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OBJECTIVES: Fecal microbiota transplantation (FMT) is arguably the most effective treatment for recurrent Clostridioides difficile infection (rCDI). Clinical reports on pediatric FMT have not systematically evaluated microbiome restoration in patients with co-morbidities. Here we determined whether FMT recipient age and underlying co-morbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources. METHODS: Eighteen rCDI patients participating in a single-center, open-label prospective cohort study received fecal preparation from a self-designated (single case) or two universal donors. Twelve age-matched healthy children and 4 pediatric ulcerative colitis (UC) cases from an independent serial FMT trial, but with a shared fecal donor were examined as controls for microbiome restoration using 16S rRNA gene sequencing of longitudinal fecal specimens. RESULTS: FMT was significantly more effective in rCDI recipients without underlying chronic co-morbidities where fecal microbiome composition in post-transplant responders was restored to levels of healthy children. Microbiome reconstitution was not associated with symptomatic resolution in some rCDI patients who had co-morbidities. Significant elevation in Bacteroidaceae, Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae and Erysipelotrichaceae was consistently observed in pediatric rCDI responders, while Enterobacteriaceae decreased, correlating with augmented complex carbohydrate degradation capacity. CONCLUSION: Recipient background disease was a significant risk factor influencing FMT outcomes. Special attention should be taken when considering FMT for pediatric rCDI patients with underlying co-morbidities.

Background & Aims The role of the innate immune system in functional gastrointestinal pain disorders is unclear. We investigated the role of β-defensin-2 and gut permeability in childhood irritable bowel syndrome (IBS) and functional abdominal pain (FAP) symptom generation. Methods Fecal β-defensin-2 (and in a subset, gut permeability) was measured in children with IBS (n = 116), FAP (n = 33), and healthy control (HC) children (n = 72). IBS and FAP patients were recruited from tertiary and primary care, and HCs were recruited from primary care. Results β-defensin-2 concentration was greater in children with IBS (P = .003) and FAP (P = .03) than in HCs. β-defensin-2 was greater in girls with IBS than female HCs (P = .007) and in girls with IBS vs boys with IBS (P = .036). There was no difference by sex in the FAP and HC groups. For the entire cohort, β-defensin-2 correlated with multiple pain symptoms. In the IBS group, β-defensin-2 correlated with pain interference (P = .014). No correlation with pain was found in the FAP or HC group. Gut permeability was greater in the IBS vs the FAP and HC groups (P = .038). For the entire cohort, permeability correlated with the number of pain episodes (P = .041) and interfering pain episodes (P = .049). For the entire cohort there was a correlation between β-defensin-2 and permeability (P = .003), with borderline correlation in the IBS group (P = .086). For the cohort and IBS and HC groups, the number of bowel movements was modestly inversely related to fecal β-defensin-2 concentrations. Conclusions Increased fecal β-defensin-2 concentration in children with IBS suggests activation of the innate immune system in some, which, along with increased gut permeability, appears related to abdominal pain symptoms. Sex is an important variable in interpreting β-defensin-2 concentration in children with IBS.

OBJECTIVES: To test the hypothesis that in dyspeptic children, prospective symptom severity following ingestion of a meal would correlate with percent gastric retention, and those ultimately diagnosed with gastroparesis would report worse symptoms. STUDY DESIGN: Prospective, single center study with 104 children with dyspepsia completing a prospective dyspepsia symptom questionnaire before and after eating a standardized Tougas meal during gastric emptying scintigraphy (GES). Main outcomes included correlation between gastric retention and symptoms and comparison of symptom severity between those with and without gastroparesis. RESULTS: 52 children (50%) had gastroparesis (gastroparesis: 12.5 ± 2.9 years, 65% female; non-gastroparesis: 13.0 ± 2.9 years, 60% female; all P>0.05). Bloating was the only symptom significantly worse in youth with gastroparesis. For the entire cohort, bloating and fullness correlated with percent retention. However, in those with gastroparesis, only nausea correlated with retention (4 hr.; r(s)=0.275, P< .05). Girls with gastroparesis had significantly worse symptoms (except satiety) when compared with boys with gastroparesis (P

OBJECTIVES Four-hour gastric emptying scintigraphy (GES) is the recommended method to identify both adult and childhood gastroparesis (GP). Previous pediatric studies have, however, not used this standard. We sought to determine the characteristics and outcomes of children versus adolescents with GP using the 4-hour GES evaluation. METHODS We performed a retrospective chart review of pediatric patients diagnosed with GP by 4-hour GES (>10% retention at 4 hours). Demographics, body mass index, GP-related symptoms, comorbidities, etiologies, therapies (eg, medications), healthcare utilization, and response to therapy were captured systematically. Symptoms were compared from the initial versus last gastroenterology visit. Outcomes were categorized as no improvement; improvement (resolution of at least 1 symptom while remaining on therapy); and complete resolution of symptoms. RESULTS A total of 239 subjects (12.1 ± 4.1 years [mean ± standard deviation], 70% girls) were included. The identified characteristics of childhood GP were broad with idiopathic GP being the most common etiology. Outcomes over a median of 22 months (25%-75%: 9.0-45.5 months) were 34.8% no improvement, 34.8% some improvement, and 30.3% with complete symptom resolution. Compared to younger children, adolescents had a higher female predominance (P

Pigs are increasingly important animals for modeling human pediatric nutrition and gastroenterology and complementing mechanistic studies in rodents. The comparative advantages in size and physiology of the neonatal pig have led to new translational and clinically relevant models of important diseases of the gastrointestinal tract and liver in premature infants. Studies in pigs have established the essential roles of prematurity, microbial colonization, and enteral nutrition in the pathogenesis of necrotizing enterocolitis. Studies in neonatal pigs have demonstrated the intestinal trophic effects of akey gut hormone, glucagon-like peptide 2 (GLP-2), and its role in the intestinal adaptation process and efficacy in the treatment of short bowel syndrome. Further, pigs have been instrumental in elucidating the physiology of parenteral nutrition–associated liver disease and the means by which phytosterols, fibroblast growth factor 19, and a new generation of lipid emulsions may modify disease. The premature pig will continue to be a valuable model in the development of optimal infant diets (donor human milk, colostrum), specific milk bioactives (arginine, growth factors), gut microbiota modifiers (pre-, pro-, and antibiotics), pharmaceutical drugs (GLP-2 analogs, FXR agonists), and novel diagnostic tools (near-infrared spectroscopy) to prevent and treat these pediatric diseases.

