Recent PubMed Articles on Gut Motility

Stem cell therapy in severe pediatric motility disorders.

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Stem cell therapy in severe pediatric motility disorders.

Curr Opin Pharmacol. 2018 Oct 16;43:145-149

Authors: McCann CJ, Borrelli O, Thapar N

Abstract
Pediatric gastrointestinal motility disorders represent a range of severe developmental or acquired conditions that disrupt enteric neuromuscular function. Current medical and surgical therapeutic options are very limited but recent advances have highlighted the possibility of improved or curative stem cell-based treatments. Not only has the ability to harvest, propagate and transplant human-derived enteric neural stem cells (ENSCs) been demonstrated but recent in vivo transplantation studies have confirmed that ENSCs are capable of engraftment within recipient intestine of animal models of enteric neuropathy and effecting functional rescue. Pluripotent stem cell-derived cells and pharmacological modulation of both endogenous and transplanted neural stem cells have further enhanced the exciting prospect of clinical application of such stem cell-based therapies in the near future.

PMID: 30340053 [PubMed - as supplied by publisher]

Gastrointestinal Neuropathies: New Insights and Emerging Therapies.

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Gastrointestinal Neuropathies: New Insights and Emerging Therapies.

Gastroenterol Clin North Am. 2018 Dec;47(4):877-894

Authors: Pesce M, Borrelli O, Saliakellis E, Thapar N

Abstract
The bewildering complexity of the enteric nervous system makes it susceptible to develop a wide array of motility disorders, collectively called enteric neuropathies. These gastrointestinal conditions are among the most challenging to manage, mainly given poor characterization of their etiopathophysiology and outcomes. Not surprisingly, therefore, targeted or curative therapies for enteric neuropathies are lacking and management is largely symptomatic. Nonetheless, recent advances in neurogastroenterology have witnessed improvements in established strategies, such as intestinal transplantation and the emergence of new treatments including novel drugs, electrical pacing, and manipulation of fecal microbiota, as well as stem cell and gene therapy.

PMID: 30337038 [PubMed - in process]

Integration of Biomedical and Psychosocial Treatments in Pediatrics Functional Gastrointestinal Disorders.

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Integration of Biomedical and Psychosocial Treatments in Pediatrics Functional Gastrointestinal Disorders.

Gastroenterol Clin North Am. 2018 Dec;47(4):863-875

Authors: van Tilburg MAL, Carter CA

Abstract
Pediatric functional gastrointestinal disorders (FGIDs) are disorders of the brain-gut axis. Pathophysiological factors include alterations in gut motility, microbiota, immune system, central nervous system, and psychosocial factors. Given the complex pathophysiology of FGIDs, many patients are in need of integrative treatment approaches that may include a combination of biomedical, nutritional, and psychological approaches. In this article, we examine goals of treatment; give a brief overview of biomedical, nutritional, and psychological approaches; and finally discuss the integrative management of pediatric FGIDs.

PMID: 30337037 [PubMed - in process]

Gastrointestinal Development: Implications for Management of Preterm and Term Infants.

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Gastrointestinal Development: Implications for Management of Preterm and Term Infants.

Gastroenterol Clin North Am. 2018 Dec;47(4):773-791

Authors: Lenfestey MW, Neu J

Abstract
The gastrointestinal (GI) system provides digestive, absorptive, neuroendocrine, and immunologic functions to support overall health. If normal development is interrupted, a variety of complications and disease can arise. This article explores normal development of the GI tract and specific clinical challenges pertinent to preterm and term infants. Specific topics include abnormal motility, gastroesophageal reflux, current feeding recommendations for preterm infants, effects of parenteral nutrition, and the relationship between the GI tract and the immune system.

PMID: 30337032 [PubMed - in process]

Consensus and contentious statements on the use of probiotics in clinical practice: A south east Asian gastro-neuro motility association working team report.

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Consensus and contentious statements on the use of probiotics in clinical practice: A south east Asian gastro-neuro motility association working team report.

