Low Vitamin D Levels in Patients with Symptoms of Gastroparesis: Relationships with Nausea and Vomiting, Gastric Emptying and Gastric Myoelectrical Activity.

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied. AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp. METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and dysrhythmic ranges, was recorded using electrogastrography. RESULTS: Overall, vitamin D levels were low (< 30 ng/ml) in 288 of 513 (56.1%) patients with symptoms of Gp (206 of 376 (54.8%) patients with delayed gastric emptying (Gp) and 82 of 137 (59.9%) patients with symptoms of Gp and normal gastric emptying). Low vitamin D levels were associated with increased nausea and vomiting (P < 0.0001), but not with fullness or bloating subscores. Low vitamin D levels in patients with Gp were associated with greater meal retention at four hours (36% retention) compared with Gp patients with normal vitamin D levels (31% retention; P = 0.05). Low vitamin D in patients with normal gastric emptying was associated with decreased normal 3 cpm GMA before (P = 0.001) and increased tachygastria after WLST (P = 0.01). CONCLUSIONS: Low vitamin D levels are present in half the patients with symptoms of gastroparesis and are associated with nausea and vomiting and gastric neuromuscular dysfunction.

Expert review of child and caregiver critiques of a therapeutic guided imagery therapy mobile application targeting disorders of gut-brain interaction in children.

Background: A guided imagery therapy mobile application (GIT App) is a novel platform for treating children with disorders of gut-brain interaction (DGBI). Previous feedback from child/caregiver dyads suggested modifications for our App prototype. However, their feedback had the potential to affect the intervention's efficacy. Thus, we aimed to have their critiques vetted by relevant experts prior to further App refinement. Objective: Compare expert reviews of the GIT App with end-users' (i.e., child/caregiver dyads') feedback. Methods: This mixed-methods study with experts included a hands-on App evaluation, a survey assessing usability, and focus groups comparing their perspectives with those previously provided by end-users. Results: Eight medical and technology experts were enrolled. Their average usability survey score of the GIT App was 69.0 ± 27.7, which was marginally above the 50th percentile. While the expert and end-user usability assessments were generally favorable, both groups agreed that the App's reminder notification feature location was not intuitive, detracting from its usability. Experts agreed with end-users that the App's aesthetics were acceptable and suggested increasing icon and font sizes. Like the end-users, the experts did not achieve consensus regarding the ideal session length or inclusion of background sounds and screen animations. Lastly, the experts agreed with end-users that gamification techniques (e.g., gift cards and virtual badges) would promote user engagement. Conclusion: An expert review of our therapeutic App revealed findings consistent with end-users and provided insight for modifying the interface and GIT sessions. Based on this experience, we recommend expert vetting of end-user suggestions as a routine checkpoint when developing therapeutic Apps.

Avoidant/restrictive food intake disorder prevalence is high in children with gastroparesis and functional dyspepsia.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) prevalence in children with gastroparesis (Gp) and/or functional dyspepsia (FD) is unknown. We aimed to identify ARFID prevalence and trajectory over 2 months in children with Gp, FD, and healthy children (HC) using two screening questionnaires. We also explored the frequency of a positive ARFID screen between those with/without delayed gastric emptying or abnormal fundic accommodation. METHODS: In this prospective longitudinal study conducted at an urban tertiary care hospital, patients ages 10-17 years with Gp or FD and age- and gender-matched HC completed two validated ARFID screening tools at baseline and 2-month follow-up: the Nine Item ARFID Screen (NIAS) and the Pica, ARFID, and Rumination Disorder Interview-ARFID Questionnaire (PARDI-AR-Q). Gastric retention and fundic accommodation (for Gp and FD) were determined from gastric emptying scintigraphy. KEY RESULTS: At baseline, the proportion of children screening positive for ARFID on the NIAS versus PARDI-AR-Q was Gp: 48.5% versus 63.6%, FD: 66.7% versus 65.2%, HC: 15.3% versus 9.7%, respectively; p < 0.0001 across groups. Of children who screened positive at baseline and participated in the follow-up, 71.9% and 53.3% were positive 2 months later (NIAS versus PARDI-AR-Q, respectively). A positive ARFID screen in Gp or FD was not related to the presence/absence of delayed gastric retention or abnormal fundic accommodation. CONCLUSIONS & INFERENCES: ARFID detected from screening questionnaires is highly prevalent among children with Gp and FD and persists for at least 2 months in a substantial proportion of children. Children with these disorders should be screened for ARFID.

Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis.

Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis.

Sex-Dependent Efficacy of Dietary Fiber in Pediatric Functional Abdominal Pain.

BACKGROUND & AIMS: Functional abdominal pain disorders (FAPDs) are more prevalent in female patients. Dietary fiber may alleviate FAPD symptoms; however, whether this effect is sex dependent remains unclear. We investigated the sex dependency of dietary fiber benefit on abdominal pain in children with FAPDs and explored the potential involvement of the gut microbiome. METHODS: In 2 cross-sectional cohorts of children with FAPDs (n = 209) and healthy control individuals (n = 105), we correlated dietary fiber intake with abdominal pain symptoms after stratifying by sex. We also performed sex-stratified and sex-interaction analyses on data from a double-blind trial in children with irritable bowel syndrome randomized to psyllium fiber (n = 39) or placebo (n = 49) for 6 weeks. Shotgun metagenomics was used to investigate gut microbiome community changes potentially linking dietary fiber intake with abdominal pain. RESULTS: In the cross-sectional cohorts, fiber intake inversely correlated with pain symptoms in boys (pain episodes: r = -0.24, P = .005; pain days: r = -0.24, P = 0.004) but not in girls. Similarly, in the randomized trial, psyllium fiber reduced the number of pain episodes in boys (P = .012) but not in girls. Generalized linear regression models confirmed that boys treated with psyllium fiber had greater reduction in pain episodes than girls (P = .007 for fiber × sex × time interaction). Age, sexual development, irritable bowel syndrome subtype, stool form, and microbiome composition were not significant determinants in the dietary fiber effects on pain reduction. CONCLUSIONS: Dietary fiber preferentially reduces abdominal pain frequency in boys, highlighting the importance of considering sex in future dietary intervention studies for FAPDs. (ClincialTrials.gov, Number NCT00526903).

Genetic Variants in Carbohydrate Digestive Enzyme and Transport Genes Associated with Risk of Irritable Bowel Syndrome.

Irritable Bowel Syndrome (IBS) is characterized by abdominal pain and alterations in bowel pattern, such as constipation (IBS-C), diarrhea (IBS-D), or mixed (IBS-M). Since malabsorption of ingested carbohydrates (CHO) can cause abdominal symptoms that closely mimic those of IBS, identifying genetic mutations in CHO digestive enzymes associated with IBS symptoms is critical to ascertain IBS pathophysiology. Through candidate gene association studies, we identify several common variants in TREH, SI, SLC5A1 and SLC2A5 that are associated with IBS symptoms. By investigating rare recessive Mendelian or oligogenic inheritance patterns, we identify case-exclusive rare deleterious variation in known disease genes (SI, LCT, ALDOB, and SLC5A1) as well as candidate disease genes (MGAM and SLC5A2), providing potential evidence of monogenic or oligogenic inheritance in a subset of IBS cases. Finally, our data highlight that moderate to severe IBS-associated gastrointestinal symptoms are often observed in IBS cases carrying one or more of deleterious rare variants.

A pilot genome-wide association study meta-analysis of gastroparesis.

BACKGROUND: Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. OBJECTIVE: Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed. METHODS: We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls. RESULTS: While no SNP associations were detected at strict significance (p ≤ 5 × 10-8 ), nine independent genomic loci were associated at suggestive significance (p ≤ 1 × 10-5 ), with the strongest signal (rs9273363, odds ratio = 1.4, p = 1 × 10-7 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (pFDR ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta = 0.13, p = 0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r = 0.8, p = 0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p = 0.005 vs. controls). CONCLUSION: We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.

Factors Associated With Adherence to a Low Fermentable Carbohydrate Diet in Children With Functional Gastrointestinal Disorders.