Background:Little is known regarding the clinical impact of treatment and treatment duration of probiotic VSL#3 on gut and microbiome function in irritable bowel syndrome (IBS). As part of a safety trial, we assessed the effect of VSL#3 treatment duration on abdominal pain, stooling, gut permeability, microbiome composition and function.Methods:Adults with IBS were randomized into an open label trial to receive the probiotic VSL#3 for 4 or 8 weeks. Adverse events, abdominal pain, and stooling patterns were recorded daily. Gut permeability, fecal bile acid levels, and microbiome composition were profiled at baseline and after treatment.Results:Fifteen subjects completed the trial (4-week:n= 8; 8-week:n= 7). Number of pain episodes decreased in both groups (P= 0.049 andP= 0.034; 4- vs. 8-week, respectively). Probiotic organisms contained in VSL#3 were detected in feces by whole shotgun metagenomic sequencing analysis and relative abundances ofStreptococcus thermophilus, Bifidobacterium animalis, Lactobacillus plantarum, andLactobacillus caseisubsp.paraccaseicorrelated significantly with improved abdominal pain symptoms and colonic permeability at study completion. Although abdominal pain correlated significantly with the detection of probiotic species at study completion, a composite view of gut microbiome structure showed no changes in community diversity or composition after VSL#3 treatment.Conclusions:Probiotic organisms identified in stool correlated significantly with improvement in colonic permeability and clinical symptoms, prompting future studies to investigate the mechanistic role of VSL#3 and colonic permeability in IBS pathophysiology in a larger randomized controlled trial.Clinical Trial Registration:www.clinicaltrials.gov, Identifier: NCT00971711.

Background Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders. Aims 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA. Methods Patients were assessed with gastric emptying scintigraphy (GES), symptom assessment via Patient Assessment of Upper GI Symptoms [PAGI-SYM], and blood tests-ANA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). Results Positive ANA was seen in 148 of 893 (17%) patients with gastroparesis, being similar in idiopathic (16% of 536 patients), T1DM (16% of 162), T2DM (18% of 147), and postfundoplication (19% of 48 patients) gastroparesis. Among 536 patients with idiopathic gastroparesis, ANA titer 1:40-1:80 was seen in 33 (6%) patients, 1:160-1:320 in 36 (7%) patients, and ≥1:640 in 17 (3%) patients. Increasing ANA titer was associated with female gender (p = 0.05), Hispanic ethnicity (p = 0.02), comorbid rheumatoid arthritis (p = 0.02), systemic sclerosis (p = 0.004), and elevated ESR (p = 0.007). ANA positivity was associated with lower total GCSI (p = 0.007) and lower nausea/vomiting subscale (p = 0.0005), but not related to gastric emptying. Conclusions The prevalence of a positive ANA in patients with gastroparesis was high at ~17% and did not differ significantly based on etiology. In idiopathic patients, ANA positivity was associated with rheumatoid arthritis, systemic sclerosis, and elevated ESR. ANA-positive gastroparesis represents a subset who often have other autoimmune symptoms or disorders, but less severe nausea and vomiting.

Aims Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at three dose levels in children and determine their effects on gut motility and transit. Methods Thirty children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately one week later they were randomized to 180, 360, or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, 180 mg twice, or 180 mg thrice daily) for one week during which time the WMC test was repeated. Results Evaluable area under the plasma concentration vs. time curve (AUClast ) data were available in 29 of 30 participants. A direct linear relationship (apparent dose-proportionality for systemic menthol exposure) was observed between PMO dose and menthol systemic exposure with mean elimination half-life 2.1, 3.5, and 4.6 hours for the 180, 360, and 540 mg doses, respectively. WMC technical issues precluded complete motility data in all participants. Colonic transit time was inversely related to AUClast (P=0.003); transit time in other regions were not affected. In contrast, stomach, small bowel, and whole gut (but not colonic) contractility positively correlated with menthol AUClast (P Conclusions Pharmacokinetics and pharmacodynamics of menthol derived from PMO demonstrated apparent dose-proportionality. A higher dose of PMO may be needed to achieve maximal gut response. www.clinicaltrials.gov NCT03295747.

Background & Aims The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR). Methods The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. The control group did not use domperidone (non-DOM group) before or after enrollment. The following outcome measures were identified: change from baseline in Gastroparesis Cardinal Symptom Index total score, with 3 subscales, plus Gastroesophageal Reflux Disease and Patient Assessment of Upper Gastrointestinal Disorders–Quality of Life scores. Results Overall, of 748 patients, 181 (24%) were in the DOM group, whereas 567 were in the non-DOM group. Sixty-three percent of participants had idiopathic GP. At baseline, DOM patients compared with non-DOM patients were significantly younger, had lower body mass index, non-Hispanic ethnicity, a higher annual household income, lower narcotic utilization, lower supplemental and complimentary medication use, and were more likely to have delayed gastric emptying time, as well as worse nausea and fullness scores. Compared with non-DOM patients, DOM patients experienced moderate but significantly more improvement in GP outcome measures: Gastroparesis Cardinal Symptom Index total score (P = .003), nausea (P = .003), and fullness subscales (P =.005), upper abdominal pain score (P = .04), Gastroesophageal Reflux Disease score (P = .05), and Patient Assessment of Upper Gastrointestinal Disorders–Quality of Life score (P = .05). Conclusions Utilizing the method of pragmatic modeling to evaluate long-term treatment of GP in a large GpCRC database, DOM treatment resulted in moderately but significantly improved GP. Note This project was based on data generated by 2 GpCRC Registry studies recognized under the Clinicaltrial.gov numbers: NCT00398801 and NCT01696747 symptoms compared with a group receiving standard-of-care but not DOM.

