Recent PubMed Articles on Gut Motility

Effects of Serotonin and Slow-release 5-HTP on Gastrointestinal Motility in a Mouse Model of Depression.

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Effects of Serotonin and Slow-release 5-HTP on Gastrointestinal Motility in a Mouse Model of Depression.

Gastroenterology. 2019 Apr 25;:

Authors: Israelyan N, Del Colle A, Li Z, Park Y, Xing A, Jacobsen JPR, Luna RA, Jensen DD, Madra M, Saurman V, Rahim R, Latorre R, Law K, Carson W, Bunnett NW, Caron MG, Margolis KG

Abstract
BACKGROUND & AIMS: Mood disorders and constipation are often comorbid yet their shared etiologies have rarely been explored. The neurotransmitter serotonin (5-HT) regulates central nervous system and enteric nervous system (ENS) development and long-term functions, including gastrointestinal (GI) motility and mood. Defects in neuron production of 5-HT might therefore result in brain and intestinal dysfunction. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in 5-HT biosynthesis. A variant of TPH2 that encodes the R441H substitution (TPH2-R441H) was identified in individuals with severe depression. We studied mice with an analogous mutation (TPH2-R439H), which results in a 60%-80% decrease in levels of 5-HT in central nervous system and behaviors associated with depression in humans. Feeding chow that contains 5-HTP slow release (5-HTP SR) to TPH2-R439H mice restores levels of 5-HT in the central nervous system and reduces depressive-like behaviors.
METHODS: We compared the effects of feeding chow, with or without 5-HTP SR, to mice with the TPH2-R439H mutation and without this mutation (control mice). Myenteric and submucosal plexuses were isolated from all 4 groups of mice and immunocytochemistry was used to quantify total enteric neurons, serotonergic neurons, and 5-HT-dependent subsets of neurons. We performed calcium imaging experiments to evaluate responses of enteric neurons to tryptamine-evoked release of endogenous 5-HT. In live mice we measured total GI transit, gastric emptying, small intestinal transit, and propulsive colorectal motility. To measure colonic migrating motor complexes (CMMCs), we isolated colons and constructed spatiotemporal maps along the proximo-distal length to quantify the frequency, velocity, and length of CMMCs. We measured villus height, crypt perimeter, and relative densities of enterochromaffin and enteroendocrine cells in small intestinal tissue.
RESULTS: Levels of 5-HT were significantly lower in enteric neurons from TPH2-R439H mice than from control mice. TPH2-R439H mice had abnormalities in ENS development and ENS-mediated GI functions, including reduced motility and intestinal epithelial growth. Total GI transit and propulsive colorectal motility were slower in TPH2-R439H mice than controls and CMMCs were slower and less frequent. Villus height and crypt perimeter were significantly decreased in colon tissues from TPH2-R439H mice, compared with controls. Administration of 5-HTP SR to adult TPH2-R439H mice restored 5-HT to enteric neurons and reversed these abnormalities. Adult TPH2-R439H mice given oral 5-HTP SR had normalized numbers of enteric neurons, total GI transit, and colonic motility. Intestinal tissue from these mice had normal measures of CMMCs and enteric epithelial growth CONCLUSIONS: In studies of TPH2-R439H mice, we found evidence for reduced release of 5-HT from enteric neurons that results in defects in ENS development and GI motility. Our findings indicate that neuron production of 5-HT links constipation with mood dysfunction. Administration of 5-HTP SR to mice restored 5-HT to the ENS and normalized GI motility and growth of the enteric epithelium. 5-HTP SR might be used to treat patients with intestinal dysfunction associated with low levels of 5-HT.

PMID: 31071306 [PubMed - as supplied by publisher]

LncRNA TUG1 promoted KIAA1199 expression via miR-600 to accelerate cell metastasis and epithelial-mesenchymal transition in colorectal cancer.

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LncRNA TUG1 promoted KIAA1199 expression via miR-600 to accelerate cell metastasis and epithelial-mesenchymal transition in colorectal cancer.

