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Gastroparesis (Gp) is a delay in gastric emptying in the absence of a mechanical obstruction and has the capacity to cause symptoms that significantly impact a patient's quality of life. Dietary interventions are the first-line treatment in Gp, but the efficacy of different diets is unclear. This systematic review seeks to determine the effectiveness of dietary interventions on clinical outcomes in Gp. A literature search of MEDLINE Ovid from 1 March 2008 to 1 October 2021 was conducted to identify randomized controlled trials, cohort studies, and cross-sectional studies that reported dietary interventions in Gp. From the initial search, 2789 studies resulted. These were assessed by 2 independent reviewers and selected based on the primary outcomes of interest: changes in symptom-specific patient-reported outcomes and changes in gastric emptying time. A third reviewer resolved any discrepancies. Six adult studies (185 subjects) met the inclusion criteria, whereas no pediatric study did. Five of the included studies were randomized controlled trials and one was an observational study. The systematic review suggested low-fat diets, small-particle diets, diets with isoflavones, and foods considered bland, starchy, sweet, and salty did not exacerbate Gp symptoms. Small-particle diets and diets with isoflavones were found to improve gastric emptying time in patients. Additionally, small-particle diets were shown to reduce anxiety in comparison to large-particle diets. Of the randomized controlled trials, 80% were low risk of bias and 20% were fair risk of bias. The observational study was considered fair quality. The data presented in this review suggest specific dietary interventions could potentially improve Gp symptoms and gastric emptying in adult patients, particularly low-fat and small-particle diets. For pediatric Gp, data are lacking. The limited data available highlights a critical gap in the literature.

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 characterize the types of multisite pain experienced by children with functional abdominal pain disorders (FAPDs) and to examine differences in psychosocial distress, functional disability and health-related quality of life in children with multisite pain vs. abdominal pain alone. STUDY DESIGN: Cross-sectional study of children ages 7-17 years (n=406) with pediatric Rome III FAPDs recruited from both primary and tertiary care between January 2009 and June 2018. Subjects completed 14-day pain and stool diaries, as well as validated questionnaires assessing abdominal and non-abdominal pain symptoms, anxiety, depression, functional disability and health-related quality of life. RESULTS: 295 (73%) children endorsed at least one co-occurring non-abdominal pain thus were categorized as having multisite pain with the following symptoms: 172 (42%) headaches, 143 (35%) chest pain, 134 (33%) muscle soreness, 110 (27%) back pain, 94 (23%) joint pain, and 87 (21%) extremity (arms and legs) pain. In addition, 200 children (49%) endorsed two or more non-abdominal pain symptoms. Participants with (vs without) multisite pain had significantly higher abdominal pain frequency (P

BACKGROUND Functional abdominal pain disorders (FAPDs) are highly prevalent and associated with substantial morbidity. Guided imagery therapy (GIT) is efficacious; however, barriers often impede patient access. Therefore, we developed a GIT mobile app as a novel delivery platform. OBJECTIVE Guided by user-centered design, this study captured the critiques of our GIT app from children with FAPDs and their caregivers. METHODS Children aged 7 to 12 years with Rome IV–defined FAPDs and their caregivers were enrolled. The participants completed a software evaluation, which assessed how well they executed specific app tasks: opening the app, logging in, initiating a session, setting the reminder notification time, and exiting the app. Difficulties in completing these tasks were tallied. After this evaluation, the participants independently completed a System Usability Scale survey. Finally, the children and caregivers were separately interviewed to capture their thoughts about the app. Using a hybrid thematic analysis approach, 2 independent coders coded the interview transcripts using a shared codebook. Data integration occurred after the qualitative and quantitative data were analyzed, and the collective results were summarized. RESULTS We enrolled 16 child-caregiver dyads. The average age of the children was 9.0 (SD 1.6) years, and 69% (11/16) were female. The System Usability Scale average scores were above average at 78.2 (SD 12.6) and 78.0 (SD 13.5) for the children and caregivers, respectively. The software evaluation revealed favorable usability for most tasks, but 75% (12/16) of children and 69% (11/16) of caregivers had difficulty setting the reminder notification. The children’s interviews confirmed the app’s usability as favorable but noted difficulty in locating the reminder notification. The children recommended adding exciting scenery and animations to the session screen. Their preferred topics were animals, beaches, swimming, and forests. They also recommended adding soft sounds related to the session topic. Finally, they suggested that adding app gamification enhancements using tangible and intangible rewards for listening to the sessions would promote regular use. The caregivers also assessed the app’s usability as favorable but verified the difficulty in locating the reminder notification. They preferred a beach setting, and theme-related music and nature sounds were recommended to augment the session narration. App interface suggestions included increasing the font and image sizes. They also thought that the app’s ability to relieve gastrointestinal symptoms and gamification enhancements using tangible and intangible incentives would positively influence the children’s motivation to use the app regularly. Data integration revealed that the GIT app had above-average usability. Usability challenges included locating the reminder notification feature and esthetics affecting navigation. CONCLUSIONS Children and caregivers rated our GIT app’s usability favorably, offered suggestions to improve its appearance and session content, and recommended rewards to promote its regular use. Their feedback will inform future app refinements.