Dietary management is key in controlling functional gastrointestinal disorders (FGIDs) symptoms. However, the degree to which patients with FGIDs in clinical studies adhere to dietary recommendations is unknown. Our aim was to evaluate adherence, dietary education, and adherence-related factors in FGIDs dietary intervention trials. A literature search was performed using MEDLINE, Google Scholar, and SCOPUS for clinical trials evaluating dietary management of FGIDs. Full manuscripts published from January 2000 through August 2018 were reviewed. Data including definitions of adherence and rates, study design, dietary education, use of a dietitian, provision of study foods, potential adherence barriers, and dropouts were captured. A total of 21 publications were included. Fifteen (67%) focused on the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, 5 (24%) on fiber supplementation, and 1 (9%) on a low carbohydrate diet. Fifteen (71%) were randomized controlled trials. Meals/supplements were provided to the study participants in 27%, 80%, and 100%, of the low FODMAP, fiber, and low carbohydrate studies, respectively, which appeared to significantly enhance adherence (P

Accurate diagnosis and stratification of children with irritable bowel syndrome (IBS) remain challenging. Given the central role of recurrent abdominal pain in IBS, we evaluated the relationships of pediatric IBS and abdominal pain with intestinal microbes and fecal metabolites using a comprehensive clinical characterization and multiomics strategy. Using rigorous clinical phenotyping, we identified preadolescent children (aged 7 to 12 years) with Rome III IBS (n = 23) and healthy controls (n = 22) and characterized their fecal microbial communities using whole-genome shotgun metagenomics and global unbiased fecal metabolomic profiling. Correlation-based approaches and machine learning algorithms identified associations between microbes, metabolites, and abdominal pain. IBS cases differed from controls with respect to key bacterial taxa (eg, Flavonifractor plautii and Lachnospiraceae bacterium 7_1_58FAA), metagenomic functions (eg, carbohydrate metabolism and amino acid metabolism), and higher-order metabolites (eg, secondary bile acids, sterols, and steroid-like compounds). Significant associations between abdominal pain frequency and severity and intestinal microbial features were identified. A random forest classifier built on metagenomic and metabolic markers successfully distinguished IBS cases from controls (area under the curve, 0.93). Leveraging multiple lines of evidence, intestinal microbes, genes/pathways, and metabolites were associated with IBS, and these features were capable of distinguishing children with IBS from healthy children. These multi-omics features, and their links to childhood IBS coupled with nutritional interventions, may lead to new microbiome-guided diagnostic and therapeutic strategies.

OBJECTIVE Imaging studies in adults with irritable bowel syndrome (IBS) have shown both morphological and resting state (RS) functional connectivity (FC) alterations related to cortical modulation of sensory processing. Because analogous differences have not been adequately investigated in children, this study compared gray matter volume (GMV) and RS-FC between girls with IBS and healthy controls (HC) and tested the correlation between brain metrics and laboratory-based pain thresholds (Pth). METHODS Girls with Rome III criteria IBS (n = 32) and matched HCs (n = 26) were recruited. In a subset of patients, Pth were determined using a thermode to the forearm. Structural and RS scans were acquired. A voxel-based general linear model, adjusting for age, was applied to compare differences between groups. Seeds were selected from regions with group GMV differences for a seed-to-voxel whole brain RS-FC analysis. Significance for analyses was considered at p < .05 after controlling for false discovery rate. Significant group differences were correlated with Pth. RESULTS Girls with IBS had lower GMV in the thalamus, caudate nucleus, nucleus accumbens, anterior midcingulate (aMCC), and dorsolateral prefrontal cortex. They also exhibited lower RS-FC between the aMCC and the precuneus, but greater connectivity between the caudate nucleus and precentral gyrus. Girls with IBS had higher Pth with a moderate effect size (t(22.81) = 1.63, p = .12, d = 0.64) and lower thalamic GMV bilaterally was correlated with higher Pth (left: r = -.62, p(FDR) = .008; right: r = -.51, p(FDR) = .08). CONCLUSIONS Girls with IBS had lower GMV in the PFC, basal ganglia, and aMCC, as well as altered FC between multiple brain networks, suggesting that structural changes related to IBS occur early in brain development. Girls with IBS also showed altered relationships between pain sensitivity and brain structure.

BACKGROUND Understanding factors that impair quality of life (QOL) in gastroparesis is important for clinical management. AIMS (a) Determine QOL in patients with gastroparesis; (b) Determine factors that impair QOL. METHODS Gastroparetic patientsAQ6 underwent history and questionnaires assessing symptoms (PAGI-SYM and Rome III), QOL (SF-36v2 and PAGI-QOL), depression (Beck Depression Inventory [BDI]), and anxiety (State Trait Anxiety InventoryAQ7). KEY RESULTS 715 gastroparesis patients (256 diabetic (DG), 459 idiopathic (IG)) were evaluated. SF-36 physical component (PC) score averaged 33.3 ± 10.5; 41% had impaired score

Background & Aims Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI transit delays assessed by gastric emptying scintigraphy (GES) and wireless motility capsule (WMC). Methods Patients with symptoms of gastroparesis underwent gastric emptying scintigraphy (GES), wireless motility capsule (WMC) assessing gastric emptying, small bowel transit, and colonic transit, and questionnaires assessing symptoms using a modified Patient Assessment of Upper GI Symptoms [PAGI-SYM] and Rome III functional GI disorder questionnaire. Results Of 338 patients with symptoms of gastroparesis, 242 (71.5%) had delayed gastric emptying by scintigraphy; 298 (88.2%) also met criteria for functional dyspepsia. Severity of constipation was severe/very severe in 34% patients, moderate in 24%, and none/very mild/mild in 42%. Increasing severity of constipation was associated with increasing symptoms of gastroparesis and presence of irritable bowel syndrome (IBS). Severity of constipation was not associated with gastric retention on GES or WMC. Delayed colonic transit was present in 108 patients (32% of patients). Increasing severity of constipation was associated with increasing small bowel transit time, colonic transit time, and whole gut transit time. Conclusions Severe/very severe constipation and delayed colon transit occurs in a third of patients with symptoms of gastroparesis. The severity of constipation is associated with severity of gastroparesis symptoms, presence of IBS, small bowel and colon transit delay, but not delay in gastric emptying. ClinicalTrials.gov Identifier: NCT01696747

