Neurogastroenterology & Motility

Cover image for Vol. 29 Issue 5

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Jim Galligan, Arjan Bredenoord and Stephen Vanner, Associate Editor(s): Maura Corsetti and Kirsteen Browning, Podcast Editor: Adam Farmer

Impact Factor: 3.31

ISI Journal Citation Reports © Ranking: 2015: 26/79 (Gastroenterology & Hepatology); 57/193 (Clinical Neurology); 92/256 (Neurosciences)

Online ISSN: 1365-2982


  1. 1 - 63

    1. New insights into neurogenic cyclic motor activity in the isolated guinea-pig colon

      M. Costa, L. Wiklendt, L. Keightley, S. J. H. Brookes, P. G. Dinning and N. J. Spencer

      Version of Record online: 26 APR 2017 | DOI: 10.1111/nmo.13092

      Thumbnail image of graphical abstract

      This work characterizes cyclic motor complexes (CMCs) generated by maintained distension, applied to long segments of isolated guinea-pig colon. Our findings indicate that CMCs are neurally dependent and do not require changes in muscle tension or contractility to entrain the neural activity underlying their propagation. The CMCs are likely to play an important role interacting with the neuromechanical processes that time the propulsion of multiple natural pellets and may be particularly relevant in conditions of impaction or obstruction, where long segments of colon are simultaneously distended.

    2. Role of wireless motility capsule in the assessment and management of gastrointestinal dysmotility in patients with diabetes mellitus

      C. Rouphael, Z. Arora, P. N. Thota, R. Lopez, J. Santisi, C. Funk and M. Cline

      Version of Record online: 26 APR 2017 | DOI: 10.1111/nmo.13087

      Thumbnail image of graphical abstract

      Wireless Motility Capsule allows the evaluation of the gastrointestinal tract of diabetic patients in a single test. Glycemic control and diabetic microvascular complications are not associated with extent of dysmotility. Wireless motility capsule testing can affect clinical decisions in patients with diabetes mellitus.

    3. Neonatal immune challenge followed by adult immune challenge induces epigenetic-susceptibility to aggravated visceral hypersensitivity

      J. E. Aguirre, J. H. Winston and S. K. Sarna

      Version of Record online: 25 APR 2017 | DOI: 10.1111/nmo.13081

      Thumbnail image of graphical abstract

      Abdominal pain is one of the major symptoms of inflammatory Bowel Disease (IBD). We investigated the hypothesis that neonatal colon immune challenge followed by an adult colon immune challenge upregulates spinal cord BDNF that aggravates visceral sensitivity over and above that induced by adult colon immune challenge alone. We found increased tyrosine hydroxylase expression in the locus ceruleus increases spinal cord norepinephrine that acts on adrenergic receptors to enhance pCREB binding to the cAMP response element, which recruits histone acetyltransferases (HAT) to the BDNF gene to enhance its transcription resulting in aggravated visceromotor response to colorectal distension, when these rats are subjected to an adult colon immune challenge.

    4. Assessment of motion of colonic contents in the human colon using MRI tagging

      S. E. Pritchard, J. Paul, G. Major, L. Marciani, P. A. Gowland, R. C. Spiller and C. L. Hoad

      Version of Record online: 25 APR 2017 | DOI: 10.1111/nmo.13091

      Thumbnail image of graphical abstract

      This article reports the first successful use of an MRI tagging technique to show differences in the movement of chyme in the ascending colon of subjects with constipation and healthy controls following a 500 mL macrogol stimulus. These differences were assessed using a novel analysis technique.

    5. Abdominal vagus nerve stimulation as a new therapeutic approach to prevent postoperative ileus

      N. Stakenborg, A. M. Wolthuis, P. J. Gomez-Pinilla, G. Farro, M. Di Giovangiulio, G. Bosmans, E. Labeeuw, M. Verhaegen, I. Depoortere, A. D'Hoore, G. Matteoli and G. E. Boeckxstaens

      Version of Record online: 21 APR 2017 | DOI: 10.1111/nmo.13075

      Thumbnail image of graphical abstract

      Vagus nerve stimulation (VNS) has anti-inflammatory effects in immune-mediated disorders such as sepsis and postoperative ileus. Traditionally, VNS has always been performed at cervical level. In this article, we evaluated the anti-inflammatory properties of abdominal VNS in sepsis and postoperative ileus, thus avoiding additional incisions in the neck.