Background Functional abdominal pain disorders (FAPDs) are highly prevalent and associated with substantial morbidity. Guided imagery therapy (GIT) is efficacious; however, barriers often impede patient access. Therefore, we developed a GIT mobile app as a novel delivery platform. Objective Guided by user-centered design, this study captured the critiques of our GIT app from children with FAPDs and their caregivers. Methods Children aged 7 to 12 years with Rome IV–defined FAPDs and their caregivers were enrolled. The participants completed a software evaluation, which assessed how well they executed specific app tasks: opening the app, logging in, initiating a session, setting the reminder notification time, and exiting the app. Difficulties in completing these tasks were tallied. After this evaluation, the participants independently completed a System Usability Scale survey. Finally, the children and caregivers were separately interviewed to capture their thoughts about the app. Using a hybrid thematic analysis approach, 2 independent coders coded the interview transcripts using a shared codebook. Data integration occurred after the qualitative and quantitative data were analyzed, and the collective results were summarized. Results We enrolled 16 child-caregiver dyads. The average age of the children was 9.0 (SD 1.6) years, and 69% (11/16) were female. The System Usability Scale average scores were above average at 78.2 (SD 12.6) and 78.0 (SD 13.5) for the children and caregivers, respectively. The software evaluation revealed favorable usability for most tasks, but 75% (12/16) of children and 69% (11/16) of caregivers had difficulty setting the reminder notification. The children’s interviews confirmed the app’s usability as favorable but noted difficulty in locating the reminder notification. The children recommended adding exciting scenery and animations to the session screen. Their preferred topics were animals, beaches, swimming, and forests. They also recommended adding soft sounds related to the session topic. Finally, they suggested that adding app gamification enhancements using tangible and intangible rewards for listening to the sessions would promote regular use. The caregivers also assessed the app’s usability as favorable but verified the difficulty in locating the reminder notification. They preferred a beach setting, and theme-related music and nature sounds were recommended to augment the session narration. App interface suggestions included increasing the font and image sizes. They also thought that the app’s ability to relieve gastrointestinal symptoms and gamification enhancements using tangible and intangible incentives would positively influence the children’s motivation to use the app regularly. Data integration revealed that the GIT app had above-average usability. Usability challenges included locating the reminder notification feature and esthetics affecting navigation. Conclusions Children and caregivers rated our GIT app’s usability favorably, offered suggestions to improve its appearance and session content, and recommended rewards to promote its regular use. Their feedback will inform future app refinements.