J Exp Clin Cancer Res. 2018 May 18;37(1):106

Authors: Sun J, Hu J, Wang G, Yang Z, Zhao C, Zhang X, Wang J

Abstract
BACKGROUND: LncRNA TUG1 has been reported to be highly expressed in CRC samples and cells and promoted metastasis by affecting EMT, indicating a poor prognosis for colorectal cancer (CRC). In this study, we determined the underlying mechanism for tumor oncogenesis of lncRNA TUG1 in CRC metastasis.
METHODS: The expressions of miR-600 and KIAA1199 in 76 CRC patients and CRC cells and CRC metastatic tissues were determined using qRT-PCR. Epithelial-mesenchymal transition (EMT)-related proteins were determined using western blot. CRC cell metastasis was assessed by colony formation, wound healing and transwell assay. Luciferase reporter gene assay was used to confirm miR-600 binding to KIAA1199 3'UTR.
RESULTS: Our data showed that lncRNA TUG1 was upregulated in CRC cells, miR-600 was downregulated in CRC tissues, cell lines and CRC metastatic tissues, and low miR-600 expression predicted a poor clinical prognosis. Overexpression of miR-600 suppressed CRC cell migration/invasion and EMT-related proteins in vitro, inhibited tumor volume and weight, and decreased the number of CRC liver metastasis in vivo. KIAA1199 was upregulated in CRC tissues, and was negatively regulated by miR-600. KIAA1199 overexpression promoted CRC cell migration and invasion, which reversed the inhibition effect of miR-600 mimic on migration and invasion of CRC cells. Moreover, TUG1 negatively regulated miR-600, and inhibition of TUG1 suppressed CRC cell migration and invasion and EMT-related proteins via regulating miR-600.
CONCLUSION: Our study proved that TUG1 promoted KIAA1199 expression to accelerate EMT and metastasis of CRC cell through inhibition of miR-600 expression.

PMID: 29776371 [PubMed - indexed for MEDLINE]

Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine.

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Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine.

Sci Rep. 2017 09 04;7(1):10322

Authors: Cao H, Liu X, An Y, Zhou G, Liu Y, Xu M, Dong W, Wang S, Yan F, Jiang K, Wang B

Abstract
Chronic constipation is a prevalent functional gastrointestinal disorder accompanied with intestinal dysbiosis. However, causal relationship between dysbiosis and constipation remains poorly understood. Serotonin transporter (SERT) is a transmembrane transport protein which re-uptakes excessive 5-hydroxytryptamine (5-HT) from effective location to terminate its physiological effects and involves in regulating gastrointestinal motility. In this study, fecal microbiota from patients with constipation and healthy controls were transplanted into the antibiotic depletion mice model. The mice which received fecal microbiota from patients with constipation presented a reducing in intestinal peristalsis and abnormal defecation parameters including the frequency of pellet expulsion, fecal weight and fecal water content. After fecal microbiota transplantation, the SERT expression in the colonic tissue was significantly upregulated, and the content of 5-HT was decreased which negatively correlated with the gastrointestinal transit time. Moverover, fecal microbiota from the mice which received fecal microbiota from patients with constipation also upregulated SERT in Caco-2 cells. Besides, this process accompanied with the decreased abundance of Clostridium, Lactobacillus, Desulfovibrio, and Methylobacterium and an increased tend of Bacteroides and Akkermansia, which also involved in the impairment of intestinal barrier after FMT. Taken together, intestinal dysbiosis may upregulate the SERT expression and contribute to the development of chronic constipation.

PMID: 28871143 [PubMed - indexed for MEDLINE]

Pediatric Intestinal Pseudo-Obstruction: Impact of Neonatal and Later Onset on Clinical and Nutritional Outcomes.

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Pediatric Intestinal Pseudo-Obstruction: Impact of Neonatal and Later Onset on Clinical and Nutritional Outcomes.

J Pediatr Gastroenterol Nutr. 2019 May 02;:

Authors: Diamanti A, Fusaro F, Caldaro T, Capriati T, Candusso M, Nobili V, Borrelli O

Abstract
OBJECTIVE: To evaluate long-term nutritional outcomes and clinical characteristics in a cohort of children with pediatric intestinal pseudo-obstruction (PIPO) at neonatal-onset (NO-PIPO) and at later-onset (LO-PIPO).
METHODS: All children fulfilling new PIPO criteria over a thirty-year period were reviewed. Baseline demographic and clinical features as well as nutritional outcomes were collected. Nutritional outcomes included overall survival, prevalence of enteral autonomy and parenteral nutrition (PN) dependency, rate of major PN complications, and growth course.
RESULTS: Forty-four patients were still alive at the end of the follow-up. Twenty-five patients (57%) achieved enteral autonomy, whilst 18 remained on PN. Among the patients requiring PN at beginning of the study-period, we found that 55% (CI 34-70) has the probability of remaining on PN at the latest follow-up. Prevalence of gastro-intestinal obstruction symptoms (p < 0.01), urinary involvement (p < 0.05), stoma placements [gastrostomy (p < 0.01), ileostomy p < 0.05) and complex gastro-intestinal surgery (p < 0.05) were significantly higher in NO-PIPO than in LO-PIPO. The number of patients requiring long-term PN (p < 0.001)and the number of PN days (p < 0.05) were significantly higher in NO-PIPO, whilst the number of patients achieving enteral autonomy was significantly higher in LO-PIPO (p < 0.05).
CONCLUSIONS: In our study we have reported the nutritional outcome of a cohort of children with PIPO over a thirty-year period showing that about 20% of patients develop irreversible intestinal failure requiring life-long PN. Nutritional and clinical outcomes seem to be influenced by the time of onset of the disease.

PMID: 31058770 [PubMed - as supplied by publisher]

Renal Function in Children on Long Term Home Parenteral Nutrition.

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Renal Function in Children on Long Term Home Parenteral Nutrition.