BACKGROUND: The low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet (LFD) has been associated with reduced symptomology in pediatric functional gastrointestinal disorders (FGIDs). The LFD is a complex dietary intervention that may be difficult to follow; thus, there is great interest in determining factors that contribute to adherence. OBJECTIVE: To examine whether baseline abdominal pain, emotional/behavioral problems, or quality of life predict adherence to the LFD in children with FGIDs. DESIGN: This was a single-group pre-post intervention design within a larger randomized controlled trial. PARTICIPANTS/SETTING: Thirty 7- to 12-year-old children with FGIDs were recruited from pediatric gastrointestinal and primary care settings throughout Texas from 2019 to 2021. Evaluated participants were randomized to an LFD intervention as part of a larger randomized controlled trial. INTERVENTION: Participants received dietary counseling and followed the LFD for 3 weeks. MEASURES: Emotional or behavioral problems and quality of life were obtained via parent report, and abdominal pain was measured via child report. Adherence was assessed by using diet records and computed by a decrease in consumption of overall FODMAP intake. STATISTICAL ANALYSES PERFORMED: A hierarchical generalized linear mixed regression model examined factors associated with adherence. RESULTS: Greater baseline quality of life was associated with better adherence to the LFD (beta coefficient ß = -.02, P = 0.03), and baseline emotional/behavioral problems and abdominal pain complaints were not significantly associated with adherence (all Ps > 0.28). CONCLUSIONS: Higher child quality of life as reported by parents was related to increased adherence to this complex dietary intervention.

Donor-recipient specificity and age-dependency in fecal microbiota therapy and probiotic resolution of gastrointestinal symptoms.

Fecal microbiota transplantation (FMT) has proven to be an effective treatment for recurrent Clostridioides difficile infection (rCDI) in both adult and pediatric patients. However, as microbiome development is a critical factor in children, it remains unclear whether adult fecal donors can provide age-appropriate functional restoration in pediatric patients. To address this issue, we conducted an integrated systems approach and found that concordant donor strain engraftment, along with metabolite restoration, are associated with FMT outcomes in both adult and pediatric rCDI patients. Although functional restoration after FMT is not strain-specific, specialized metabolic functions are retained in pediatric patients when adult fecal donors are used. Furthermore, we demonstrated broad utility of high-resolution variant-calling by linking probiotic-strain engraftment with improved gastrointestinal symptoms in adults with irritable bowel syndrome and in children with autism spectrum disorder. Our findings emphasize the importance of strain-level identification when assessing the efficacy of probiotics and microbiota-based therapeutics.

Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis.

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD0)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD0 and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis underwent GES to obtain gastric retention and IMD0, WLST, and filled out patient assessment of upper GI symptoms. A total of 234 patients with symptoms of gastroparesis were assessed (86 patients with diabetes, 130 idiopathic, 18 postfundoplication) and 175 (75%) delayed gastric emptying. Low IMD0 <0.568 suggesting initial rapid transit to the distal stomach was present in 8% and correlated with lower gastric retention, less heartburn, and lower volumes consumed during WLST. Low WLST volume (<238 mL) was present in 20% and associated with increased severity of early satiety, postprandial fullness, loss of appetite, and nausea. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. Thus, IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.NEW & NOTEWORTHY IMD0 and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.

Many pediatric patients with gastroparesis do not receive dietary education.

BACKGROUND: Gastroparesis is delayed gastric emptying in the absence of obstruction; dietary modifications are first-line treatment. However, we do not know the factors related to provision of dietary recommendations. METHODS: We sought to determine how often pediatric patients with gastroparesis receive dietary education (from a gastroenterology provider vs dietitian), the recommendations given, and factors related to these outcomes. We performed a retrospective chart review of children 2- to 18-years-old managed by pediatric gastroenterology providers at our institution. Patient demographics and clinical data, dietary advice given (if any), and dietitian consultation (if any), practice location, and prokinetic use were captured. An adjusted binomial regression model identified factors associated with dietary education provision, dietitian consultation, and diet(s) recommended. RESULTS: Of 161 patients who met criteria, 98 (60.8%) received dietary education and 42 (26.1%) met with a dietitian. The most common recommendation by gastroenterology providers and dietitians was diet composition adjustment (26.5% and 47.6%, respectively). Patients with nausea/vomiting were less likely to receive dietary education or be recommended to adjust diet composition. Patients with weight loss/failure to thrive were more likely to receive dietitian support. Patients seen in the community vs medical center outpatient setting were more likely to be recommended a low-fat diet. CONCLUSIONS: Only a little over half of children with gastroparesis receive dietary education and use of a dietitian's expertise is much less frequent. Symptoms and clinical setting appear related to what, where, and by whom guidance is provided.