J Gastroenterol Hepatol. 2018 Oct;33(10):1707-1716

Authors: Gwee KA, Lee WW, Ling KL, Ooi CJ, Quak SH, Dan YY, Siah KT, Huang JG, Chua ASB, Hilmi IN, Raja Ali RA, Ong C, Simadibrata M, Abdullah M, Sollano JD, Leelakusolvong S, Gonlachanvit S, Lee YY, Ricaforte-Campos JD, Yin YK, Chong KM, Wong CY

Abstract
The concept of consuming microorganisms in the treatment of a medical condition and in health maintenance has gained much attraction, giving rise to an abundance of medical claims and of health supplements. This study identified relevant clinical questions on the therapeutic use of probiotics and reviewed the literature in irritable bowel syndrome, inflammatory bowel disease, impaired intestinal immunity, liver disease, intestinal infections, and common childhood digestive disorders. Statements were developed to address these clinical questions. A panel of experienced clinicians was tasked to critically evaluate and debate the available data. Both consensus and contentious statements are presented to provide to clinicians a perspective on the potential of probiotics and importantly their limitations.

PMID: 29697855 [PubMed - indexed for MEDLINE]

p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse.

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p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse.

Proc Natl Acad Sci U S A. 2018 Oct 08;:

Authors: Robson MJ, Quinlan MA, Margolis KG, Gajewski-Kurdziel PA, Veenstra-VanderWeele J, Gershon MD, Watterson DM, Blakely RD

Abstract
Autism spectrum disorder (ASD) is a common neurobehavioral disorder with limited treatment options. Activation of p38 MAPK signaling networks has been identified in ASD, and p38 MAPK signaling elevates serotonin (5-HT) transporter (SERT) activity, effects mimicked by multiple, hyperfunctional SERT coding variants identified in ASD subjects. Mice expressing the most common of these variants (SERT Ala56) exhibit hyperserotonemia, a biomarker observed in ASD subjects, as well as p38 MAPK-dependent SERT hyperphosphorylation, elevated hippocampal 5-HT clearance, hypersensitivity of CNS 5-HT1A and 5-HT2A/2C receptors, and behavioral and gastrointestinal perturbations reminiscent of ASD. As the α-isoform of p38 MAPK drives SERT activation, we tested the hypothesis that CNS-penetrant, α-isoform-specific p38 MAPK inhibitors might normalize SERT Ala56 phenotypes. Strikingly, 1-week treatment of adult SERT Ala56 mice with MW150, a selective p38α MAPK inhibitor, normalized hippocampal 5-HT clearance, CNS 5-HT1A and 5-HT2A/2C receptor sensitivities, social interactions, and colonic motility. Conditional elimination of p38α MAPK in 5-HT neurons of SERT Ala56 mice restored 5-HT1A and 5-HT2A/2C receptor sensitivities as well as social interactions, mirroring effects of MW150. Our findings support ongoing p38α MAPK activity as an important determinant of the physiological and behavioral perturbations of SERT Ala56 mice and, more broadly, supports consideration of p38α MAPK inhibition as a potential treatment for core and comorbid phenotypes present in ASD subjects.

PMID: 30297392 [PubMed - as supplied by publisher]

Intestinal Dysmotility Syndromes following Systemic Infection by Flaviviruses.

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Intestinal Dysmotility Syndromes following Systemic Infection by Flaviviruses.

Cell. 2018 Sep 17;:

Authors: White JP, Xiong S, Malvin NP, Khoury-Hanold W, Heuckeroth RO, Stappenbeck TS, Diamond MS

Abstract
Although chronic gastrointestinal dysmotility syndromes are a common worldwide health problem, underlying causes for these disorders are poorly understood. We show that flavivirus infection of enteric neurons leads to acute neuronal injury and cell death, inflammation, bowel dilation, and slowing of intestinal transit in mice. Flavivirus-primed CD8+ T cells promote these phenotypes, as their absence diminished enteric neuron injury and intestinal transit delays, and their adoptive transfer reestablished dysmotility after flavivirus infection. Remarkably, mice surviving acute flavivirus infection developed chronic gastrointestinal dysmotility that was exacerbated by immunization with an unrelated alphavirus vaccine or exposure to a non-infectious inflammatory stimulus. This model of chronic post-infectious gastrointestinal dysmotility in mice suggests that viral infections with tropism for enteric neurons and the ensuing immune response might contribute to the development of bowel motility disorders in humans. These results suggest an opportunity for unique approaches to diagnosis and therapy of gastrointestinal dysmotility syndromes.