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. High bile acid (BA) profiles have been associated with abdominal pain symptoms, mucosal inflammation, and diarrhea in a subgroup of those with IBS. The purpose of this study was to compare: 1) fecal primary and secondary BAs in women with and without IBS; and 2) symptoms, gut microbiome, and diet between women with high and normal BAs (i.e., similar to healthy [HC] women). Women (ages 18–45) with IBS and HCs were recruited from healthcare providers or the community. Participants kept a 28-day symptom diary, completed a 3-day food journal, and collected a stool sample for microbiome analysis (16 S rRNA gene sequencing). Primary and secondary BA levels were determined by mass spectrometry. Primary BAs did not differ between IBS (n = 45) and HC (n = 28) groups; women with IBS had significantly increased conjugated secondary BAs (glycodeoxycholic acid [ p = 0.006], taurodeoxycholic acid [ p = 0.006], and glycolithocholic acid [ p = 0.01]). Sixty percent of women with IBS had normal BAs whereas 40% had high BAs. Women with high fecal BAs were predominantly IBS-Diarrhea or IBS-Mixed and consumed less fiber and vegetable protein and more animal protein compared to women with IBS whose fecal BAs levels were comparable to HCs. Those with high conjugated secondary fecal BAs also had a greater Firmicutes/Bacteroidetes ratio, less abundance of phylum Bacteroidetes and genus Gemmiger, and more abundance of family Erysipelotrichaceae compared to IBS women with normal BAs. Determination of fecal BA levels provides additional insights into pathophysiological links between diet and microbiome in IBS.

Background The aim of this study was to clarify the pathophysiology of functional dyspepsia (FD), a highly prevalent gastrointestinal syndrome, and its relationship with the better-understood syndrome of gastroparesis. Methods Adult patients with chronic upper gastrointestinal symptoms were followed up prospectively for 48 weeks in multi-center registry studies. Patients were classified as having gastroparesis if gastric emptying was delayed; if not, they were labeled as having FD if they met Rome III criteria. Study analysis was conducted using analysis of covariance and regression models. Results Of 944 patients enrolled during a 12-year period, 720 (76%) were in the gastroparesis group and 224 (24%) in the FD group. Baseline clinical characteristics and severity of upper gastrointestinal symptoms were highly similar. The 48-week clinical outcome was also similar but at this time 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis. Change in either direction was not associated with any difference in symptom severity changes. Full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with obese controls. Conclusions A year after initial classification, patients with FD and gastroparesis, as seen in tertiary referral centers at least, are not distinguishable based on clinical and pathologic features or based on assessment of gastric emptying. Gastric-emptying results are labile and do not reliably capture the pathophysiology of clinical symptoms in either condition. FD and gastroparesis are unified by characteristic pathologic features and should be considered as part of the same spectrum of truly "organic" gastric neuromuscular disorders. ClinicalTrials.gov Identifier NCT00398801, NCT01696747

INTRODUCTION: Altered microbial diversity has been associated with gastrointestinal (GI) symptoms in persons with irritable bowel syndrome (IBS). Less is known about the relationship of microbiome with extra-intestinal pain and psychological distress symptoms and quality of life (QOL) in persons with IBS. We aimed to evaluate the relationship of fecal microbiota to GI symptoms, stool consistency, psychological distress, extra-intestinal pain, and QOL in participants meeting Rome III criteria for IBS. METHODS: Seventy-six women completed a 28-day diary that included GI, stool consistency, psychological distress, and extra-intestinal pain ratings. Participants completed the IBS-Specific-Quality of Life questionnaire. Stool samples were collected and analyzed by 16S rRNA gene sequencing. Principal component analysis was performed and the first two components (PC1, PC2) were used to test relationships among bacterial families and clinical measures. RESULTS: Participants were categorized as IBS-constipation (n=22), IBS-diarrhea (n=39), IBS-mixed (n=13), and IBS-unsubtyped (n=2). There was a significant group effect for the Firmicutes to Bacteroidetes (FB) ratio and PC1. Lower microbial diversity and richness were associated with increased urgency and extra-intestinal pain, worse QOL, and looser stools. Lower extra-intestinal pain was associated with increased Rikenellaceae, Christensenellaceae, Dehalobabacteriaceae, Oscillospiraceae, Mogibacteriaceae, Ruminococcaceae, Sutterellaceae, Desulfovibrionaceae, and Erysipelotrichaceae abundances. QOL was positively associated with many of these same bacterial families. Higher FB ratio was positively associated with loose stools. There were no statistically significant relationships between daily psychological distress or abdominal pain and bacterial families. CONCLUSION: Stool microbial diversity and composition are linked to daily extra-intestinal symptoms, stool consistency, and QOL in women with IBS.

To test the hypothesis that the prevalence of joint hypermobility is greater in children with irritable bowel syndrome and functional abdominal pain than in healthy control children and is related to gastrointestinal symptoms and psychosocial distress (anxiety, depression, and somatization).Children (irritable bowel syndrome, n = 109; functional abdominal pain, n = 31; healthy control, n = 69), 7-12 years of age completed prospective 2-week pain and stooling diaries and child- and parent-reported measures of anxiety, depression, and somatization. Joint hypermobility was determined using Beighton criteria (score of ≥4 or 6). We also examined possible relationships between Beighton score, race, body mass index, gastrointestinal symptoms, and psychosocial distress.Beighton scores were similar between groups, as was the proportion with joint hypermobility. Scores were higher in girls (3.1 ± 2.4) than boys (2.3 ± 1.8; P = .004) and decreased with age (P .001; r = -0.25). Race and body mass index did not impact joint hypermobility prevalence. Beighton scores were not related to abdominal pain or stooling characteristics. Participants with a score of ≥4 and ≥6 had greater somatization and depression by child report (P = .017 and P = .048, respectively). No association was seen for anxiety. There was no significant association between joint hypermobility and psychosocial distress measures per parent report.Contrary to the adult literature, the prevalence of joint hypermobility does not differ among children with irritable bowel syndrome, functional abdominal pain, or healthy control children. The presence or severity of joint hypermobility does not correlate with abdominal pain or stooling characteristics. Somatization and depression by child report appear to have a relationship with joint hypermobility.