Front Pediatr. 2019;7:137

Authors: Messova A, Dziubak R, Köglmeier J

Abstract
Objectives: To assess renal function in pediatric intestinal failure (IF) patients on long term home parenteral nutrition (HPN). Methods: Children who received HPN for a minimum of 3 years between 2007 and 2017 were identified from the IF clinic of a large tertiary referral center. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula at discharge on HPN, after 6 months, 1, 2, and 3 years. Results: Twenty five patients (40% male) fulfilled the inclusion criteria. The indications for HPN were due to an underlying motility disorder in 56% (14/25), enteropathy in 24% (6/25), and short bowel syndrome in 20% (5/25). At the start of HPN 80% (20/25) had a normal eGFR. Four children (17%) had an abnormal eGFR. In the group of patients with normal eGFR at the start of HPN 30% (6/20) had at least one episode of decreased eGFR in the following 3 years, however there was no significant decline in eGFR at the end of the 3 year study period. Overall there was no statistically significant deterioration of eGFR in the study population (p = 0.7898). Conclusion: In our cohort of children on long term HPN no significant decline of eGFR could be demonstrated within 3 years of starting PN.

PMID: 31058118 [PubMed]

The Use of Pyridostigmine in a Child With Chronic Intestinal Pseudo-Obstruction.

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The Use of Pyridostigmine in a Child With Chronic Intestinal Pseudo-Obstruction.

Pediatrics. 2018 04;141(Suppl 5):S404-S407

Authors: Choudhury A, Rahyead A, Kammermeier J, Mutalib M

Abstract
Chronic intestinal pseudo-obstruction is a rare disorder that affects the motility of the gastrointestinal tract. It results in acute or subacute intestinal obstruction symptoms in the absence of mechanical lesion. It can lead to intestinal failure in children with significant strain on nutrition, growth, and development. There is no universally agreed protocol for management of chronic intestinal pseudo-obstruction in children, and there is wide variation in clinical practice.

PMID: 29610160 [PubMed - indexed for MEDLINE]

Is There a Role for pH Impedance Monitoring in Identifying Eosinophilic Esophagitis in Children with Esophageal Atresia?

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Is There a Role for pH Impedance Monitoring in Identifying Eosinophilic Esophagitis in Children with Esophageal Atresia?

J Pediatr. 2019 Apr 26;:

Authors: Pesce M, Krishnan U, Saliakellis E, Lopez R, Lindley KJ, Thapar N, Borrelli O

Abstract
OBJECTIVES: To evaluate clinical, endoscopic, and pH-impedance measures in a cohort of children with esophageal atresia and concomitant eosinophilic esophagitis (EoE) and compared it with disease-matched controls, to identify predictive factors for the development of EoE and esophageal stricture.
STUDY DESIGN: We reviewed 63 patients with esophageal atresia assessed for refractory upper gastrointestinal symptoms between January 2015 and September 2017 at 2 tertiary referral centers. All patients underwent upper gastrointestinal endoscopy and pH-impedance monitoring. Based on esophageal histology, patients were classified as (1) esophageal atresia without evidence of esophagitis; (2) esophageal atresia with evidence of esophagitis (including esophageal eosinophilia not meeting the criteria for EoE); (3) esophageal atresia with concomitant EoE. Age and sex matched patients with gastroesophageal reflux disease were used as disease controls.
RESULTS: The presence of atopy and peripheral eosinophilia at baseline were significantly associated with EoE (P < .05). Although there was a tendency toward an increased number of strictures in patients with esophageal atresia-EoE, this did not reach statistical significance (P = .06). Higher esophageal acid exposure time and lower baseline impedance values were significantly associated with eosinophilic infiltration (P < .05 and P < .01, respectively). Using logistic regression analysis, the presence of mucosal eosinophilia was the most predictive factor for stricture formation (P < .05).
CONCLUSIONS: A history of atopy and the presence of peripheral eosinophilia in patients with esophageal atresia are predictive factors for the development of EoE, which in turn is a predictive factor for stricture occurrence. Higher esophageal acid exposure time and lower baseline impedance are associated with esophageal eosinophilic infiltration, suggesting their value in selecting which patients with esophageal atresia should undergo endoscopic examination.

PMID: 31036410 [PubMed - as supplied by publisher]

Protection of the Ovine Fetal Gut against Ureaplasma-Induced Chorioamnionitis: A Potential Role for Plant Sterols.

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Protection of the Ovine Fetal Gut against Ureaplasma-Induced Chorioamnionitis: A Potential Role for Plant Sterols.