PMID: 30293866 [PubMed - as supplied by publisher]

The evolution of magnetic resonance enterography in the assessment of motility disorders in children.

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The evolution of magnetic resonance enterography in the assessment of motility disorders in children.

Eur J Radiol. 2018 Oct;107:105-110

Authors: Menys A, Saliakellis E, Borrelli O, Thapar N, Taylor SA, Watson T

Abstract
Gastrointestinal symptoms including constipation, diarrhoea, pain and bloating represent some of the most common clinical problems for patients. These symptoms can often be managed with cheap, widely available medication or will spontaneously resolve. However, for many patients, chronic GI symptoms persist and frequently come to dominate their lives. At one end of the spectrum there is Inflammatory Bowel Disease (IBD) with a clearly defined but expensive treatment pathway. Contrasting with this is Irritable Bowel Syndrome (IBS), likely a collection of pathologies, has a poorly standardised pathway with unsatisfactory clinical outcomes. Managing GI symptoms in adult populations is a challenge. The clinical burden of gastrointestinal disease is also prevalent in paediatric populations and perhaps even harder to treat. In this review we explore some of the recent advances in magnetic resonance imaging (MRI) to study the gastrointestinal tract. Complex in both its anatomical structure and its physiology we are likely missing key physiological markers of disease through relying on symptomatic descriptors of gut function. Using MRI we might be able to characterise previously opaque processes, such as non-propulsive contractility, that could lead to changes in how we understand even common symptoms like constipation. This review explores recent advances in the field in adult populations and examines how this safe, objective and increasingly available modality might be applied to paediatric populations.

PMID: 30292253 [PubMed - in process]

Altered gastrointestinal motility in an animal model of Lesch-Nyhan disease.

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Altered gastrointestinal motility in an animal model of Lesch-Nyhan disease.

Auton Neurosci. 2018 03;210:55-64

Authors: Zizzo MG, Frinchi M, Nuzzo D, Jinnah HA, Mudò G, Condorelli DF, Caciagli F, Ciccarelli R, Di Iorio P, Mulè F, Belluardo N, Serio R

Abstract
Mutations in the HGPRT1 gene, which encodes hypoxanthine-guanine phosphoribosyltransferase (HGprt), housekeeping enzyme responsible for recycling purines, lead to Lesch-Nyhan disease (LND). Clinical expression of LND indicates that HGprt deficiency has adverse effects on gastrointestinal motility. Therefore, we aimed to evaluate intestinal motility in HGprt knockout mice (HGprt¯). Spontaneous and neurally evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips of distal colon. HGprt¯ tissues showed a lower in amplitude spontaneous activity and atropine-sensitivity neural contraction compared to control mice. The responses to carbachol and to high KCl were reduced, demonstrating a widespread impairment of contractility. L-NAME was not able in the HGprt¯ tissues to restore the large amplitude contractile activity typical of control. In HGprt¯ colon, a reduced expression of dopaminergic D1 receptor was observed together with the loss of its tonic inhibitory activity present in control-mice. The analysis of inflammatory and oxidative stress in colonic tissue of HGprt¯ mice revealed a significant increase of lipid peroxidation associated with over production of oxygen free radicals. In conclusion, HGprt deficiency in mice is associated with a decrease in colon contractility, not dependent upon reduction of acetylcholine release from the myenteric plexus or hyperactivity of inhibitory signalling. By contrast the increased levels of oxidative stress could partially explain the reduced colon motility in HGprt¯ mice. Colonic dysmotility observed in HGprt¯ mice may mimic the gastrointestinal dysfunctions symptoms of human syndrome, providing a useful animal model to elucidate the pathophysiology of this problem in the LND.

PMID: 29305058 [PubMed - indexed for MEDLINE]

Clinical management of pediatric achalasia.

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Clinical management of pediatric achalasia.