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

The primary objective was to compare the patient-reported gastrointestinal symptoms profiles of pediatric patients with gastroparesis to matched healthy controls using the Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales. The secondary objectives were to compare pediatric patients with gastroparesis to pediatric patients with gastroparesis-like symptoms and normal gastric emptying and to compare pediatric patients with gastroparesis-like symptoms and normal gastric emptying to matched healthy controls.The PedsQL™ Gastrointestinal Symptoms Scales were completed by 64 pediatric patients with gastroparesis, 59 pediatric patients with gastroparesis-like symptoms and normal gastric emptying, and 200 age, gender, and race/ethnicity matched healthy controls. The PedsQL™ Gastrointestinal Symptoms Scales encompass 10 individual multi-item scales which measure 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/fecal incontinence. Based on gastric emptying scintigraphy testing, those with abnormal gastric retention were classified as having gastroparesis.The gastrointestinal symptoms profile analysis identified large differences between those with gastroparesis compared to healthy controls (most P0.001), with the largest effect sizes for upper gastrointestinal symptoms including stomach pain, stomach discomfort when eating, food and drink limits, nausea, and vomiting. Those with gastroparesis self-reported similar gastrointestinal symptoms to those with normal gastric emptying, except for increased constipation.Pediatric patients with gastroparesis self-reported broad multidimensional gastrointestinal symptoms profiles in comparison to healthy controls with large differences, indicating the critical need for more highly efficacious interventions to bring patient functioning within the normal range of healthy functioning.

Patients often are evaluated for gastroparesis because of symptoms occurring with meals. Gastric emptying scintigraphy (GES) is used for gastroparesis diagnosis, although results are not well correlated with gastroparesis symptoms. The aim of this study is to assess relationships between gastroparesis symptoms, gastric emptying (GE), and gastric accommodation (GA). Patients with symptoms of gastroparesis completed the Patient Assessment of Upper GI Symptoms (PAGI-SYM) and recorded symptoms during GES and water load satiety test (WLST), an indirect assessment for GA. A total of 109 patients with gastroparesis symptoms were assessed. Symptom severity increased after GES meal for stomach fullness, belching, nausea, abdominal burning, and abdominal pain. There was no difference in symptoms after meal between patients with delayed (n = 66) and normal (n = 42) GE. Diabetic patients (n = 26) had greater gastric retention than idiopathic patients (n = 78), but idiopathic patients had greater postprandial nausea, stomach fullness, and abdominal pain. Water consumed during WLST averaged 421 ± 245 mL. Idiopathic patients had greater nausea scores during WLST than diabetic patients. In comparison to those with normal water consumption (≥238 mL; n = 80), patients with impaired water ingestion (

Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain.To compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD.Patients enrolled in the Gastroparesis Clinical Research Consortium Registry were studied. Clinical characteristics were measured with standard questionnaires. GP was determined by 4-h solid-phase gastric scintigraphy. GMA was measured using electrogastrography before and after ingestion of a water load or nutrient bar on separate days. Symptoms were measured on visual analog scales. GMA responses to the water load for individual patients were also determined.284 patients with GP and 113 with FD were identified who ingested both test meals. Patients with GP and FD had similar maximal tolerated volumes of water [mean (SD) 378 (218) ml vs. 402 (226) ml, p = 0.23] and reported similar intensity of fullness, nausea, bloating, and abdominal discomfort after the test meals. Twenty-six percent and 19% of the patients with GP and FD, respectively, ingested subthreshold (238 ml) volumes of water (p = 0.15). Gastric dysrhythmias were recorded in 66% of the GP and 65% of the FD patients after the water load. Symptoms and GMA were similar in both groups after ingestion of the nutrient bar.The similarity in GMA responses and symptoms after ingestion of solid or liquid test meals suggests GP and FD are closely related gastric neuromuscular disorders.

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

We sought to determine how a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet (LFD) affected high FODMAP food intake, nutrient intake, and diet quality in children with functional abdominal pain disorders (FAPD).Children (ages 7-13 years) with Rome IV FAPD began a dietitian-guided LFD. Three-day food records were captured at baseline and 2-3 weeks into the LFD. Intake of high FODMAP foods, energy, macronutrients, micronutrients, food groups, and ultra-processed foods were determined.Median age of participants was 11 years, and 19/31 (61%) were female. Twenty-eight (90%) decreased high FODMAP food intake on the LFD: overall median (25-75%) high FODMAP foods/day decreased from 5.7 (3.6-7.3) to 2 (0.3-3.7) (p 0.001). A more adherent subset (n = 22/71%) of participants consumed on average ≤3 high FODMAP foods per day during the LFD. Baseline nutritional intake and quality were generally poor with several micronutrient deficiencies identified. Diet quality improved on the LFD with increased servings of vegetables and protein and decreased consumption of ultra-processed foods, trans-fatty acids, and added sugars. On the LFD, there were significant decreases in total carbohydrates and thiamin (remained within recommended intake) and significant increases in vitamin B6 (p = 0.029), vitamin C (p = 0.019), and vitamin E (p = 0.009). Children more adherent to the LFD further increased vitamin D, magnesium, potassium, and fat servings.The majority of children with FAPD on a dietitian-led LFD successfully decreased high FODMAP food intake. Children with FAPD on the LFD (vs. baseline) modestly improved micronutrient intake and diet quality.