Nutrients. 2019 Apr 27;11(5):

Authors: van Gorp C, de Lange IH, Spiller OB, Dewez F, Cillero Pastor B, Heeren RMA, Kessels L, Kloosterboer N, van Gemert WG, Beeton ML, Stock SJ, Jobe AH, Payne MS, Kemp MW, Zimmermann LJ, Kramer BW, Plat J, Wolfs TGAM

Abstract
Chorioamnionitis, clinically most frequently associated with Ureaplasma, is linked to intestinal inflammation and subsequent gut injury. No treatment is available to prevent chorioamnionitis-driven adverse intestinal outcomes. Evidence is increasing that plant sterols possess immune-modulatory properties. Therefore, we investigated the potential therapeutic effects of plant sterols in lambs intra-amniotically (IA) exposed to Ureaplasma. Fetal lambs were IA exposed to Ureaplasma parvum (U. parvum, UP) for six days from 127 d-133 d of gestational age (GA). The plant sterols β-sitosterol and campesterol, dissolved with β-cyclodextrin (carrier), were given IA every two days from 122 d-131 d GA. Fetal circulatory cytokine levels, gut inflammation, intestinal injury, enterocyte maturation, and mucosal phospholipid and bile acid profiles were measured at 133 d GA (term 150 d). IA plant sterol administration blocked a fetal inflammatory response syndrome. Plant sterols reduced intestinal accumulation of proinflammatory phospholipids and tended to prevent mucosal myeloperoxidase-positive (MPO) cell influx, indicating an inhibition of gut inflammation. IA administration of plant sterols and carrier diminished intestinal mucosal damage, stimulated maturation of the immature epithelium, and partially prevented U. parvum-driven reduction of mucosal bile acids. In conclusion, we show that β-sitosterol and campesterol administration protected the fetus against adverse gut outcomes following UP-driven chorioamnionitis by preventing intestinal and systemic inflammation.

PMID: 31035616 [PubMed - in process]

Low FODMAPs diet for functional abdominal pain disorders in children: critical review of current knowledge.

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Low FODMAPs diet for functional abdominal pain disorders in children: critical review of current knowledge.

J Pediatr (Rio J). 2019 Apr 24;:

Authors: Pensabene L, Salvatore S, Turco R, Tarsitano F, Concolino D, Baldassarre ME, Borrelli O, Thapar N, Vandenplas Y, Staiano A, Saps M

Abstract
OBJECTIVE: Over the last years, considerable efforts have been made to clarify the role of low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) diet for the treatment of functional gastrointestinal disorders (FGIDs). This narrative review aimed to provide practitioners a synthesis of the current knowledge on the role of a low FODMAPs (LFM) diet in reducing symptoms associated with functional abdominal pain disorders (FAPDs) in children. This review is focused on the pathophysiology, efficacy, and criticism of LFM in children.
SOURCES: The Cochrane Database, PubMed, and Embase were searched using specific terms for FODMAPs diet interventions and FAPDs.
SUMMARY OF THE FINDINGS: In children, only one randomized control trial and one open-label study reported positive results for the LFM diet; one randomized control trial showed exacerbation of symptoms with fructans in children with irritable bowel syndrome; no effect was found for the lactose-free diet, whilst fructose-restricted diets were effective in 5/6 studies.
CONCLUSIONS: In children there are few trials evaluating LFM in FAPDs, with encouraging data on the therapeutic efficacy, particularly regarding the fructose-restricted diet. Additional efforts are still needed to fill this research gap and clarify the most efficient way for tailoring dietary restrictions based on the patient's tolerance and/or identification of the potential biomarkers of LFM efficacy, to maintain nutritional adequacy and to simplify the adherence to diet by labeling FODMAP content in commercial products.

PMID: 31028745 [PubMed - as supplied by publisher]

Spatial Patterns From High-Resolution Electrogastrography Correlate With Severity of Symptoms in Patients With Functional Dyspepsia and Gastroparesis.

Spatial Patterns From High-Resolution Electrogastrography Correlate With Severity of Symptoms in Patients With Functional Dyspepsia and Gastroparesis.

Clin Gastroenterol Hepatol. 2019 Apr 19;:

Authors: Gharibans AA, Coleman TP, Mousa H, Kunkel DC

Abstract
BACKGROUND & AIMS: Invasive gastric electrical mapping has revealed spatial abnormalities of the slow wave in subjects with gastroparesis and functional gastrointestinal disorders. Cutaneous high-resolution electrogastrography (HR-EGG) is a non-invasive method that can detect spatial features of the gastric slow wave. We performed HR-EGG in subjects with active foregut symptoms to evaluate associations between gastric myoelectric abnormalities, symptoms (based on a validated questionnaire), and gastric emptying.
METHODS: We performed a case-control study of 32 subjects, including 7 healthy individuals (controls), 7 subjects with functional dyspepsia and normal gastric emptying, and 18 subjects with gastroparesis, from a tertiary care program. All subjects were assessed by computed tomography imaging of the abdomen and HR-EGG and completed the PAGI-SYM questionnaire on foregut symptoms, which includes the gastroparesis cardinal symptom index. We performed volume reconstruction of the torso and stomach from computed tomography images to guide accurate placement of the HR-EGG array.
RESULTS: Spatial slow-wave abnormalities were detected in 44% of subjects with foregut symptoms. Moreover, subjects with a higher percentage of slow waves with aberrant propagation direction had a higher total gastroparesis cardinal symptom index score (r = 0.56, P<.001) and more severe abdominal pain (r = 0.46, P=.009). We found no correlation between symptoms and traditional EGG parameters.
CONCLUSIONS: In case-control study, we found that the genesis of symptoms of functional dyspepsia and gastroparesis is likely multifactorial, including possible contribution from gastric myoelectric dysfunction. Abnormal spatial parameters, detected by cutaneous HR-EGG, correlated with severity of upper gastrointestinal symptoms, regardless of gastric emptying. This noninvasive, repeatable approach might be used to identify patients for whom gastric myoelectric dysfunction contributes to functional dyspepsia and gastroparesis.