Expert Rev Gastroenterol Hepatol. 2018 Apr;12(4):391-404

Authors: van Lennep M, van Wijk MP, Omari TIM, Benninga MA, Singendonk MMJ

Abstract
INTRODUCTION: Achalasia is a rare esophageal motility disorder. Much of the literature is based on the adult population. In adults, guidance of therapeutic approach by manometric findings has led to improvement in patient outcome. Promising results have been achieved with novel therapies such as PerOral Endoscopic Myotomy (POEM). Areas covered: In this review, we provide an overview of the novel diagnostic and therapeutic tools for achalasia management and in what way they will relate to the future management of pediatric achalasia. We performed a PubMed and EMBASE search of English literature on achalasia using the keywords 'children', 'achalasia', 'pneumatic dilation', 'myotomy' and 'POEM'. Cohort studies < 10 cases and studies describing patients ≥ 20 years were excluded. Data regarding patient characteristics, treatment outcome and adverse events were extracted and presented descriptively, or pooled when possible. Expert commentary: Available data report that pneumatic dilation and laparoscopic Heller's myotomy are effective in children, with certain studies suggesting lower success rates in pneumatic dilation. POEM is increasingly used in the pediatric setting with promising short-term results. Gastro-esophageal reflux disease (GERD) may occur post-achalasia intervention due to disruption of the LES and therefore requires diligent follow-up, especially in children treated with POEM.

PMID: 29439587 [PubMed - indexed for MEDLINE]

Esophageal dysmotility: An intrinsic feature of megacystis, microcolon, hypoperistalsis syndrome (MMIHS).

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Esophageal dysmotility: An intrinsic feature of megacystis, microcolon, hypoperistalsis syndrome (MMIHS).

J Pediatr Surg. 2018 Sep 07;:

Authors: Kocoshis SA, Goldschmidt ML, Nathan JD, El-Chammas KI, Bondoc AJ, Tiao GM, Alonso MH, Ubesie AC, Cole CR, Kaul A

Abstract
OBJECTIVES: Megacystis-microcolon-hypoperistalsis syndrome (MMIHS) also called Berdon's Syndrome, is a smooth muscle myopathy that results in an enlarged bladder, microcolon, and small bowel hypoperistalsis. In our series of six patients with this disorder, all had disordered swallowing. Therefore, we prospectively characterized esophageal structure and function in all.
METHODS: Diagnoses had been established by contrast radiography, small bowel manometry, and urodynamic studies. To investigate the esophagus, we endoscoped and biopsied the esophagus of each patient on multiple occasions. All patients also underwent water soluble contrast esophagography and esophageal manometry.
RESULTS: Upon careful questioning, all patients had swallowing dysfunction, and the majority of their enteral intake was via gastrostomy or gastrojejunostomy. All took some oral alimentation, but eating was slow and none could aliment themselves completely by the oral route, receiving 50% or less of their calories by mouth. Four had megaesophagus whereas the esophagus of the two youngest was of normal caliber. All had eosinophilic esophagitis and/or esophageal Candidiasis from time to time, but successful treatment of these findings failed to improve their symptoms. Manometry revealed normal lower esophageal sphincter (LES) resting tone and normal LES relaxation, but for all, peristalsis was absent in the esophageal body.
CONCLUSIONS: This series expands the spectrum of findings in MMIHS, to include a primary motility disorder of the esophageal body. As patients age, the esophageal caliber appears to increase. Successful treatment of neither esophageal eosinophilia nor Candidiasis is effective in ameliorating the motility disorder. If our findings are confirmed in more patients with MMIHS, this disorder should be renamed, megacystis-microcolon-intestinal-and esophageal hypoperistalsis syndrome.
TYPE OF STUDY: Prognosis study, Level IV (case series).

PMID: 30257810 [PubMed - as supplied by publisher]

Chronic Acalculous Cholecystitis in Children with Biliary Symptoms: Usefulness of Hepato-Cholescintigraphy.

Chronic Acalculous Cholecystitis in Children with Biliary Symptoms: Usefulness of Hepato-Cholescintigraphy.