Previously we showed that urine trefoil factor 3 (TFF3) levels were higher in females with irritable bowel syndrome (IBS) compared to non-IBS females. To assess if TFF3 is associated with symptoms and/or reflect alterations in gastrointestinal permeability and gut microbiota in an IBS population, we correlated stool and urine TFF3 levels with IBS symptoms, intestinal permeability, stool microbial diversity and relative abundance of predominant bacterial families and genera. We also tested the relationship of stool TFF3 to urine TFF3, and compared results based on hormone contraception use. Samples were obtained from 93 females meeting Rome III IBS criteria and completing 4-week symptom diaries. TFF3 levels were measured by ELISA. Permeability was assessed with the urine lactulose/mannitol (L/M) ratio. Stool microbiota was assessed using 16S rRNA. Stool TFF3, but not urine TFF3, was associated positively with diarrhoea and loose stool consistency. Higher stool TFF3 was also associated with lower L/M ratio and microbial diversity. Of the 20 most abundant bacterial families Mogibacteriaceae and Christensenellaceae were inversely related to stool TFF3, with only Christensenellaceae remaining significant after multiple comparison adjustment. There were no significant relationships between stool or urine TFF3 levels and other symptoms, nor between stool and urine levels. In premenopausal females, urine TFF3 levels were higher in those reporting hormone contraception. Collectively these results suggest that higher stool TFF3 levels are associated with IBS symptoms (loose/diarrhoeal stools), lower gut permeability, and altered stool bacteria composition (decreased diversity and decreased Christensenellaceae), which further suggests that TFF3 may be an important marker of host-bacteria interaction.

BACKGROUND Gastric electrical stimulation (GES) for treating gastroparesis symptoms is controversial. METHODS We studied 319 idiopathic or diabetic gastroparesis symptom patients from the Gastroparesis Clinical Research Consortium (GpCRC) observational studies: 238 without GES and 81 with GES. We assessed the effects of GES using change in GCSI total score and nausea/vomiting subscales between baseline and 48 weeks. We used propensity score methods to control for imbalances in patient characteristics between comparison groups. KEY RESULTS GES patients were clinically worse (40% severe vs. 18% for non-GES; P

BACKGROUND Diet therapies may be recommended for pediatric functional gastrointestinal disorders (FGIDs). However, little is known about the frequency with which diet therapy is recommended in FGIDs. Our aims were to determine and contrast the frequency and types of diet recommendations provided to children with FGIDs by pediatric gastroenterologists (PGIs) versus primary care pediatricians (PCPs). METHODS A retrospective chart review was performed using data from a large, metropolitan children's academic healthcare system to identify subjects meeting Rome IV criteria for functional abdominal pain, functional dyspepsia, irritable-bowel syndrome (IBS), and/or abdominal migraine over a period of 23 months. RESULTS Of 1929 patient charts reviewed, 268 were included for further analyses. Of these, 186 patients (69%) were seen by a PGI and 82 (31%) by a PCP. The most common diagnosis was IBS (49% for PGIs and 71% for PCPs). Diet recommendations were provided to 115 (43%) patients (PGI group: 86 [75%] vs PCP group: 29 [25%]; P < .1). The most frequent recommendations were high fiber (PGI: 15%; PCP: 14%) and low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) diet (PGI: 12%; PCP: 4%). Of those provided with diet recommendations, only 20% (n = 23) received an educational consult by a dietitian. Provision of diet recommendations was not affected by years in practice. CONCLUSION Despite increasing awareness of the role of diet in the treatment of childhood FGIDs, a minority of patients receive diet recommendations in tertiary care or primary care settings. When diet recommendations were given, there was great variability in the guidance provided.

The low-FODMAP diet has emerged as an option for the treatment of irritable bowel syndrome (IBS). This diet is very restrictive, and compliance is usually low. Preliminary findings suggest an association between eating disorders (EDs) and the risk of developing IBS. The aim of this study was to assess the correlation between compliance with a low-FODMAP diet and the risk of ED behaviours among patients with IBS.A single-centre prospective study was carried out among 233 IBS patients (79.8% females) at University College London Hospital, who commenced a low FODMAPs group programme for IBS (Rome III or IV). Self-reported diet adherence at the end of the 6-week programme was measured. At baseline, and at the 6-week follow-up visit, participants completed the validated IBS-Symptom Severity Score, the SCOFF ED screening questionnaire and the Hospital Anxiety and Depression Scale.Adherence with a low-FODMAP diet was found in 95 (41%) patients. Overall, 54 (23%) patients were classified to be at risk for ED behaviour. Adherence was 57% in the ED group (31/54) versus 35% in the non-ED group (64/179); P0.05. Adherence with a low-FODMAP diet was highest (51%) in the IBS with diarrhoea subtype and lowest (10%) in IBS with constipation. There was no significant correlation between IBS-Symptom Severity Score and either adherence (P=0.39) or ED behaviour (P=0.28).In this IBS cohort, greater adherence to a low-FODMAP diet is associated with ED behaviour. The implications of our study are important in clinical practice for a clinician to have a high index of suspicion of EDs in IBS patients when a high level of low-FODMAP diet achieved.

INTRODUCTION Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life. METHODS A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12-23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L). RESULTS Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02). DISCUSSION Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.