PMID: 31009794 [PubMed - as supplied by publisher]

Oesophageal atresia.

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Oesophageal atresia.

Nat Rev Dis Primers. 2019 Apr 18;5(1):26

Authors: van Lennep M, Singendonk MMJ, Dall'Oglio L, Gottrand F, Krishnan U, Terheggen-Lagro SWJ, Omari TI, Benninga MA, van Wijk MP

Abstract
Oesophageal atresia (EA) is a congenital abnormality of the oesophagus that is caused by incomplete embryonic compartmentalization of the foregut. EA commonly occurs with a tracheo-oesophageal fistula (TEF). Associated birth defects or anomalies, such as VACTERL association, trisomy 18 or 21 and CHARGE syndrome, occur in the majority of patients born with EA. Although several studies have revealed signalling pathways and genes potentially involved in the development of EA, our understanding of the pathophysiology of EA lags behind the improvements in surgical and clinical care of patients born with this anomaly. EA is treated surgically to restore the oesophageal interruption and, if present, ligate and divide the TEF. Survival is now ~90% in those born with EA with severe associated anomalies and even higher in those born with EA alone. Despite these achievements, long-term gastrointestinal and respiratory complications and comorbidities in patients born with EA are common and lead to decreased quality of life. Oesophageal motility disorders are probably ubiquitous in patients after undergoing EA repair and often underlie these complications and comorbidities. The implementation of several new diagnostic and screening tools in clinical care, including high-resolution impedance manometry, pH-multichannel intraluminal impedance testing and disease-specific quality of life questionnaires now provide better insight into these problems and may contribute to better long-term outcomes in the future.

PMID: 31000707 [PubMed - in process]

Small intestinal bacterial overgrowth in systemic sclerosis: a review of the literature.

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Small intestinal bacterial overgrowth in systemic sclerosis: a review of the literature.

Arch Dermatol Res. 2019 Jan;311(1):1-8

Authors: Polkowska-Pruszyńska B, Gerkowicz A, Szczepanik-Kułak P, Krasowska D

Abstract
Systemic sclerosis (SSc) is a chronic, connective tissue disease with an autoimmune pattern characterized by inflammation, fibrosis and microcirculation changes leading to internal organs malfunctions. Recently, the presence of uncharacteristic gastrointestinal symptoms in the course of SSc has been underlined. The possible cause of such clinical presentation is the small intestinal bacterial overgrowth (SIBO). Nevertheless, these manifestations resulting from gastrointestinal tract hypomotility may occur in numerous disease entities. The systematic review of the literature was performed on MEDLINE database using the relevant MeSH terms including all sub-headings. After further investigation, the initial number of 56 records was limited to 7 results. The study analysis showed an increased presence of SIBO in 39% of patients suffering from SSc. The average SSc duration was longer in SSc patients with coexisting SIBO. SIBO remains a diagnostic and therapeutic challenge and therefore is a significant clinical problem among patients suffering from SSc.

PMID: 30382339 [PubMed - indexed for MEDLINE]

Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and...

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Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

J Pediatr Gastroenterol Nutr. 2018 03;66(3):516-554

Authors: Rosen R, Vandenplas Y, Singendonk M, Cabana M, DiLorenzo C, Gottrand F, Gupta S, Langendam M, Staiano A, Thapar N, Tipnis N, Tabbers M

Abstract
This document serves as an update of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2009 clinical guidelines for the diagnosis and management of gastroesophageal reflux disease (GERD) in infants and children and is intended to be applied in daily practice and as a basis for clinical trials. Eight clinical questions addressing diagnostic, therapeutic and prognostic topics were formulated. A systematic literature search was performed from October 1, 2008 (if the question was addressed by 2009 guidelines) or from inception to June 1, 2015 using Embase, MEDLINE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Clinical Trials. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to define and prioritize outcomes. For therapeutic questions, the quality of evidence was also assessed using GRADE. Grading the quality of evidence for other questions was performed according to the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) and Quality in Prognostic Studies (QUIPS) tools. During a 3-day consensus meeting, all recommendations were discussed and finalized. In cases where no randomized controlled trials (RCT; therapeutic questions) or diagnostic accuracy studies were available to support the recommendations, expert opinion was used. The group members voted on each recommendation, using the nominal voting technique. With this approach, recommendations regarding evaluation and management of infants and children with GERD to standardize and improve quality of care were formulated. Additionally, 2 algorithms were developed, 1 for infants <12 months of age and the other for older infants and children.