J Pediatr Gastroenterol Nutr. 2018 Sep 25;:

Authors: Kwatra NS, Nurko S, Stamoulis C, Falone AE, Grant FD, Treves ST

Abstract
OBJECTIVES: Chronic acalculous cholecystitis (CAC) increasingly is being diagnosed as a cause of recurring biliary symptoms in children, but its clinical diagnosis remains challenging. The primary objective was to evaluate the utility of hepato-cholescintigraphy in pediatric patients with suspected CAC. A secondary objective was to describe their clinical follow-up after diagnosis.
METHODS: Medical records of patients (aged 9-20 years) who underwent hepato-cholescintigraphy from February 2008 to January 2012 were reviewed. Patients with gallstones, and with ≤1 year of clinical follow-up, and studies without gallbladder (GB) stimulation were excluded. GB ejection fraction (GBEF) of <35% after sincalide or fatty meal (Lipomul) stimulation were considered abnormal. Diagnosis of CAC was based on histopathology following cholecystectomy. Patients with negative GB pathology, or complete resolution of symptoms without surgery, or alternative diagnoses for persistent symptoms were considered to not have CAC.
RESULTS: Eighty-three patients formed the study group (median age 14.9 years), of which 81.9% were females. Median duration of symptoms and clinical follow-up were 6 months and 2.9 years respectively. Fifty-two patients had at least one study with sincalide and 36 patients had at least one study with Lipomul. Initial cholescintigraphy was 95.0% sensitive and 73.0% specific in diagnosing CAC, with a negative predictive value of 97.9%. Of the 31 patients with abnormal GBEF, 22 underwent cholecystectomy with improvement in pain in 72.7%, while all of the 9 without surgery improved.
CONCLUSIONS: Hepato-cholescintigraphy is useful for excluding CAC, although the clinical implications of an abnormal GBEF need to be further defined.

PMID: 30256266 [PubMed - as supplied by publisher]

Prevention and treatment of secretory diarrhea by the lysophosphatidic acid analog Rx100.

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Prevention and treatment of secretory diarrhea by the lysophosphatidic acid analog Rx100.

Exp Biol Med (Maywood). 2018 Sep 25;:1535370218803349

Authors: Thompson KE, Ray RM, Alli S, Ge W, Boler A, Shannon McCool W, Meena AS, Shukla PK, Rao R, Johnson LR, Miller MA, Tigyi GJ

Abstract
Diarrheal disease is a severe global health problem. It is estimated that secretory diarrhea causes 2.5 million deaths annually among children under the age of five in the developing world. A critical barrier in treating diarrheal disease is lack of easy-to-use effective treatments. While antibiotics may shorten the length and severity of diarrhea, oral rehydration remains the primary approach in managing secretory diarrhea. Existing treatments mostly depend on reconstituting medicines with water that is often contaminated which can be an unresolved problem in the developing world. Standard treatments for secretory diarrhea also include drugs that decrease intestinal motility. This approach is less than ideal because in cases where infection is the cause, this can increase the incidence of bacterial translocation and the potential for sepsis. Our goal is to develop a safe, effective, easy-to-use, and inexpensive treatment to reduce fluid loss in secretory diarrhea. We have developed Rx100, which is a metabolically stable analog of lysophosphatidic acid. We tested the hypothesis that Rx100, similarly to lysophosphatidic acid, inhibits the activation of the cystic fibrosis transmembrane regulator Cl- channel and also reduces barrier permeability resulting in the decrease of fluid loss in multiple etiologies of secretory diarrhea. Here we have established the bioavailability and efficacy of Rx100 in cholera toxin-induced secretory diarrhea models. We have demonstrated the feasibility of Rx100 as an effective treatment for Citrobacter rodentium infection-induced secretory diarrhea. Using both the open- and closed-loop mouse models, we have optimized the dosing regimen and time line of delivery for Rx100 via oral and parenteral delivery. Impact statement A critical barrier in treating diarrheal disease is easy-to-use effective treatments. Rx100 is a first in class, novel small molecule that has shown efficacy after both subcutaneous and oral administration in a mouse cholera-toxin- and Citrobacter rodentium infection-induced diarrhea models. Our findings indicate that Rx100 a metabolically stable analog of the lipid mediator lysophosphatidic acid blocks activation of CFTR-mediated secretion responsible for fluid discharge in secretory diarrhea. Rx100 represents a new treatment modality which does not directly block CFTR but attenuates its activation by bacterial toxins. Our results provide proof-of-principle that Rx100 can be developed for use as an effective oral or injectable easy-to-use drug for secretory diarrhea which could significantly improve care by eliminating the need for severely ill patients to regularly consume large quantities of oral rehydration therapies and offering options for pediatric patients.