    6. Neurogenic and myogenic patterns of electrical activity in isolated intact mouse colon

      T. J. Hibberd, M. Costa, L. Travis, S. J. H. Brookes, D. A. Wattchow, J. Feng, H. Hu and N. J. Spencer

      Version of Record online: 18 APR 2017 | DOI: 10.1111/nmo.13089

      Thumbnail image of graphical abstract

      Patterns of electrical activity in smooth muscle of whole mouse colon were studied. Distinct neurogenic spike burst and myogenic spike burst patterns were revealed. Neurogenic spike bursts were highly sensitive to electrical and mechanical stimuli and likely correlate with CMMCs while myogenic spike bursts lacked sensitivity to mechanical and electrical stimuli and may correspond to slow myogenic contractions.

    7. Colonic gas homeostasis: Mechanisms of adaptation following HOST-G904 galactooligosaccharide use in humans

      M. Mego, A. Accarino, G. Tzortzis, J. Vulevic, G. Gibson, F. Guarner and F. Azpiroz

      Version of Record online: 18 APR 2017 | DOI: 10.1111/nmo.13080

      Thumbnail image of graphical abstract

      Effect of HOST-G904 administration on the volume of gas evacuated. Anal evacuation of endogenous gas (produced by bacterial fermentation) 2-4 hours after a probe meal with and without gaseous wash-out measured before, at the beginning and after 2 week administration (n=10). With gaseous wash-out, most endogenous gas produced by colonic fermentation was flushed out and evacuated per anus: gas production increased in the early administration phase and returned back to baseline. Without wash-out, a large proportion of the gas produced by bacterial fermentation was eliminated from the lumen before reaching the anus and the proportion tended to increase during HOST-G904 administration.

    8. Traumatic stress-induced persistent changes in DNA methylation regulate neuropeptide Y expression in rat jejunum

      S. Sagarkar, S. Mahajan, A. G. Choudhary, C. D. Borkar, D. M. Kokare and A. J. Sakharkar

      Version of Record online: 18 APR 2017 | DOI: 10.1111/nmo.13074

      Thumbnail image of graphical abstract

      This study investigates the role of DNA methylation in long-lasting changes in trauma-induced neuropeptide Y (NPY) expression in the jejunum and gut motility. The persistent alterations in DNA methylation at the NPY gene promoter due to minimal traumatic brain injury (MTBI) plausibly increased NPY levels resulting into weakened gut motility. Therefore, the novel results of this study implicate DNA methylation as an epigenetic mechanism involved in the regulation of NPY expression in the gut and further suggest it as a therapeutic target for the trauma-induced gut functions.

    9. The effects and mechanism of action of methane on ileal motor function

      Y. M. Park, Y. J. Lee, Z. Hussain, Y. H. Lee and H. Park

      Version of Record online: 18 APR 2017 | DOI: 10.1111/nmo.13077

      Thumbnail image of graphical abstract

      The actions of methane on the intestine are affected by the cholinergic pathway of the enteric nervous system, supporting the classification of methane as a gasotransmitter.

    10. What is the clinical significance of esophagogastric junction outflow obstruction? evaluation of 60 patients at a tertiary referral center

      F. C. Okeke, S. Raja, K. L. Lynch, S. Dhalla, M. Nandwani, E. M. Stein, B. Chander Roland, M. A. Khashab, P. Saxena, V. Kumbhari, N. K. Ahuja and J. O. Clarke

      Version of Record online: 9 APR 2017 | DOI: 10.1111/nmo.13061

    11. The NO/cGMP pathway in duodenal motor, mechano- and chemosensory responses to acid: A randomized, placebo-controlled study with sildenafil in healthy volunteers

      K. J. Lee, H. Vanheel, T. Vanuytsel, R. Vos and J. Tack

      Version of Record online: 6 APR 2017 | DOI: 10.1111/nmo.13076

      Thumbnail image of graphical abstract

      Sildenafil does not affect duodenal motor, mechanosensory, and chemosensory responses to acid in healthy controls. Therefore, it is less likely that the NO pathway plays a role in the altered response to acid in functional dyspepsia patients.