BACKGROUND: Anxiety and depression are implicated as contributors to abdominal pain in pediatric irritable bowel syndrome (IBS) but is unclear if this pain is associated with other psychological factors. The study objective was to test if the impact of anxiety or depression on IBS symptom severity is mediated by somatization and/or pain catastrophizing. METHODS: We utilized baseline data from local pediatric IBS clinical studies. Through mediation analysis, we assessed whether somatization or pain catastrophizing mediated (either independently or combined) the separate relationships of anxiety or depression with IBS abdominal pain severity. KEY RESULTS: We analyzed 261 participants. All psychological factors were positively correlated with one another and IBS abdominal pain severity. The association of anxiety with IBS abdominal pain was mediated by both somatization and pain catastrophizing in individual analyses (each mediated standardized coefficient [β] 0.11, CI 0.05 – 0.18) and in multiple analysis (mediated standardized β 0.18, CI 0.09 – 0.27). The association of depression with IBS abdominal pain was also mediated by somatization (mediated standardized β 0.08, CI 0.02 – 0.14) and pain catastrophizing (mediated standardized β 0.06, CI 0.01 – 0.11) in individual analyses and in multiple analysis (mediated standardized β 0.19, CI 0.04 – 0.19). CONCLUSIONS & INFERENCES: Somatization and pain catastrophizing mediate the relationships between anxiety/depression and IBS abdominal pain severity. These findings suggest that somatization and pain catastrophizing may be better treatment targets than anxiety and depression. Clinicians should assess these psychological factors in pediatric IBS patients and refer for intervention to improve outcomes.

To investigate the patient-reported multidimensional gastrointestinal symptoms predictors of generic health-related quality of life (HRQOL) in pediatric patients with functional gastrointestinal disorders (FGIDs). The Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales and PedsQL™ 4.0 Generic Core Scales were completed in a 9-site study by 259 pediatric patients with functional constipation, functional abdominal pain (FAP), or irritable bowel syndrome (IBS). Gastrointestinal Symptoms Scales measuring stomach pain, stomach discomfort when eating, food and drink limits, trouble swallowing, heartburn and reflux, nausea and vomiting, gas and bloating, constipation, blood in poop, and diarrhea were identified as clinically important symptom differentiators from healthy controls based on prior findings, and subsequently tested for bivariate and multivariate linear associations with overall HRQOL. Gastrointestinal symptoms were differentially associated with decreased HRQOL in bivariate analyses for the three FGIDs. In predictive models utilizing hierarchical multiple regression analyses controlling for age, gender, and race/ethnicity, gastrointestinal symptoms differentially accounted for an additional 47, 40, and 60 % of the variance in patient-reported HRQOL for functional constipation, FAP, and IBS, respectively, reflecting large effect sizes. Significant individual gastrointestinal symptoms predictors were identified after controlling for the other gastrointestinal symptoms in the FGID-specific predictive models. Gastrointestinal symptoms represent potentially modifiable predictors of generic HRQOL in pediatric patients with FGIDs. Identifying the condition-specific gastrointestinal symptoms that are the most important predictors from the patient perspective facilitates a patient-centered approach to targeted interventions designed to ameliorate impaired overall HRQOL.

BACKGROUND/AIMS To determine if potential biomarkers can be used to identify subgroups of people with irritable bowel syndrome (IBS) who will benefit the most or the least from a comprehensive self-management (CSM) intervention. METHODS In a two-armed randomized controlled trial a CSM (n = 46) was compared to a usual care (n = 46) group with follow-up at 3 and 6 months post randomization. Biomarkers obtained at baseline included heart rate variability, salivary cortisol, interleukin-10 produced by unstimulated peripheral blood mononuclear cells, and lactulose/mannitol ratio. Linear mixed models were used to test whether these biomarkers predicted improvements in the primary outcomes including daily abdominal pain, Gastrointestinal Symptom score and IBS-specific quality of life. RESULTS The nurse-delivered 8-session CSM intervention is more effective than usual care in reducing abdominal pain, reducing Gastrointestinal Symptom score, and enhancing quality of life. Participants with lower nighttime high frequency heart rate variability (vagal modulation) and increased low frequency/high frequency ratio (sympathovagal balance) had less benefit from CSM on abdominal pain. Salivary cortisol, IL-10, and lactulose/mannitol ratio were not statistically significant in predicting CSM benefit. Baseline symptom severity interacts with treatment, namely the benefit of CSM is greater in those with higher baseline symptoms. CONCLUSIONS Cognitively-focused therapies may be less effective in reducing abdominal pain in IBS patients with higher sympathetic tone. Whether this a centrally-mediated patient characteristic or related to heightened arousal remains to be determined.

Background & Aims Increased gut permeability might contribute to the pathogenesis of irritable bowel syndrome or functional abdominal pain (IBS or FAP). We investigated whether siblings and parents of children with IBS or FAP have increased gut permeability. Methods We performed permeability tests (using sucrose, lactulose, mannitol, and sucralose) on 29 siblings and 43 parents of children with IBS or FAP, and 43 children (controls) and 42 parents of controls, from primary and secondary care. Permeability studies were repeated in 7 siblings and 37 parents of children with IBS or FAP and 23 controls and 36 parents of controls following ingestion of 400 mg of ibuprofen. Percent recovery of sucrose was calculated based on analyses of urine collected overnight; the lactulose/mannitol ratio and percent recovery of sucralose were based on analyses of urine samples collected over a 24-hour period. Results When we controlled for age, sex, and family membership, siblings of children with IBS or FAP had increased small bowel permeability (urinary lactulose/mannitol ratio) vs controls (P = .004). There was no difference in gastroduodenal (percent sucrose recovery) or colonic (percent sucralose recovery) permeability between groups. Similarly, parents of children with IBS or FAP also had increased small bowel permeability, compared with parents of controls (P = .015), with no differences in gastric or colonic permeability. After administration of ibuprofen, gastroduodenal and small bowel permeability tended to be greater in IBS or FAP siblings (P = .08) and gastroduodenal permeability tended to be greater in IBS or FAP parents (P = .086). Conclusions Siblings and parents of children with IBS or FAP have increased baseline small intestinal permeability compared with control children and their parents. These results indicate that there are familial influences on gastrointestinal permeability in patients with IBS or FAP.