PMID: 30253666 [PubMed - as supplied by publisher]

Management of esophageal motility disorders in children : a review.

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Management of esophageal motility disorders in children : a review.

Acta Gastroenterol Belg. 2018 Apr-Jun;81(2):295-304

Authors: Kotilea K, Mahler T, Bontems P, Devière J, Louis H

Abstract
Diagnostic criteria for esophageal motor disorders have recently been updated with the advent of high-resolution manometry that gives a precise mapping of peristaltic abnormalities and an indirect view of bolus transit problems. Achalasia, the best-defined motor disorder, is now divided in subsets of manometric phenotypes that predict outcome of treatment and guide our therapeutic approach. Pharmacological therapy using smooth muscle relaxants for spastic esophageal disorders remains poorly effective and used only as a bridge to more effective therapies : endoscopic balloon dilation and surgical myotomy are both effective therapies in achalasia, myotomy being considered as the preferred approach in children because it is aimed to be definitive, while dilations usually have to be repeated. Recently, peroral endoscopic myotomy was introduced as an alternative to surgical myotomy for achalasia, and was rapidly adopted in tertiary referral centers. Showing excellent short-term results, this technique might be also proposed for other esophageal spastic disorders. Gastroesophageal reflux disease and eosinophilic esophagitis, two prevalent diseases in children that may be associated with hypotensive and hypertensive peristaltic abnormalities, have to be searched because specific effective therapies exist for these diseases that may cure the motility disorders.

PMID: 30024702 [PubMed - indexed for MEDLINE]

Characterization of the role of global regulator FliA in the pathophysiology of Pseudomonas aeruginosa infection.

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Characterization of the role of global regulator FliA in the pathophysiology of Pseudomonas aeruginosa infection.

Res Microbiol. 2018 Apr;169(3):135-144

Authors: Lo YL, Chen CL, Shen L, Chen YC, Wang YH, Lee CC, Wang LC, Chuang CH, Janapatla RP, Chiu CH, Chang HY

Abstract
FliA is known to be a sigma factor that regulates bacterial flagella gene expression. Accumulating evidence suggests that FliA is involved in bacterial behavior other than motility. To elucidate the contribution of FliA to Pseudomonas aeruginosa pathophysiology, we analyzed the biological properties and gene expression profiles of a ΔfliA mutant. Transcriptome analysis results demonstrated that the expression levels of flagella biogenesis genes decreased dramatically in the mutant; consequently, the ΔfliA mutant failed to synthesize flagella and exhibited reduced motility. The ΔfliA mutant displayed stronger hemolytic and caseinolytic activities, as well as pyocyanin production. The expression of type 6 secretion system-II genes and interbacterial competition activity was decreased in the ΔfliA mutant. Direct evidence of fliA participation in virulence was obtained from analysis of hypervirulent strain B136-33. Adhesion to and cytotoxicity toward mammalian cells and penetration through cell layers were noted; furthermore, the colonization ability of the fliA::Tn5 mutant in the intestines of laboratory mice was compromised. Notably, the fliA-overexpressing strain displayed phenotypes similar to that of the fliA-defective strain, indicating that optimal FliA levels are critical to bacterial physiology. Our findings indicate that FliA plays diverse roles in P. aeruginosa, not only in flagella biosynthesis, but also in pathophysiology.

PMID: 29432810 [PubMed - indexed for MEDLINE]

Mind the gut: probiotics in paediatric neurogastroenterology.

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Mind the gut: probiotics in paediatric neurogastroenterology.