Age Differences in Core Symptoms and Symptom Relationships in Patients With Irritable Bowel Syndrome: A Network Analysis.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterized by symptoms of abdominal pain and changes in bowel habits. It often co-occurs with extraintestinal somatic and psychological symptoms. However, the nature of the interrelationships among these symptoms is unclear. Although previous studies have noted age differences in IBS prevalence and specific symptom severity, it remains unknown whether specific symptoms and symptom relationships may differ by age. METHODS: Symptom data were collected in 355 adults with IBS (mean age 41.4 years, 86.2% female). Network analysis was used to examine the interrelationships among 28 symptoms and to identify the core symptoms driving the symptom structure between young (≤45 years) vs older (>45 years) adults with IBS. We evaluated 3 network properties between the 2 age groups: network structure, edge (connection) strength, and global strength. RESULTS: In both age groups, fatigue was the top core symptom. Anxiety was a second core symptom in the younger age group, but not the older age group. Intestinal gas and/or bloating symptoms also exerted considerable influences in both age groups. The overall symptom structure and connectivity were found to be similar regardless of age. DISCUSSION: Network analysis suggests fatigue is a critical target for symptom management in adults with IBS, regardless of age. Comorbid anxiety is likely an important treatment focus for young adults with IBS. Rome V criteria update could consider the importance of intestinal gas and bloating symptoms. Additional replication with larger diverse IBS cohorts is warranted to verify our results.

Gastrointestinal Symptoms Profile in Gastroparesis Compared to Other Functional and Organic Gastrointestinal Diseases.

OBJECTIVES: The primary objective was to compare the patient-reported gastrointestinal symptoms profiles of pediatric patients with gastroparesis to pediatric patients with 1 of 7 other functional gastrointestinal disorders and organic gastrointestinal diseases using the Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Scales. METHODS: The gastrointestinal symptoms profiles of 64 pediatric patients with gastroparesis who manifested abnormal gastric retention based on gastric emptying scintigraphy testing were compared to 582 pediatric patients with 1 of 7 physician-diagnosed gastrointestinal disorders (functional abdominal pain, irritable bowel syndrome, functional dyspepsia, gastroesophageal reflux disease, functional constipation, Crohn disease, ulcerative colitis). 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, with an overall total gastrointestinal symptoms score. RESULTS: The gastrointestinal symptoms profile analysis identified significantly worse overall total gastrointestinal symptoms scores between pediatric patients with gastroparesis compared to all other gastrointestinal groups except for irritable bowel syndrome (most P s < 0.001), with significant differences for stomach discomfort when eating compared to all 7 other gastrointestinal groups (most P s < 0.001). Nausea and vomiting were significantly worse for gastroparesis compared to all other gastrointestinal groups except for functional dyspepsia (all P s < 0.001). CONCLUSIONS: Pediatric patients with gastroparesis self-reported significantly worse overall total gastrointestinal symptoms compared to all other gastrointestinal diagnostic groups except for irritable bowel syndrome, with stomach discomfort when eating and nausea and vomiting symptoms exhibiting the greatest differences compared to most gastrointestinal diagnostic groups.

Children's and Caregivers' Review of a Guided Imagery Therapy Mobile App Designed to Treat Children With Functional Abdominal Pain Disorders: Leveraging a Mixed Methods Approach With User-Centered Design.

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.

Characteristics and outcomes of patients with gastroparesis using enteral and/or exclusive parenteral nutrition.