    12. Novel 3D high-resolution manometry metrics for quantifying esophagogastric junction contractility

      Zhiyue Lin, Yinglian Xiao, Yuwen Li, John E. Pandolfino, Minhu Chen and Peter J. Kahrilas

      Version of Record online: 5 APR 2017 | DOI: 10.1111/nmo.13054

      Thumbnail image of graphical abstract

      We devised novel 3D-HRM metrics to quantify the CD (3D-DHA) and LES (3D-LESP) elements of EGJ contractility. Both measures correlated strongly with conventional HRM metrics of EGJ contractility. The 3D-DHA, in particular, correlated strongly with the EGJ-CI suggesting that both are largely determined by CD contractility. It is hoped that future studies will show these new metrics useful in quantifying elements of the antireflux barrier in mechanistically defined subsets of GERD patients.

    13. Tryptase potentiates enteric nerve activation by histamine and serotonin: Relevance for the effects of mucosal biopsy supernatants from irritable bowel syndrome patients

      D. Ostertag, A. Annahazi, D. Krueger, K. Michel, I. E. Demir, G. O. Ceyhan, F. Zeller and M. Schemann

      Version of Record online: 4 APR 2017 | DOI: 10.1111/nmo.13070

      Thumbnail image of graphical abstract

      Biopsy supernatants of irritable bowel syndrome patients activate enteric neurons despite the low concentrations of tryptase, histamine, and serotonin which individually would not cause spike discharge. We found that tryptase synergistically potentiated the response to individual and combined application of histamine and serotonin. This potentiation was mediated by proteolytic activity of tryptase rather than protease activated receptor 2 activation. Our findings identified synergism between neuroactive substances as a plausible explanation for their pronounced effects as a cocktail.

    14. Appetite influences the responses to meal ingestion

      T. Pribic, A. Nieto, L. Hernandez, C. Malagelada, A. Accarino and F. Azpiroz

      Version of Record online: 31 MAR 2017 | DOI: 10.1111/nmo.13072

      Thumbnail image of graphical abstract

      Effect of appetite on the responses to a meal. As compared to a low-calorie breakfast, a high-calorie breakfast reduced basal hunger sensation, and selectively influenced the responses to a meal ingested 2 hour later: it increased satiety and fullness, but reduced the expected postprandial experience of digestive well-being.


    1. Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group

      S. Roman, C. P. Gyawali, E. Savarino, R. Yadlapati, F. Zerbib, J. Wu, M. Vela, R. Tutuian, R. Tatum, D. Sifrim, J. Keller, M. Fox, J. E. Pandolfino, A. J. Bredenoord and the GERD consensus group

      Version of Record online: 31 MAR 2017 | DOI: 10.1111/nmo.13067

      Thumbnail image of graphical abstract

      The consensus group proposes to define pathological GERD as at least one of the following criteria: Grade C or D esophagitis, peptic stricture, Barrett's mucosa >1 cm and esophageal acid exposure >6%. Number of reflux episodes and baseline impedance should be considered as exploratory tools for further research.


    1. L. fermentum CECT 5716 prevents stress-induced intestinal barrier dysfunction in newborn rats

      T. Vanhaecke, P. Aubert, P.-A. Grohard, T. Durand, P. Hulin, P. Paul-Gilloteaux, A. Fournier, F. Docagne, A. Ligneul, C. Fressange-Mazda, P. Naveilhan, H. Boudin, P. Le Ruyet and M. Neunlist

      Version of Record online: 31 MAR 2017 | DOI: 10.1111/nmo.13069

      Thumbnail image of graphical abstract

      CECT5716 (L. fermentum) strain prevented stress-induced changes in permeability in vivo and reduced small intestinal but not colonic permeability. In addition, L. fermentum reduced stress-induced changes in tight junction organization. L. fermentum enhanced exploratory behavior and increased IFNγ production in splenocytes.

    2. Esophageal sensitivity to acid in patients with Barrett's esophagus is not related to preserved esophageal mucosal integrity

      P. W. Weijenborg, A. J. P. M. Smout, K. K. Krishnadath, J. G. H. M. Bergman, J. Verheij and A. J. Bredenoord

      Version of Record online: 30 MAR 2017 | DOI: 10.1111/nmo.13066

      Thumbnail image of graphical abstract

      Patients with a Barrett's esophagus usually have severe gastroesophageal reflux, however, often experience few reflux symptoms. We concluded that esophageal sensitivity to acid is less pronounced in patients with a Barrett's esophagus than in GERD patients without Barrett. Nevertheless, esophageal mucosal barrier function is equally impaired in those groups and does not seem to explain the difference in acid sensitivity.