PMID: 29470322 [PubMed - indexed for MEDLINE]

A molecular biomarker for prediction of clinical outcome in children with ASD, constipation, and intestinal inflammation.

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A molecular biomarker for prediction of clinical outcome in children with ASD, constipation, and intestinal inflammation.

Sci Rep. 2019 Apr 12;9(1):5987

Authors: Walker SJ, Langefeld CD, Zimmerman K, Schwartz MZ, Krigsman A

Abstract
In children with autism spectrum disorder (ASD) who present to the gastroenterologist with chronic constipation on a background of colonic inflammation, we have identified two distinct clinical subtypes: (1) patients who experience a sustained state of GI symptomatic remission while on maintenance anti-inflammatory therapy (fast responders) and, (2) those with recurrent right-sided fecal loading requiring regular colon cleanouts during treatment for enterocolitis (slow responders). We hypothesized that a detailed molecular analysis of tissue from the affected region of the colon would provide mechanistic insights regarding the fast versus slow response to anti-inflammatory therapy. To test this, ascending colon biopsy tissues from 35 children with ASD (20 slow responders and 15 fast responders) were analyzed by RNAseq. Hierarchical cluster analysis was performed to assign samples to clusters and gene expression analysis was performed to identify differentially expressed transcripts (DETs) between samples within the clusters. Significant differences were found between the two clusters with fast responder-predominant cluster showing an upregulation of transcripts involved in the activation of immune and inflammatory response and the slow responder-predominant cluster showing significant over-representation of pathways impacting colonic motility (e.g. genes involved in tryptophan and serotonin degradation and mitochondrial dysfunction). Regression analysis identified a single long non-coding RNA that could predict cluster assignment with a high specificity (0.88), sensitivity (0.89) and accuracy (0.89). Comparison of gene expression profiles in the ascending colon from a subset of patients with ASD, chronic right-sided fecal loading constipation and a slow versus fast response to therapy has identified molecular mechanisms that likely contribute to this differential response following the primary therapeutic intervention (i.e. treatment for colonic inflammation with brief induction immunosuppression followed by maintenance non-steroidal anti-inflammatory therapy). Importantly, we have identified a transcript that, if validated, may provide a biomarker that can predict from the outset which patients will be slow responders who would benefit from an alternate therapeutic strategy in treating their constipation.

PMID: 30979947 [PubMed - in process]

Pre-operative pediatric cardiac surgery: enema Versus not enema.

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Pre-operative pediatric cardiac surgery: enema Versus not enema.

Acta Biomed. 2019 Mar 28;90(4-S):74-78

Authors: Prendin A, Sansone V, Brugnaro L, De Barbieri I

Abstract
BACKGROUND AND AIM OF THE WORK: There is evidence in adult literature that the enema in the preoperative of thoracic surgery can be dismissed without disadvantage. However, there is a gap of articles about enema in childhood for thoracic surgeries. The aim of the work is  to investigate whether the administration of enema in the preparation for cardiac surgery, the use of different analgosedation drugs and the Extracorporeal Circulation influence the children's intestinal motility in the post-operative period.
METHODS: A retrospective study was carried out comparing the data between users subjected to saline solution enema, originating from the U.O.C. of Pediatric Cardiology and Pediatric Cardiac Surgery and Congenital Heart Disease and users not subjected to such procedure, coming from the U.O.S.D. Pediatric Intensive Care. The data collected will evaluate the intestinal motility in the post-operative cardiac surgery.
RESULTS: The following three variables were analyzed: interval of post-operative evacuation days (mean 2.14, median 2.00, standard deviation 1.525 in non-enema children; mean 2.76, median 2.00, standard deviation 1.318 in enema children), administered analgosedation drugs and use of Extracorporeal Circulation - for which the Pearson Test was used. A sampling bias is also reported from the analysis of the data. The study did not show a statistical significance correlates the variables analyzed to intestinal motility in post-operative period.
CONCLUSION: The sampling bias emerged could reflect the diversity of the catchment area in the two Wards. The study - in agreement with the literature concerning the adult user - proves that the practice of enema evacuation pre-operative cardiac surgery in the pediatric user is unnecessary and does not influence intestinal transit in the post-operative period.

PMID: 30977751 [PubMed - in process]

Novel Pressure-Impedance Parameters for Evaluating Esophageal Function in Pediatric Achalasia.

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Novel Pressure-Impedance Parameters for Evaluating Esophageal Function in Pediatric Achalasia.