BACKGROUND: Patients with gastroparesis (Gp) may need enteral nutrition (EN) or exclusive parenteral nutrition (PN). Among patients with Gp, we aimed to (1) identify the frequency of EN and exclusive PN use and (2) explore characteristics of patients using EN and/or exclusive PN compared with those using oral nutrition (ON), including changes over 48 weeks. METHODS: Patients with Gp underwent history and physical examination, gastric emptying scintigraphy, water load satiety testing (WLST), and questionnaires assessing gastrointestinal symptoms and quality of life (QOL). Patients were observed 48 weeks. RESULTS: Of 971 patients with Gp (idiopathic, 579; diabetic, 336; post-Nissen fundoplication, 51), 939 (96.7%) were using ON only, 14 (1.4%) using exclusive PN, and 18 (1.9%) using EN. Compared with patients receiving ON, patients receiving exclusive PN and/or EN were younger, had lower body mass index, and had greater symptom severity. Patients receiving exclusive PN and/or EN had lower physical QOL but not mental QOL or Gp-related QOL scores. Patients receiving exclusive PN and/or EN ingested less water during WLST but did not have worse gastric emptying. Of those who had been receiving exclusive PN and/or EN, 50% and 25%, respectively, resumed ON at 48-week follow-up. CONCLUSIONS: This study describes patients with Gp requiring exclusive PN and/or EN for nutrition support, who represent a small (3.3%) but important subset of patients with Gp. Unique clinical and physiological parameters are associated with this subset and provide insight into the use of nutrition support in Gp.

Exploration of associations among dietary tryptophan, microbiome composition and function, and symptom severity in irritable bowel syndrome.

BACKGROUND: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS. METHODS: Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and quantitative measurement of TRP by mass spectrometry. RESULTS: Our cohort included 115 females, 69 with IBS and 46 HCs, with a mean age of 28.5 years (SD 7.4). TRP intake (p = 0.71) and stool TRP level (p = 0.27) did not differ between IBS and HC. Bifidobacterium abundance was lower in the IBS group than in HCs (p = 0.004). Predicted TRP metabolism gene content was higher in IBS than HCs (FDR-corrected q = 0.006), whereas predicted biosynthesis gene content was lower (q = 0.045). Within the IBS group, there was no association between symptom severity and TRP intake or stool TRP, but there was a significant interaction between Bifidobacterium abundance and TRP intake (q = 0.029) in predicting stool character. CONCLUSIONS: Dietary TRP intake, microbiome composition, and differences in TRP metabolism constitute a complex interplay of factors that could modulate IBS symptom severity.

Effect of liquid and solid test meals on symptoms and gastric myoelectrical activity in patients with gastroparesis and functional dyspepsia.

BACKGROUND: Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain. AIMS: To compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Infant behavioral state and stool microbiome in infants receiving Lactocaseibacillus rhamnosus GG in formula: randomized controlled trial.

BACKGROUND: Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG). METHODS: In this single-center, double-blind, controlled, parallel, prospective study, term infants (14-28 days of age) identified with colic (using modified Wessel's criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow's milk-based infant formula (PHF, n = 35) or a similar formula with added LGG (PHF-LGG, n = 36). Parent-reported infant behavior was recorded at three time points (Study Days 2-4, 10-12, and 18-20). Duration (hours/day) of crying/fussing (averaged over each three-day period) was the primary outcome. Stool samples were collected at Baseline and Study End (Days 19-21) to determine stool LGG colonization (by qPCR) and microbial abundance (using 16S rRNA gene sequencing) and calprotectin (µg/g). RESULTS: Duration of crying/fussing (mean ± SE) decreased and awake/content behavior increased over time with no significant group differences over the course of the study. There were no group differences in the percentage of infants who experienced colic by study end. Colic decreased by Study End vs Baseline in both groups. Change in fecal calprotectin also was similar between groups. Comparing Study End vs Baseline, LGG abundance was greater in the PHF-LGG group (P < 0.001) whereas alpha diversity was greater in the PHF group (P = 0.022). Beta diversity was significantly different between PHF and PHF-LGG at Study End (P = 0.05). By study end, relative abundance of L. rhamnosus was higher in the PHF-LGG vs PHF group and vs Baseline. CONCLUSIONS: In this pilot study of infants with colic, both study formulas were well tolerated. Crying/fussing decreased and awake/content behavior increased in both study groups over the course of the study. Study results demonstrate a successful introduction of the probiotic to the microbiome. The partially hydrolyzed protein formula with added LGG was associated with significant changes in the gut microbiome. TRIAL REGISTRATION: ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT02340143 . Registered 16/01/2015.