    3. Disrupted intrinsic connectivity of the periaqueductal gray in patients with functional dyspepsia: A resting-state fMRI study

      P. Liu, G. Wang, Y. Liu, F. Zeng, D. Lin, X. Yang, F. Liang, V. D. Calhoun and W. Qin

      Version of Record online: 24 MAR 2017 | DOI: 10.1111/nmo.13060

      Thumbnail image of graphical abstract

      This study investigated the periaqueductal gray (PAG) functional connectivity in patients with functional dyspepsia (FD). Patients had disrupted PAG connectivity with the orbitofrontal cortex, prefrontal cortex, insula, and hippocampus/parahippocampus compared to controls. Patients with high level of anxiety and depression had altered PAG connectivity with the prefrontal cortex, anterior cingulate cortex, precuneus, and caudate compared to other patients. These findings indicated that the abnormal PAG intrinsic connectivity might be involved in the development and maintenance of FD.

    4. The selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056) reduces the incidence of reflux episodes in dogs and patients with moderate to severe gastroesophageal reflux disease

      M.-L. Rouzade-Dominguez, N. Pezous, O. J. David, R. Tutuian, S. Bruley des Varannes, J. Tack, P. Malfertheiner, H.-D. Allescher, M. Ufer and A. Rühl

      Version of Record online: 23 MAR 2017 | DOI: 10.1111/nmo.13058

      Thumbnail image of graphical abstract

      Esophageal sphincter tone is partially modulated by metabotropic glutamate receptors. This study assessed the impact of the metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056) on gastro-esophageal reflux in dogs and humans.

    5. 5-HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract

      V. Pauwelyn and R. A. Lefebvre

      Version of Record online: 23 MAR 2017 | DOI: 10.1111/nmo.13064

      Thumbnail image of graphical abstract

      In vitro studies showed that 5-HT4 receptor stimulation enhances myenteric cholinergic neurotransmission in gastrointestinal muscle of several species, but not yet in mice. In smooth muscle strips of murine fundus, jejunum, and colon, the selective 5-HT4 receptor agonist prucalopride enhanced electrically induced submaximal cholinergic contractions; this effect was abolished by selective 5-HT4 receptor antagonism and confirmed with 5-HT, illustrating that 5-HT4 receptor stimulation also enhances murine myenteric cholinergic neurotransmission. This murine in vitro model is useful to further investigate the pharmacology and signal transduction of 5-HT4 receptors increasing the function of myenteric cholinergic neurons.

    6. Severely impaired gastric accommodation is a hallmark of post-Nissen functional dyspepsia symptoms

      A. Pauwels, V. Boecxstaens, C. Broers and J. F. Tack

      Version of Record online: 20 MAR 2017 | DOI: 10.1111/nmo.13063

      Thumbnail image of graphical abstract

      Patients with post-Nissen dyspepsia show a symptom pattern similar to that in FD patients with postprandial distress syndrome, and the main underlying mechanism seems to be impaired gastric accommodation to a meal.

    7. Prospective evaluation of same day versus next day colon manometry results in children with medical refractory constipation

      R. A. Arbizu, S. Nurko, N. Heinz, M. Amicangelo and L. Rodriguez

      Version of Record online: 20 MAR 2017 | DOI: 10.1111/nmo.13050

      Thumbnail image of graphical abstract

      This study in pediatric patients with medical refractory constipation highlights the changes in colon manometry parameters and study interpretation from the day the motility catheter is placed with colonoscopy under anesthesia to the following day.

    8. Esophageal stasis in achalasia patients without symptoms after treatment does not predict symptom recurrence

      F. B. van Hoeij, A. J. P. M. Smout and A. J. Bredenoord

      Version of Record online: 20 MAR 2017 | DOI: 10.1111/nmo.13059

      Thumbnail image of graphical abstract

      After treatment, some achalasia patients have good symptom resolution, despite poor esophageal emptying. After 2 years, these patients had a more dilated esophagus but they did not have a higher chance of symptom recurrence or need for retreatment.

    9. The BDNF polymorphism Val66Met may be predictive of swallowing improvement post pharyngeal electrical stimulation in dysphagic stroke patients

      H. Essa, D. H. Vasant, A. Raginis-Zborowska, A. Payton, E. Michou and S. Hamdy

      Version of Record online: 20 MAR 2017 | DOI: 10.1111/nmo.13062

      Thumbnail image of graphical abstract

      The BDNF polymorphism Val66Met may be predictive of swallowing improvement post pharyngeal electrical stimulation in dysphagic stroke patients.