Background Granins have been implicated in the pathophysiology of irritable bowel syndrome (IBS) in adults. We sought to determine whether fecal granins are altered in children with IBS and associated with symptoms. Methods Children (7-12 years of age) with IBS and healthy controls (HC) kept daily pain and stool diaries for 2 weeks. Stool samples were analyzed for chromogranins A and B (CgA, CgB) and secretogranins II and III (SgII, SgIII). Children also completed psychological measures to assess anxiety, depression, somatization, and internalizing symptoms. Key results Fecal CgB and SgIII concentrations were higher in all the boys (IBS plus HC, n = 48) than in all the girls (IBS plus HC, n = 75) (P = 0.02 and P = 0.046, respectively). CgA and SgIII were greater in children with IBS (n = 52) vs HC (n = 69) (P = 0.01, P = 0.017, respectively). CgB and SgII did not differ between groups. In children with IBS, the number of pain episodes per week and mean daily pain rating correlated positively with all four granins. The number of stools per day correlated positively with CgB and SgII, and the percent of diarrheal stools (6 or 7 on the Bristol Scale) correlated inversely with all four granins in boys but not in girls. Fecal granins did not correlate with psychological measures. Conclusions and inferences As measured by fecal granins, there is evidence of neuroimmune activation in children with IBS. Granins are related to abdominal pain symptoms, stooling frequency, and stool form in children with IBS. Sex influences the fecal concentration of CgB and SgIII.

This study examined gut permeability in unmedicated adolescents with and without major depressive disorder.Medically healthy, non-medicated, 12-17 year-old females in a major depressive episode (MDE) or healthy controls, without any psychiatric condition, were enrolled. They completed the Children's Depression Rating Scale-Revised (CDRS-R) and underwent a clinical interview. Preejection period (PEP) and respiratory sinus arrhythmia (RSA) data were collected to measure autonomic nervous system activity. Following an overnight fast, participants ingested lactulose and mannitol and collected urine for 4 hours while still fasting, to examine gut permeability. Plasma cytokines (interleukin 1β, interleukin 6, and tumor necrosis factor α) were measured. Correlational analyses were used to examine the associations between relevant variables.41 female participants (age: 14.8 ± 1.6 years, n = 25 with MDE) were enrolled. PEP, but not RSA, was inversely associated with neurovegetative symptom severity on the CDRS-R (r = -0.31, p 0.06). In the 30 participants with gut permeability data, the lactulose to mannitol ratio (LMR) was significantly positively associated with depression severity, particularly neurovegetative symptom severity (r = 0.37, p 0.05). Notably, the association between neurovegetative symptom severity and PEP was substantially reduced after adjusting for LMR. Additionally, depression severity was significantly associated with circulating cytokines.This is the first study to examine gut permeability in unmedicated adolescents, offering preliminary support for a mechanistic pathway linking sympathetic nervous system activation to increased gut permeability and activation of the innate immune system, likely contributing to the emergence of neurovegetative symptoms of depression.

Esophageal food impaction (EFI) can be the initial presentation of eosinophilic esophagitis (EoE). EoE is characterized by persistent esophageal eosinophilia (EE). Both EFI and EE are related to a variety of conditions. To date, the relationship between EFI, EE, and EoE remains unclear. To review our institutional experience with EFIs and combine our knowledge with the existing literature to conduct a systematic review and meta-analysis for delineating the relationship between EFI, EE, and EoE. We reviewed medical records of 72 children with EFI presenting to our emergency center between 2007 and 2013. PubMed, EMBASE, and Scopus databases were screened from inception until July 2014 to identify studies linking EFI and EoE. Included studies were methodically assessed for the quality and strength of association between EFI and EoE. Our institutional experience highlighted the possibility of proton-pump inhibitor therapy-responsive EE (PPI-REE) as an underrecognized risk factor for EFI. A systematic review of 14 studies, including ours, revealed that most studies did not eliminate other causes of EFI or EE. The meta-analysis revealed that esophageal biopsies were obtained from 54 % (40–68) of individuals presenting with EFI, and the overall EoE-attributable EFI among those who were biopsied was 54 % (43–65). Substantial heterogeneity was noted among the studies. PPI-REE is an underestimated risk factor for EFI. The quality of existing evidence linking EFI and EoE is limited by several important factors. Future studies with robust design are warranted to delineate the relationship between EFI, EE, and EoE.

Changes in the intestinal microbiome of patients with short bowel syndrome (SBS) are thought to significantly affect clinical outcome. These changes may not only delay enteral diet advancement but may also predispose patients to bacterial translocation, bacteremia, and liver disease. Patients with SBS are thought to be more susceptible to changes in gut microbial communities due to intestinal dysmotility and/or lack of anatomic safeguards such as the ileocecal valve.We analyzed the bacterial composition of 21 fecal specimens from 9 children with SBS and 8 healthy children ages 4 months to 8 years by 16S ribosomal RNA gene sequencing. The sequences were quality filtered and analyzed using QIIME, the Ribosomal Database Project Classifier, and the randomForest supervised learning algorithm.The fecal microbiome of patients with SBS is different from that of healthy controls. Stool from patients with SBS had a significantly greater abundance of the bacterial classes Gammaproteobacteria and Bacilli. Stool from patients with SBS who experienced increased stool frequency tended to have increased abundance of Lactobacillus (P = .057) and decreased abundance of Ruminococcus.This study shows that the fecal microbiome of patients with SBS is significantly different from that of healthy controls when analyzed by 16S metagenomics. Differences in the composition and function of gut microbiomes in children with SBS may affect bowel physiology, and these findings may provide new opportunities for intestinal rehabilitation and clinical management.

BACKGROUND Patient-reported outcomes are essential in determining the broad impact of inflammatory bowel disease (IBD) and treatments from the patient's perspective. The primary study objectives were to compare the gastrointestinal symptoms and worry of pediatric patients with IBD with matched healthy controls and to compare Crohn's disease and ulcerative colitis with each other using the Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms and Gastrointestinal Worry Scales. METHODS PedsQL Gastrointestinal Symptoms and Worry Scales were completed in a 9-site study by 256 pediatric patients with IBD and 259 parents of patients (263 families; Crohn's disease [n = 195], ulcerative colitis [n = 68]). Ten Gastrointestinal Symptoms Scales measuring stomach pain, stomach discomfort when eating, food and drink limits, trouble swallowing, heartburn and reflux, nausea and vomiting, gas and bloating, constipation, blood in poop, and diarrhea were administered along with 2 Gastrointestinal Worry Scales. A matched group of 384 healthy children families completed the PedsQL in an Internet survey. RESULTS PedsQL Gastrointestinal Symptoms and Worry Scales distinguished between pediatric patients with IBD in comparison with healthy controls (P < 0.001), with larger effect sizes for symptoms indicative of IBD, supporting known-groups validity and clinical interpretability including minimal important difference scores. Patients with Crohn's disease or ulcerative colitis did not demonstrate significantly different gastrointestinal symptoms or worry in comparison with each other. CONCLUSIONS The PedsQL Gastrointestinal Symptoms and Worry Scales may be used as common metrics across pediatric patients with IBD, including Crohn's disease and ulcerative colitis separately to measure gastrointestinal-specific symptoms in clinical research and practice.

