation] years) were enrolled, of whom 50 (57.5%) were girls. All children produced hydrogen and 51 (58.6%) produced methane. Hydrogen and methane production did not correlate with either abdominal pain frequency/severity or psychosocial distress. Hydrogen and methane production did not differ significantly by IBS subtype. Methane production correlated positively with whole intestinal transit time (r = 0.31, P < 0.005) and inversely with bowel movement frequency (r = −0.245, P < 0.05). Methane production (threshold 3 ppm) as a marker for identifying IBS-C had a sensitivity of 60% and specificity of 42.9%. Conclusions: Lactulose breath test total methane production may serve as a biomarker of whole intestinal transit time and bowel movement frequency in children with IBS. In children with IBS, lactulose breath test hydrogen and methane production did not, however, correlate with abdominal pain, IBS subtype, or psychosocial distress.

Stooling Characteristics in Children With Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a highly prevalent and multifactorial functional gastrointestinal disorder affecting up to 20% of school-aged children worldwide. Clinically IBS is characterized by abdominal discomfort that improves with defecation and/or is associated with changes in stool frequency or stool form. Stool form in both adults and children often is assessed using the Bristol Stool Form Scale (BSFS). The BSFS categorizes stools into 1 of 7 stool types ranging from type 1 (hard lumps) to type 7 (watery diarrhea). Individuals with IBS are subtyped based on predominant stool form: IBS with constipation, IBS with diarrhea, IBS mixed subtype, and IBS unsubtyped. However, little is known about how children with IBS differ from healthy children (HC) with respect to either stool form or stool frequency.

Maintenance of Pain in Children With Functional Abdominal Pain.

Objectives: A significant proportion of children with functional abdominal pain develop chronic pain. Identifying clinical characteristics predicting pain persistence is important in targeting interventions. We examined whether child anxiety and/or pain-stooling relations were related to maintenance of abdominal pain frequency and compared the predictive value of 3 methods for assessing pain-stooling relations (ie, diary, parent report, child report). Methods: Seventy-six children (7–10 years old at baseline) who presented for medical treatment of functional abdominal pain were followed up 18 to 24 months later. Baseline anxiety and abdominal pain-stooling relations based on pain and stooling diaries and child- and parent questionnaires were examined in relationship to the persistence of abdominal pain frequency. Results: Childrens baseline anxiety was not related to persistence of pain frequency. Children who, however, displayed irritable bowel syndrome (IBS) symptoms at baseline maintained pain frequency at follow-up, whereas in children in whom there was no relationship between pain and stooling, pain frequency decreased. Pain and stool diaries and parent report of pain-stooling relations were predictive of pain persistence but child-report questionnaires were not. Conclusions: The presence of IBS symptoms in school-age children with functional abdominal pain appears to predict persistence of abdominal pain over time, whereas anxiety does not. Prospective pain and stooling diaries and parent report of IBS symptoms were predictors of pain maintenance, but child report of symptoms was not.