    1. What's new in Rome IV?

      J. Tack and D. A. Drossman

      Version of Record online: 17 MAR 2017 | DOI: 10.1111/nmo.13053


    1. Computer vision-based diameter maps to study fluoroscopic recordings of small intestinal motility from conscious experimental animals

      I. Ramírez, J. J. Pantrigo, A. S. Montemayor, A. E. López-Pérez, M. I. Martín-Fontelles, S. J. H. Brookes and R. Abalo

      Version of Record online: 16 MAR 2017 | DOI: 10.1111/nmo.13052

      Thumbnail image of graphical abstract

      The automatic method developed here allows for spatiotemporal (Dmaps) and wave frequencies to be obtained, needs little investigator output.

    2. The case of self-resolving type III achalasia after bilateral lung transplant

      P. Aggarwal, V. Bansal, N. Aggarwal, Z. Arora, S. Murthy and S. Gabbard

      Version of Record online: 16 MAR 2017 | DOI: 10.1111/nmo.13048

      Thumbnail image of graphical abstract

      Achalasia is generally considered to be an incurable disease as per the published guidelines. We present here, the first report of a patient with post-surgical achalasia which resolved spontaneously. This case supports the hypothesis that post-surgical or post-traumatic achalasia may represent a different entity.

    3. Psychological stress-induced colonic barrier dysfunction: Role of immune-mediated mechanisms

      P. Hattay, D. K. Prusator, L. Tran and B. Greenwood-Van Meerveld

      Version of Record online: 16 MAR 2017 | DOI: 10.1111/nmo.13043

      Thumbnail image of graphical abstract

      Repetitive daily exposure to water avoidance stress decreased permeability and altered tight junction protein expression within colonic tissue compared to sham controls. In the absence of a histologically defined inflammation, we showed a significant positive correlation between TNF-α and expression of claudin-2.

    4. Assessing the colonic microbiome, hydrogenogenic and hydrogenotrophic genes, transit and breath methane in constipation

      P. G. Wolf, G. Parthasarathy, J. Chen, H. M. O'Connor, N. Chia, A. E. Bharucha and H. Rex Gaskins

      Version of Record online: 13 MAR 2017 | DOI: 10.1111/nmo.13056

      Thumbnail image of graphical abstract

      The relationship between colonic microbiota, transit, and breath hydrogen and methane production in chronic constipation is unclear. Corroborating our earlier findings with 16S rRNA genes, colonic mucosal but not fecal hydrogenogenic and hydrogenotrophic genes were more abundant in constipated than healthy subjects independent of colonic transit. Breath gas excretion after lactulose was not correlated with the abundance of target genes contributing to their production.

    5. Rome III functional dyspepsia symptoms classification: Severity vs frequency

      F. Carbone, L. Holvoet, T. Vanuytsel and J. Tack

      Version of Record online: 13 MAR 2017 | DOI: 10.1111/nmo.13024

      Thumbnail image of graphical abstract

      Frequency (A) ad severity (B) of dyspepsia symptoms in functional dyspepsia subgroups: the epigastric pain syndrome (EPS), the postprandial distress syndrome (PDS) and the overlap group. This study showed that the information given by the assessment of frequency and severity of PDS symptoms is comparable and hence one of the scores sufficiently identifies symptom pattern in PDS patients. In EPS patients, both the symptom frequency and severity should be taken into account as two separate entities.

    6. A double-blind, placebo-controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrhea-predominant IBS

      K. Hod, A. D. Sperber, Y. Ron, M. Boaz, R. Dickman, S. Berliner, Z. Halpern, N. Maharshak and R. Dekel

      Version of Record online: 8 MAR 2017 | DOI: 10.1111/nmo.13037

      Thumbnail image of graphical abstract

      Our randomized clinical trial demonstrates that an 8-week treatment with a probiotic mixture (BIO-25) improved symptoms in women with IBS-D, but was not superior to placebo. We also did not find any significant changes in hs-CRP or calprotectin levels. This rigorously designed and executed study supports the findings of other studies that did not demonstrate superiority of other probiotics over placebo in IBS.

