Bruno P. Chumpitazi

Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome.

A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet can ameliorate symptoms in adult irritable bowel syndrome (IBS) within 48 h.

Gut microbiota influences low fermentable substrate diet efficacy in children with irritable bowel syndrome

We sought to determine whether a low fermentable substrate diet (LFSD) decreases abdominal pain frequency in children with irritable bowel syndrome (IBS) and to identify potential microbial factors related to diet efficacy. Pain symptoms, stooling characteristics, breath hydrogen and methane, whole intestinal transit time, stool microbiome, and metabolite composition were collected and/or documented in eight children with IBS at baseline and during one week of an LFSD intervention. Pain frequency (P < 0.05), pain severity (P < 0.05), and pain-related interference with activities (P < 0.05) decreased in the subjects while on the LFSD. Responders vs. non-responders: four children (50%) were identified as responders (>50% decrease in abdominal pain frequency while on the LFSD). There were no differences between responders and non-responders with respect to hydrogen production, methane production, stooling characteristics, or gut transit time. Responders were characterized by increased pre-LFSD abundance of bacterial taxa belonging to the genera Sporobacter (P < 0.05) and Subdoligranulum (P < 0.02) and decreased abundance of taxa belonging to Bacteroides (P < 0.05) relative to non-responders. In parallel, stool metabolites differed between responders and non-responders and were associated with differences in microbiome composition. These pilot study results suggest that an LFSD may be effective in decreasing GI symptoms in children with IBS. Microbial factors such as gut microbiome composition and stool metabolites while on the diet may relate to LFSD efficacy.

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.

Absent Smooth Muscle Actin Immunoreactivity of the Small Bowel Muscularis Propria Circular Layer in Association with Chromosome 15q11 Deletion in Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS; OMIM%249210) is a rare and severe form of congenital intestinal and urinary dysfunction and malformation. Histologic studies suggest that the predominant intestinal manifestation is smooth muscle myopathy. Molecular observations have linked the disease to the neuronal nicotinic acetylcholine receptor (ηAChR), namely the absence of a functional α3 subunit of the ηAChR in patients with MMIHS. We describe a case of MMIHS in association with a de novo deletion of the proximal long arm of chromosome 15 (15q11.2). Histologic evaluation revealed an appropriate light microscopic appearance of both the circular and longitudinal layers of the small bowel muscularis propria. Immunohistochemical staining for smooth muscle actin, however, was selectively absent in the circular layer, demonstrating isolated absence in a unique and previously undescribed pattern. These observations raise the possibility that the proximal long arm of chromosome 15 (15q11) may be of clinical significance in MMIHS.

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.

Underlying molecular and cellular mechanisms in childhood irritable bowel syndrome.

Irritable bowel syndrome (IBS) affects a large number of children throughout the world. The symptom expression of IBS is heterogeneous, and several factors which may be interrelated within the IBS biopsychosocial model play a role. These factors include visceral hyperalgesia, intestinal permeability, gut microbiota, psychosocial distress, gut inflammation, bile acids, food intolerance, colonic bacterial fermentation, and genetics. The molecular and cellular mechanisms of these factors are being actively investigated. In this mini-review, we present updates of these mechanisms and, where possible, relate the findings to childhood IBS. Mechanistic elucidation may lead to the identification of biomarkers as well as personalized childhood IBS therapies.

Bristol Stool Form Scale reliability and agreement decreases when determining Rome III stool form designations.

Rater reproducibility of the Bristol Stool Form Scale (BSFS), which categorizes stools into one of seven types, is unknown. We sought to determine reliability and agreement by individual stool type and when responses are categorized by Rome III clinical designation as normal or abnormal (constipation or diarrhea).

Relationship of gastrointestinal symptoms and psychosocial distress to gastric retention in children.