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.

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

The Gastroparesis Clinical Research Consortium is a multicenter coalition created and funded by the National Institutes of Diabetes and Digestive and Kidney Disorders, with a mission to advance understanding of the pathophysiology of gastroparesis and develop an effective treatment for patients with symptomatic gastroparesis. In this review, we summarize the results of the published Gastroparesis Clinical Research Consortium studies as a ready and convenient resource for gastroenterologists and others to provide a clear understanding of the consortium's experience and perspective on gastroparesis and related disorders.

Peppermint oil (PMO) is effective in the treatment of functional abdominal pain disorders, but its mechanism of action is unclear. Evidence suggests PMO has microbicidal activity. We investigated the effect of three different doses of PMO on gut microbiome composition. Thirty children (7-12 years of age) with functional abdominal pain provided a baseline stool sample prior to randomization to 180, 360, or 540 mg of enteric coated PMO (10 participants per dose). They took their respective dose of PMO (180 mg once, 180 mg twice, or 180 mg thrice daily) for 1 week, after which the stool collection was repeated. Baseline and post-PMO stools were analyzed for microbiome composition. There was no difference in alpha diversity of the gut microbiome between the baseline and post-PMO treatment. Principal coordinate analysis revealed no significant difference in overall bacterial composition between baseline and post-PMO samples, as well as between the PMO dose groups. However, the very low abundant Collinsella genus and three operational taxonomic units (one belonging to Collinsella) were significantly different in samples before and after PMO treatment. The Firmicutes/Bacteroidetes ratio was lower in children who received 540 mg of PMO compared to the 180 mg and 360 mg dose groups (p = 0.04). Network analysis revealed separation between pre- and post-PMO fecal samples with the genus Collinsella driving the post-PMO clusters. PMO administration appeared to impact only low abundance bacteria. The 540 mg PMO dose differentially impacted the Firmicutes/Bacteroidetes ratio. A higher dose and/or longer duration of treatment might yield different results.

BACKGROUND: The healthcare burden of pediatric functional gastrointestinal pain disorders (FGIDs) is unclear. Our study aimed to characterize the burden of these hospitalizations in the United States (US). METHODS: We utilized the US National Inpatient Sample from 2002 to 2018 to capture pediatric hospitalizations (ages 4 to 18 years old) with a primary discharge diagnosis of abdominal pain, constipation, irritable bowel syndrome, dyspepsia, abdominal migraine, cyclic vomiting syndrome, or fecal incontinence. We calculated the FGID hospitalization prevalence rate, length-of-stay (LOS), and inflation-adjusted costs annually and assessed for statistically significant trend changes using joinpoint analyses. KEY RESULTS: 22.3 million pediatric hospitalizations were captured, and 1 in 64 pediatric hospitalizations were attributed to a primary FGID hospitalization. The overall FGID hospitalization prevalence rate initially remained stable but decreased significantly from 2013 to 2018. Constipation and abdominal pain hospitalization rates, respectively, increased and decreased significantly over time. Constipation hospitalizations were more prevalent for younger non-Hispanic Blacks and Hispanics. FGID hospitalization rates stratified by sex were similar. Mean LOS was 2.3 days; average LOS increased significantly from 2002 to 2013 and then stabilized. FGID hospitalization costs averaged $6,216 per admission and increased significantly for all FGIDs except dyspepsia. Endoscopic procedures were the most common interventions. CONCLUSIONS & INFERENCES: FGID hospitalization prevalence rates decreased recently, possibly due to national healthcare policy implementation. Nonetheless, constipation admissions increased. LOS was stable in recent years but associated costs-per-hospitalization were increasing over time, probably due to endoscopic procedures. More studies are needed to explain these prevalence and cost trends.

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.