Background 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. Methods Retrospective review of children who underwent a 4-h solid-meal GES study at a tertiary care center. GES results and anthropometric data (e.g., weight, stature, body surface area [BSA]) were systematically captured. Key Results Of 216 children, 188 (87%) were able to complete the study meal. Children unable to complete the meal were younger and smaller. In multivariate analysis, only increasing BSA was identified as being positively associated with ability to complete the meal (odds ratio: 19.7; p 10%). These children were significantly younger and smaller than those with normal emptying. In multivariate analysis of those completing the meal, only increasing BSA (odds ratio: 0.26; p = 0.006) was identified as being negatively associated with delayed emptying. There was a progressive increase in the positive predictive value for identification of delayed gastric emptying as the duration of the study increased (0.25, 0.60, and 0.71 at 1, 2, and 3 h, respectively) using the 4-hr value as a comparator. Conclusions & Inferences Young children have more difficulty completing the GES meal. Childhood gastric retention is affected by age and anthropometric factors, primarily BSA. The standardized 4-h GES protocol may need to take these factors into account in children.

Background Environmental enteropathy (EE) is subclinical, diffuse villous atrophy characterized by T cell infiltration of the small intestinal mucosa associated with nutrient malabsorption and stunting. EE is assessed by the lactulose:mannitol (L:M) test, whereby nonmetabolized sugars are ingested and quantified in the urine. Multiple micronutrient (MN) deficiency morphologically mimics EE, and ω-3 (n-3) polyunsaturated fatty acids reduce mucosal inflammation in Crohn disease. Objective We tested the hypothesis that supplementary MNs, with or without fish oil (FO), would improve L:M in rural Malawian children aged 1-3 y compared with a control (C) group receiving a placebo. Methods The MNs and FO provided the Recommended Dietary Intake for 26 vitamins, minerals, eicosapentaenoic acid, and docosahexaenoic acid. This was a 3-arm, randomized, double-blind, placebo-controlled clinical trial, with the primary outcomes being the change in L:M (ΔL:M) after 12 and 24 wk of supplementation. Comparisons were made for ΔL:M after 12 and 24 wk within each group by using a Wilcoxon matched pairs signed rank test, because the data are not normally distributed. Results A total of 230 children had specimens adequate for analysis; all had an abnormal baseline L:M, defined as >0.10. After 12 wk, children who received MNs + FO had a ΔL:M [mean (95% CI)] of -0.10 (-0.04, -0.15; P = 0.001), and children receiving only MNs had ΔL:M of -0.12 (-0.03, -0.21; P = 0.002). After 24 wk, children who received MNs + FO had a ΔL:M of -0.09 (-0.03, -0.15; P = 0.001); children receiving only MNs had a ΔL:M of -0.11 (-0.02, -0.20; P = 0.001), and the C group had ΔL:M of -0.07 (0.02, -0.16); P = 0.002). Linear growth was similar in all groups, ∼4.3 cm over 24 wk. Conclusion Although the effect was modest, these data suggest MNs can transiently ameliorate EE in rural African children. The trial was registered at clinicaltrials.gov as NCT01593033.

A 34-month-old boy of Caribbean/Hispanic descent, born abroad and raised in a Houston suburb, following 2 weeks in the Caribbean presented with new-onset painless gagging and vomiting multiple times per day. The emesis contained clear or partially digested food with an occasional bloody tinge. Physical examination and a barium swallow were unremarkable, and trials of ranitidine and proton-pump inhibitor (PPI) were unsuccessful. Esophagogastroduodenoscopy under general anesthesia (Figure 1a–f) revealed mild erythema throughout the distal esophagus, corpus, antrum, and fundus, with prominent antral nodularity and friability. Mild edema was present in the duodenal folds. Biopsies from the fundus (Figure 1g–h) and corpus revealed oxyntic-predominant chronic active gastritis with increased eosinophils. Antral biopsies (Figure 1i–j) revealed severe chronic active gastritis. The esophagus was unremarkable, and duodenal biopsies revealed patchy mild chronic inflammation. Gastrin was focally absent on immunostaining, and there was no evidence of granulomata, giant cells, viral inclusions, or Helicobacter pylori.

BACKGROUND To investigate the effects of patient health communication regarding their inflammatory bowel disease (IBD) to their health care providers and significant others in their daily life as a mediator in the relationship between gastrointestinal symptoms and gastrointestinal worry in pediatric patients. METHODS The Pediatric Quality of Life Inventory Gastrointestinal Symptoms, Gastrointestinal Worry, and Communication Scales, and Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-site study by 252 pediatric patients with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and patient communication were tested for bivariate and multivariate linear associations with Gastrointestinal Worry Scales specific to patient worry about stomach pain or bowel movements. Mediational analyses were conducted to test the hypothesized mediating effects of patient health communication as an intervening variable in the relationship between gastrointestinal symptoms and gastrointestinal worry. RESULTS The predictive effects of gastrointestinal symptoms on gastrointestinal worry were mediated in part by patient health communication with health care providers/significant others in their daily life. In predictive models using multiple regression analyses, the full conceptual model of demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and patient communication significantly accounted for 46, 43, and 54 percent of the variance in gastrointestinal worry (all Ps < 0.001), respectively, reflecting large effect sizes. CONCLUSIONS Patient health communication explains in part the effects of gastrointestinal symptoms on gastrointestinal worry in pediatric patients with IBD. Supporting patient disease-specific communication to their health care providers and significant others may improve health-related quality of life for pediatric patients with IBD.

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

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.