OBJECTIVES To determine whether gastrointestinal (GI) symptoms (abdominal pain, nonpain GI symptoms, nausea) and/or psychosocial distress differ between children with/without gastroparesis and whether the severity of GI symptoms and/or psychosocial distress is related to the degree of gastroparesis. STUDY DESIGN Children aged 7-18 years (N = 100; 63 female patients) undergoing a 4-hour gastric emptying scintigraphy study completed questionnaires evaluating GI symptoms, anxiety, and somatization for this prospective study. Spearman correlation, Mann-Whitney, t-test, and χ(2) tests were used as appropriate for statistical analysis. RESULTS Children with gastroparesis (n = 25) were younger than those with normal emptying (12.6 ± 3.5 vs 14.3 ± 2.6 years, P = .01). Because questionnaire responses from 7- to 10-year-old children were inconsistent, only patient-reported symptoms from 11- to 18-year-olds were used. Within this older group (n = 83), children with gastroparesis (n = 17) did not differ from children with normal emptying in severity of GI symptoms or psychosocial distress. In children with gastroparesis, gastric retention at 4 hours was related inversely to vomiting (r = -0.506, P = .038), nausea (r = -0.536, P = .019), difficulty finishing a meal (r = -0.582, P = .014), and Childrens Somatization Inventory score (r = -0.544, P = .024) and positively correlated with frequency of waking from sleep with symptoms (r = 0.551, P = .022). CONCLUSIONS The severity of GI symptoms and psychosocial distress do not differ between children with/without gastroparesis who are undergoing gastric emptying scintigraphy. In those with gastroparesis, gastric retention appears to be inversely related to dyspeptic symptoms and somatization and positively related to waking from sleep with symptoms.

Fructans Exacerbate Symptoms in a Subset of Children With Irritable Bowel Syndrome

BACKGROUND & AIMS: Dietary fructans exacerbate symptoms in some, but not all, adults with irritable bowel syndrome (IBS). We sought to determine whether fructans worsen symptoms in children with IBS and whether clinical and psychosocial factors, and/or gas production, can identify those who are fructan sensitive. METHODS: We performed a double‐blind placebo‐controlled (maltodextrin) cross‐over trial of 23 children with IBS, based on pediatric Rome III criteria, from September 2014 through December 2016. At baseline, participants completed 1‐week pain and stool diaries and a 3‐day food record and psychosocial factors (depression, anxiety, and somatization) were measured. Subjects were randomly assigned to groups that were provided meals for 72 hours containing either fructans or maltodextrin (0.5 g/kg; maximum, 19 g). Following a washout period of 10 days or more, the subjects received the meal they were not given during the first study period (crossed over). Gastrointestinal symptoms and breath hydrogen and methane production were captured during each meal period. Fructan sensitivity was defined as an increase of 30% or more in abdominal pain frequency following fructan ingestion. RESULTS: Subjects had more mean episodes of abdominal pain/day during the fructan‐containing diet (3.4 ± 2.6) vs the maltodextrin‐containing diet (2.4 ± 1.7) (P < .01), along with more severe bloating (P < .05) and flatulence (P = .01). Hydrogen (but not methane) production was greater while subjects were on the fructan‐containing diet (617 ± 305 ppm*h) than the maltodextrin‐containing diet (136 ± 78 ppm*h) (P < .001). Eighteen subjects (78.2%) had more frequent abdominal pain while on the fructan‐containing diet and 12 (52.2%) qualified as fructan sensitive. We found no difference between fructan‐sensitive and fructan‐insensitive subjects in baseline abdominal pain or bowel movement characteristics, dietary intake, psychosocial parameters, IBS subtype, or gas production. CONCLUSIONS: In a randomized controlled trial of children with IBS, we found fructans to exacerbate several symptoms. However, fructan sensitivity cannot be identified based on baseline gastrointestinal symptoms, dietary intake, psychosocial factors, or gas production. Clinicaltrials.gov no: NCT02842281.

Gastric emptying scintigraphy results in children are affected by age, anthropometric factors, and study duration

A standardized 4‐h adult‐based gastric emptying scintigraphy (GES) protocol is increasingly being used in children to evaluate for gastroparesis. We sought to determine the effect of age, anthropometrics, and study duration on GES results using this protocol in children.