J Pediatr Gastroenterol Nutr. 2018 01;66(1):37-42

Authors: Singendonk MMJ, Omari TI, Rommel N, van Wijk MP, Benninga MA, Rosen R, Nurko S

Abstract
OBJECTIVE: In achalasia, absent peristalsis and reduced esophagogastric junction (EGJ) relaxation and compliance underlie dysphagia symptoms. Novel high-resolution impedance manometry variables, that is, bolus presence time (BPT) and trans-EGJ-bolus flow time (BFT) have been developed to estimate the duration of EGJ opening and trans-EGJ bolus flow. The aim of this study was to evaluate esophageal motor function and bolus flow in children diagnosed with achalasia using these variables.
METHODS: High-resolution impedance manometry recordings from 20 children who fulfilled the Chicago Classification (V3) criteria for achalasia were compared with recordings of 15 children with normal esophageal high-resolution manometry findings and no other evidence suggestive of achalasia. Matlab-based analysis software was used to calculate BPT and BFT.
RESULTS: Both BPT and BFT were significantly reduced in achalasia patients compared with children with normal esophageal motility (BPT 3.3 s vs 5.1 s P < 0.01; BFT 1.4 s vs 4.3 s P < 0.001). BFT was significantly lower than BPT (achalasia difference 1.9 s ± 1.3 s, P = 0.001 and normal difference 0.9 ± 0.3 s, P = 0.001). Overall, there was a significant correlation between BPT and BFT (r = 0.825, P < 0.001). We observed a 2-way differentiation of achalasia patients; those in whom the BPT and BFT were proportional, but significantly lower than in patients with normal peristalsis, and those in whom BFT was disproportionately lower than BPT.
CONCLUSIONS: Calculation of BPT and BFT may help determine whether esophageal bolus transport to the EGJ and/or esophageal emptying through the EGJ are aberrant. For achalasia, this may detect flow resistance at the EGJ, potentially improving both diagnosis and objective assessment of therapeutic effects.

PMID: 28604515 [PubMed - indexed for MEDLINE]

Nausea exacerbates symptom burden, quality of life, and functioning in adolescents with functional abdominal pain disorders.

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Nausea exacerbates symptom burden, quality of life, and functioning in adolescents with functional abdominal pain disorders.

Neurogastroenterol Motil. 2019 Apr 07;:e13595

Authors: Kovacic K, Kapavarapu PK, Sood MR, Li BUK, Nugent M, Simpson P, Miranda A

Abstract
BACKGROUND: Nausea frequently co-exists with functional abdominal pain disorders (FAPDs) and may be linked to a higher disease burden. This study aimed to prospectively compare multisystem symptoms, quality of life, and functioning in FAPDs with and without nausea.
METHODS: Adolescents ages 11-18 years fulfilling Rome III criteria for a FAPD were grouped by the presence or absence of chronic nausea. Subjects completed validated instruments assessing nausea (Nausea Profile Questionnaire = NPQ), quality of life (Patient-Reported Outcome Measurement Information System), functioning (Functional Disability Inventory), and anxiety (State-Trait Anxiety Inventory for Children). Group comparisons were performed for instruments, multisystem symptoms, school absences, and clinical diagnoses.
KEY RESULTS: A total of 112 subjects were included; 71% reported chronic nausea. Patients with Nausea compared to No Nausea had higher NPQ scores (P ≤ 0.001), worse quality of life (P = 0.004), and greater disability (P = 0.02). State and trait anxiety scores were similar (P = 0.57, P = 0.25). A higher NPQ score correlated with poorer quality of life, more disability, and higher anxiety. Specific comorbidities were more common in Nausea vs No Nausea group: dizziness (81% vs 41%; P ≤ 0.001), concentrating difficulties (68% vs 27%; P ≤ 0.001), chronic fatigue (58% vs 20%; P = 0.01), and sleep disturbances (73% vs 48%; P = 0.02). The Nausea group reported more school absences (P = 0.001) and more commonly met criteria for functional dyspepsia (P = 0.034).
CONCLUSION AND INFERENCES: Nausea co-existing with FAPDs is associated with a higher extra-intestinal symptom burden, worse quality of life, and impaired functioning in children. Assessing and targeting nausea therapeutically is essential to improve outcomes in FAPDs.

PMID: 30957319 [PubMed - as supplied by publisher]

MicroRNA-155 Modulates Acute Graft-versus-Host Disease by Impacting T Cell Expansion, Migration, and Effector Function.

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MicroRNA-155 Modulates Acute Graft-versus-Host Disease by Impacting T Cell Expansion, Migration, and Effector Function.

J Immunol. 2018 06 15;200(12):4170-4179

Authors: Zitzer NC, Snyder K, Meng X, Taylor PA, Efebera YA, Devine SM, Blazar BR, Garzon R, Ranganathan P