    7. Alterations in the small intestinal wall and motor function after repeated cisplatin in rat

      J. A. Uranga, J. M. García-Martínez, C. García-Jiménez, G. Vera, M. I. Martín-Fontelles and R. Abalo

      Version of Record online: 6 MAR 2017 | DOI: 10.1111/nmo.13047

      Thumbnail image of graphical abstract

      In this study, we have evaluated the effects of the antineoplastic drug cisplatin on the rat small intestinal wall 1 week after a five-cycle treatment. At that time point, small intestinal transit (but not gastric emptying) was delayed, and several histological and immunohistological features of the gut wall and the expression of ICC and different myenteric neuronal populations were altered, supporting the results on motor function.


    1. Rectal gas volume: Defining cut-offs for screening for evacuation disorders in patients with constipation

      S.-Y. Park, D. Khemani, A. Acosta, D. Eckert and M. Camilleri

      Version of Record online: 6 MAR 2017 | DOI: 10.1111/nmo.13044

      Thumbnail image of graphical abstract

      Diagnosis of rectal evacuation disorders (RED) is currently based on anorectal manometry and evacuation tests in specialized laboratories; we recently showed higher rectal gas volume (RGV) and maximum rectal gas transaxial area (MRGTA) measured on abdominal and pelvic computer tomography (CT) in patients with documented RED. Our aim was to obtain cut-off values of RGV, MRGTA, and rectal area on scout film to differentiate constipated patients with RED from those without RED, based on anorectal manometry, balloon expulsion test, and colon transit test. Rectal gas measurements on abdominal imaging may indicate RED in patients with constipation.


    1. Pharyngeal stimulus-induced reflexes are impaired in infants with perinatal asphyxia: Does maturation modify?

      P. S. Jensen, I. K. Gulati, T. R. Shubert, S. Sitaram, M. Sivalingam, K. A. Hasenstab, M. A. El-Mahdy and S. R. Jadcherla

      Version of Record online: 3 MAR 2017 | DOI: 10.1111/nmo.13039

      Thumbnail image of graphical abstract

      We evaluated pharyngo-esophageal protective reflexes following pharyngeal stimulation in hypoxic ischemic encephalopathy (HIE) infants studied longitudinally vs controls. High-resolution manometry analysis showed that these reflexes are impaired in HIE infants which may be responsible for inadequate clearance of secretions, ascending refluxate, and oropharyngeal bolus. Strategies to optimize these reflexes are needed to ensure aerodigestive safety during oral feeding.

    2. Localization of the 5-hydroxytryptamine 4 receptor in equine enteric neurons and extrinsic sensory fibers

      F. Giancola, A. M. Rambaldi, F. Bianco, S. Iusco, N. Romagnoli, C. Tagliavia, C. Bombardi, P. Clavenzani, R. De Giorgio and R. Chiocchetti

      Version of Record online: 3 MAR 2017 | DOI: 10.1111/nmo.13045

      Thumbnail image of graphical abstract

      The 5-hydroxytryptamine 4 receptor (5-HT4) exerts a prominent control on gastrointestinal functions. Morphological data describing its localization in the enteric nervous system of large mammals, including horses, are lacking. In healthy horses, 5-HT4 was identified in some spinal ganglia neurons and large percentages of enteric neurons; in aganglionic foals, 5-HT4 was localized in visceral extrinsic sensory fibers. Our results demonstrate that 5-HT4 is widely expressed by different subsets of enteric neurons and by extrinsic visceral sensory fibers.

    3. Multiple functional gastrointestinal disorders linked to gastroesophageal reflux and somatization: A population-based study

      R. S. Choung, G. Richard Locke III, C. D. Schleck, A. R. Zinsmeister and N. J. Talley

      Version of Record online: 3 MAR 2017 | DOI: 10.1111/nmo.13041

      Thumbnail image of graphical abstract

      This study showed that the coexistence of upper and lower FGIDs as well as gastroesophageal reflux (GER) symptoms is common in the community. Moreover, the higher the somatization score, the more likely the overlap of FGID-GER complexes suggesting a dose–response like effect.