Background Gastric accommodation is an essential gastric motor function which occurs following ingestion of a meal. Impaired gastric fundic accommodation (IFA) is associated with dyspeptic symptoms. Gastric accommodation is mediated by the vagal pathway with several important physiologic factors such as duodenal nutrient feedback playing a significant role. IFA has been described as a pathophysiologic factor in several gastrointestinal disorders including functional dyspepsia, diabetic gastropathy, post-Nissen fundoplication, postsurgical gastrectomy, and rumination syndrome. Modalities for gastric accommodation assessment include gastric barostat, intragastric meal distribution via scintigraphy, drinking tests (eg, water load), SPECT, MRI, 2D and 3D ultrasound, and intragastric high-resolution manometry. Several treatment options including sumatriptan, buspirone, tandospirone, ondansetron, and acotiamide may improve symptoms by increasing post-meal gastric volume. Purpose Our aim is to provide an overview of the physiology, diagnostic modalities, and therapies for IFA. A literature search was conducted on PubMed, Google Scholar, and other sources to identify relevant studies available until December 2020. Gastric accommodation is an important gastric motor function which if impaired, is associated with several upper gastrointestinal disorders. There are an increasing number of gastric accommodation testing modalities; however, each has facets which warrant consideration. Evidence regarding potentially effective therapies for IFA is growing.

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.

OBJECTIVES: Like adults, children suffer from gastroparesis. However, there are currently no validated instruments to determine the impact of gastroparesis in pediatric patients. The objective of this study was to develop the items and domains to support the content validity of the new Pediatric Quality of Life Inventory (PedsQL(™)) Gastroparesis Symptoms Module. METHODS: Patients were recruited from the National Institute of Diabetes and Digestive and Kidney Diseases Pediatric Gastroparesis Registry. The qualitative methods involved an iterative process comprising a literature review of existing questionnaires and gastroparesis clinical research, an expert review panel of pediatric gastroenterologists who provided feedback on the conceptual framework in developing the semi-structured interview, and in-depth focus interviews with six pediatric patients with gastroparesis and five of their parents (one did not participate) in developing relevant domains and item content. In the subsequent cognitive interviews phase, five additional patients with gastroparesis and their parents provided detailed feedback on item content, relevance, importance, and understandability of the domains and items. RESULTS: Ten domains/scales were derived from the qualitative methods, with item content saturation achieved at 67 items, with no further themes or content identified during the final cognitive interviews. The Module is comprised of 10 individual scales measuring nausea, stomach fullness when eating, vomiting, dry heaves, heartburn and reflux, stomach pain and hurt, food and drink limits, bloating, appetite, and worry. CONCLUSIONS: Our study supports the content validity of the new PedsQL(™) Gastroparesis Symptoms Module. The Module field test study will be conducted in a multisite national study.

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.

The importance of gut microbiota in gastrointestinal (GI) physiology was well described, but our ability to study gut microbial ecosystems in their entirety was limited by culture-based methods prior to the sequencing revolution. The advent of high-throughput sequencing opened new avenues, allowing us to study gut microbial communities as an aggregate, independent of our ability to culture individual microbes. Early studies focused on association of changes in gut microbiota with different disease states, which was necessary to identify a potential role for microbes and generate novel hypotheses. Over the past few years the field has moved beyond associations to better understand the mechanistic implications of the microbiome in the pathophysiology of complex diseases. This movement also has resulted in a shift in our focus toward therapeutic strategies, which rely on better understanding the mediators of gut microbiota-host cross-talk. It is not surprising the gut microbiome has been implicated in the pathogenesis of functional gastrointestinal disorders given its role in modulating physiological processes such as immune development, GI motility and secretion, epithelial barrier integrity, and brain-gut communication. In this review, we focus on the current state of knowledge and future directions in microbiome research as it pertains to functional gastrointestinal disorders. We summarize the factors that help shape the gut microbiome in human beings. We discuss data from animal models and human studies to highlight existing paradigms regarding the mechanisms underlying microbiota-mediated alterations in physiological processes and their relevance in human interventions. While translation of microbiome science is still in its infancy, the outlook is optimistic and we are advancing in the right direction toward precise mechanism-based microbiota therapies.