Abstract
MicroRNA-155 (miR-155) is a small noncoding RNA critical for the regulation of inflammation as well as innate and adaptive immune responses. MiR-155 has been shown to be dysregulated in both donor and recipient immune cells during acute graft-versus-host disease (aGVHD). We previously reported that miR-155 is upregulated in donor T cells of mice and humans with aGVHD and that mice receiving miR-155-deficient (miR155-/-) splenocytes had markedly reduced aGVHD. However, molecular mechanisms by which miR-155 modulates T cell function in aGVHD have not been fully investigated. We identify that miR-155 expression in both donor CD8+ T cells and conventional CD4+ CD25- T cells is pivotal for aGVHD pathogenesis. Using murine aGVHD transplant experiments, we show that miR-155 strongly impacts alloreactive T cell expansion through multiple distinct mechanisms, modulating proliferation in CD8+ donor T cells and promoting exhaustion in donor CD4+ T cells in both the spleen and colon. Additionally, miR-155 drives a proinflammatory Th1 phenotype in donor T cells in these two sites, and miR-155-/- donor T cells are polarized toward an IL-4-producing Th2 phenotype. We further demonstrate that miR-155 expression in donor T cells regulates CCR5 and CXCR4 chemokine-dependent migration. Notably, we show that miR-155 expression is crucial for donor T cell infiltration into multiple target organs. These findings provide further understanding of the role of miR-155 in modulating aGVHD through T cell expansion, effector cytokine production, and migration.

PMID: 29720426 [PubMed - indexed for MEDLINE]

Interactions Between Commensal Bacteria and Enteric Neurons, via FPR1 Induction of ROS, Increase Gastrointestinal Motility in Mice.

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Interactions Between Commensal Bacteria and Enteric Neurons, via FPR1 Induction of ROS, Increase Gastrointestinal Motility in Mice.

Gastroenterology. 2019 Mar 28;:

Authors: Chandrasekharan B, Saeedi BJ, Alam A, Houser M, Srinivasan S, Tansey M, Jones R, Nusrat A, Neish AS

Abstract
BACKGROUND & AIMS: Reduced gastrointestinal (GI) motility is a feature of disorders associated with intestinal dysbiosis and loss of beneficial microbes. It is not clear how consumption of beneficial commensal microbes, marketed as probiotics, affects the enteric nervous system (ENS). We studied the effects of the widely used probiotic and the commensal Lactobacillus rhamnosus GG (LGG) on ENS and GI motility in mice.
METHODS: Conventional and germ-free C57B6 mice were gavaged with LGG and intestinal tissues were collected; changes in the enteric neuronal subtypes were assessed by real-time PCR, immunoblots and immunostaining. Production of reactive oxygen species (ROS) in the jejunal myenteric plexi and phosphorylation (p) of mitogen-activated protein kinase 1 (MAPK1) in the enteric ganglia were assessed by immunoblots and immunostaining. Fluorescence in situ hybridization was performed on jejunal cryosections with probes to detect formyl peptide receptor 1 (FPR1). GI motility in conventional mice was assessed after daily gavage of LGG for 1 week.
RESULTS: Feeding of LGG to mice stimulated myenteric production of ROS, increased levels of phosphorylated MAPK1, and increased expression of choline acetyl transferase by neurons (P<.001). These effects were not observed in mice given N-acetyl cysteine (a ROS inhibitor) or LGGΩSpaC (an adhesion-mutant strain of LGG) or FPR1-knockout mice. Gavage of mice with LGG for 1 week significantly increased stool frequency, reduced total GI transit time, and increased contractions of ileal circular muscle strips in ex vivo experiments (P<.05).
CONCLUSIONS: Using mouse models, we found that LGG-mediated signaling in the ENS requires bacterial adhesion, redox mechanisms, and FPR1. This pathway might be activated to increase GI motility in patients.

PMID: 30930024 [PubMed - as supplied by publisher]

Etiology and functional validation of gastrointestinal motility dysfunction in a zebrafish model of CHARGE syndrome.

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Etiology and functional validation of gastrointestinal motility dysfunction in a zebrafish model of CHARGE syndrome.

FEBS J. 2018 06;285(11):2125-2140

Authors: Cloney K, Steele SL, Stoyek MR, Croll RP, Smith FM, Prykhozhij SV, Brown MM, Midgen C, Blake K, Berman JN

Abstract
CHARGE syndrome is linked to autosomal-dominant mutations in the CHD7 gene and results in a number of physiological and structural abnormalities, including heart defects, hearing and vision loss, and gastrointestinal (GI) problems. Of these challenges, GI problems have a profound impact throughout an individual's life, resulting in increased morbidity and mortality. A homolog of CHD7 has been identified in the zebrafish, the loss of which recapitulates many of the features of the human disease. Using a morpholino chd7 knockdown model complemented by a chd7 null mutant zebrafish line, we examined GI structure, innervation, and motility in larval zebrafish. Loss of chd7 resulted in physically smaller GI tracts with normal epithelial and muscular histology, but decreased and disorganized vagal projections, particularly in the foregut. chd7 morphant larvae had significantly less ability to empty their GI tract of gavaged fluorescent beads, and this condition was only minimally improved by the prokinetic agents, domperidone and erythromycin, in keeping with mixed responses to these agents in patients with CHARGE syndrome. The conserved genetics and transparency of the zebrafish have provided new insights into the consequences of chd7 gene dysfunction on the GI system and cranial nerve patterning. These findings highlight the opportunity of the zebrafish to serve as a preclinical model for studying compounds that may improve GI motility in individuals with CHARGE syndrome.

PMID: 29660852 [PubMed - indexed for MEDLINE]

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