Benef Microbes. 2018 Sep 10;:1-16

Authors: Salvatore S, Pensabene L, Borrelli O, Saps M, Thapar N, Concolino D, Staiano A, Vandenplas Y

Abstract
The gut-brain axis has recently emerged as a key modulator of human health and the intestinal microbiome has a well-recognised pivotal role in this strong connection. The aim of this narrative review is to update and summarise the effect and clinical applicability of probiotics in paediatric neurogastroenterology. The Cochrane Database and PubMed were searched using keywords relating to different subtypes of functional gastrointestinal disorders (FGIDs) and their symptoms, those relating to the CNS and related neurological or behavioural dysfunction as well as 'probiotic' OR 'probiotics'. Included papers were limited to those including children (aged 0-18 years) and using English language. Although significant effects of specific strains have been reported in infants with FGIDs, heterogeneity amongst the studies (different products and concentrations used and FGID subtypes), has limited the ability to draw an overall conclusion on the clinical value of probiotics. According to different meta-analyses of randomised controlled trials, the use of Lactobacillus reuteri (DSM 17938) was associated with a significant decrease in average crying time in infantile colic. There is moderate evidence for this strain and LGG and limited evidence (based on one study each) for the beneficial effect of VSL#3 and a three-strain bifidobacteria mix in abdominal pain FGIDs, particularly in the irritable bowel disease subgroup of children, but not in functional dyspepsia. There is currently no clear evidence of positive effects of oral probiotics in autistic spectrum disorder. Efficacy and safety of other strains or beneficial effects in other conditions still need to be proven, as probiotic properties are strain-specific, and data cannot be extrapolated to other brain-gut or mood diseases or to other probiotics of the same or different species. To transform the use of probiotics from a tempting suggestion to a promising treatment modality in neurogastroenterological disorders more accurate differentiation of the efficacy-proven strains, clarification of dose, duration, and outcome and a careful selection of the target patients are still necessary.

PMID: 30198327 [PubMed - as supplied by publisher]

Stress adaptation upregulates oxytocin within hypothalamo-vagal neurocircuits.

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Stress adaptation upregulates oxytocin within hypothalamo-vagal neurocircuits.

Neuroscience. 2018 Aug 31;:

Authors: Jiang Y, Holly Coleman F, Kopenhaver Doheny K, Alberto Travagli R

Abstract
Stress plays a pivotal role in the development and/or exacerbation of functional gastrointestinal (GI) disorders. The paraventricular nucleus of the hypothalamus (PVN) contains neurons that are part of the hypothalamic-pituitary-adrenal axis as well as preautonomic neurons innervating, among other areas, gastric-projecting preganglionic neurons of the dorsal vagal complex (DVC). The aim of the present study was to test the hypothesis that stress adaptation upregulates oxytocin within PVN-brainstem vagal neurocircuitry. The retrograde tracer cholera toxin B (CTB) was injected into the DVC of rats which, after post-surgical recovery, were pair-housed and exposed to either homo- or heterotypic stress for five consecutive days. Fecal pellets were counted at the end of each stress load. Two hours after the last stressor, the whole brain was excised. Brainstem and hypothalamic nuclei were analyzed immunohistochemically for the presence of both oxytocin (OXT)-immunopositive cells in identified preautonomic PVN neurons as well as OXT fibers in the DVC. Rats exposed to chronic homotypic, but not chronic heterotypic stress, had a significant increase of both number of CTB+ OXT co-localized neurons in the PVN as well as density of OXT positive fibers in the DVC compared to control rats. These data suggest that preautonomic OXT PVN neurons and their projections to the DVC increase following adaptation to stress, and suggest that the possible up-regulation of OXT within PVN-brainstem vagal neurocircuitry may play a role in the adaptation of GI responses to stress.

PMID: 30176320 [PubMed - as supplied by publisher]

Identifying Therapeutic Targets for Sepsis Research: A Characterization Study of the Inflammatory Players in the Cecal Ligation and Puncture Model.

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Identifying Therapeutic Targets for Sepsis Research: A Characterization Study of the Inflammatory Players in the Cecal Ligation and Puncture Model.

Mediators Inflamm. 2018;2018:5130463

Authors: Nullens S, De Man J, Bridts C, Ebo D, Francque S, De Winter B

Abstract
During sepsis, disturbed gastrointestinal motility and increased mucosal permeability can aggravate sepsis due to the increased risk of bacterial translocation. To help identify new therapeutic targets, there is a need for animal models that mimic the immunological changes in the gastrointestinal tract as observed during human sepsis. We therefore characterized in detail the gastrointestinal neuroimmune environment in the cecal ligation and puncture (CLP) model, which is the gold standard animal model of microbial sepsis. Mice were sacrificed at day 2 and day 7, during which gastrointestinal motility was assessed and cytokines were measured in the serum and the colon. In the spleen, lymph nodes, ileum, and colon, subsets of leukocyte populations were identified by flow cytometry. Septic animals displayed an impaired gastrointestinal motility at day 2 and day 7. Two days post-CLP, increased serum and colonic levels of proinflammatory cytokines were measured. Flow cytometry revealed an influx of neutrophils in the colon and ileum, increased numbers of macrophages in the spleen and mesenteric lymph nodes, and an enhanced number of mast cells in all tissues. At day 7 post-CLP, lymphocyte depletion was observed in all tissues coinciding with increased IL-10 and TGF-β levels, as well as increased colonic levels of IL-17A and IFN-γ. Thus, CLP-induced sepsis in mice results in simultaneous activation of pro- and anti-inflammatory players at day 2 and day 7 in different tissues, mimicking human sepsis.

PMID: 30174555 [PubMed - in process]

The Gut Microbiome in Adult and Pediatric Functional Gastrointestinal Disorders.

The Gut Microbiome in Adult and Pediatric Functional Gastrointestinal Disorders.

Clin Gastroenterol Hepatol. 2018 Aug 25;:

Authors: Shin A, Preidis GA, Shulman R, Kashyap P

Abstract
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 towards therapeutic strategies which rely on better understanding the mediators of gut microbiota-host crosstalk. It is not surprising the gut microbiome has been implicated in pathogenesis of functional gastrointestinal disorders (FGIDs) 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 FGIDs. We summarize the factors which help shape the gut microbiome in humans. 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 towards precise mechanism based microbiota therapies.

PMID: 30153517 [PubMed - as supplied by publisher]

Neonatal factors predictive for respiratory and gastro-intestinal morbidity after esophageal atresia repair.

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Neonatal factors predictive for respiratory and gastro-intestinal morbidity after esophageal atresia repair.

Pediatr Neonatol. 2018 Jul 21;:

Authors: Rayyan M, Embrechts M, Van Veer H, Aerts R, Hoffman I, Proesmans M, Allegaert K, Naulaers G, Rommel N

Abstract
BACKGROUND: Esophageal atresia is a major congenital foregut anomaly. Affected patients often suffer from respiratory and gastro-intestinal morbidity. The objective of this study is to identify possible neonatal predictive factors contributing to a long-term complicated clinical course in patients after repair of esophageal atresia.
METHODS: A total of 93 patients born between 1993 and 2013, with esophageal atresia and surviving the neonatal period were included in this retrospective study. A complicated clinical course was defined as the occurrence of ≥1 of these complications: severe gastro-esophageal reflux, esophageal stricture requiring dilatations, need for tube feeding for >100 days, severe tracheomalacia, severe chronic respiratory disease and death. We used linear models with a binomial distribution to determine risk factors for gastro-intestinal or respiratory complicated evolution and a backward stepwise elimination procedure to reduce models until only significant variables remained in the model. Multinomial logistic regression was used to assess risk factors for different evolutions of complication. Model parameter estimates were used to calculate odds ratios for significant risk factors.
RESULTS: Fifty-seven patients (61%) had a complicated clinical course in the first year of life and 47 (51%) had a complicated evolution during years 1-6. In the first year, prematurity was a significant factor for complicated gastro-intestinal (OR 2.84) and respiratory evolution (OR 2.93). After 1 year, gastro-intestinal morbidity in childhood was associated with VACTERL association (OR 12.2) and a complicated first year (OR 36.1). Respiratory morbidity was associated with congenital heart disease (OR 12.9) and a complicated first year (OR 86.9). Multinomial logistic regression showed that prematurity (p = 0.018) and VACTERL association (p = 0.003) were significant factors of complications.
CONCLUSION: Prematurity is an important predictive factor for a complicated clinical course in early life. A complicated first year often predicts a complicated clinical course in childhood. These risk factors may be helpful in counseling of parents in the neonatal period.

PMID: 30146459 [PubMed - as supplied by publisher]

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