    4. You have free access to this content
      The nutrient-sensing repertoires of mouse enterochromaffin cells differ between duodenum and colon

      A. M. Martin, A. L. Lumsden, R. L. Young, C. F. Jessup, N. J. Spencer and D. J. Keating

      Version of Record online: 2 MAR 2017 | DOI: 10.1111/nmo.13046

      Thumbnail image of graphical abstract

      EC cells are sensory gut endocrine cells that secrete serotonin in response to nutrients. We isolated and purified mouse EC cells from duodenum and colon to compare the expression of genes encoding for numerous nutrient receptors and transporters. We find that the nutrient-sensing capacity of EC cells changes depending on the site these cells are located within the GI tract.

    5. 3D High-definition anorectal manometry: Values obtained in asymptomatic volunteers, fecal incontinence and chronic constipation. Results of a prospective multicenter study (NOMAD)

      F. Mion, A. Garros, C. Brochard, V. Vitton, A. Ropert, M. Bouvier, H. Damon, L. Siproudhis and S. Roman

      Version of Record online: 2 MAR 2017 | DOI: 10.1111/nmo.13049

      Thumbnail image of graphical abstract

      Reference values for 3D high definition anorectal manometry have to be stratified by sex and age. Women with fecal incontinence have significantly lower anal pressure values than asymptomatic women. 3D high definition anorectal manometry push maneuvers do not allow to distinguish between asymptomatic and constipated women.

    6. Sham acupuncture is as efficacious as true acupuncture for the treatment of IBS: A randomized placebo controlled trial

      C. Lowe, A. Aiken, A. G. Day, W. Depew and S. J. Vanner

      Version of Record online: 2 MAR 2017 | DOI: 10.1111/nmo.13040

      Thumbnail image of graphical abstract

      IBS patients were randomized to sham or true acupuncture and symptoms were assessed after a 4 week treatment period and a 12 week follow-up. While a significant improvement in the true acupuncture group was seen at both time points, it did not differ from that of the sham acupuncture group. This suggests that acupuncture does not have an active treatment effect in most IBS patients.

    7. Comparison of motor diagnoses by Chicago Classification versions 2.0 and 3.0 on esophageal high-resolution manometry

      A. Patel, B. Cassell, N. Sainani, D. Wang, B. Shahid, M. Bennett, F. A. Mirza, S. Munigala and C. P. Gyawali

      Version of Record online: 23 FEB 2017 | DOI: 10.1111/nmo.13042

      Thumbnail image of graphical abstract

      Diagnostic criteria for motor diagnoses are different between Chicago Classification (CC) 2.0 and 3.0. We evaluated over 2500 studies using both sets of diagnostic criteria. CC 3.0 is less sensitive in identifying motor diagnoses, but selects out conditions associated with higher symptom burden compared to CC 2.0. Abnormalities in the contraction wave are not well identified by both CC versions, and therefore a ‘normal’ designation on CC remains compatible with contraction wave abnormalities (CWA). We demonstrate that CWA are clinically relevant, are associated with a higher likelihood of esophageal symptoms compared to true normal studies, and may need to be recognized before designating a manometric study as normal.

    8. Pathophysiology of fecal incontinence in obese patients: A prospective case-matched study of 201 patients

      C. Brochard, A. Vénara, A. Bodère, A. Ropert, G. Bouguen and L. Siproudhis

      Version of Record online: 23 FEB 2017 | DOI: 10.1111/nmo.13051

      Thumbnail image of graphical abstract

      Obese patients with fecal incontinence (FI) had a comparable severity of FI and quality of life to those of non-obese patients with FI. Stool consistency is the main factor associated with obesity in FI.

    9. You have full text access to this OnlineOpen article
      Optimal dose of ramosetron in female patients with irritable bowel syndrome with diarrhea: A randomized, placebo-controlled phase II study

      S. Fukudo, K. Matsueda, K. Haruma, M. Ida, H. Hayase, H. Akiho, Y. Nakashima and M. Hongo

      Version of Record online: 16 FEB 2017 | DOI: 10.1111/nmo.13023

      Thumbnail image of graphical abstract

      Effect of 5-HT3 antagonist on irritable bowel syndrome with diarrhea (IBS-D) was believed to be gender-specific. However, is it due to the failure of finding optimal dose which is different between men and women? This randomized, placebo-controlled dose-finding study clearly showed that 2.5 μg of ramosetron which is a half dose for men is the most effective on several key outcomes in women with IBS-D. Difference in optimal dose of 5-HT3 antagonist on IBS-D patients between men and women provides further research concept on the serotonergic regulation of brain-gut interactions in humans.

    10. G protein-coupled estrogen receptor and estrogen receptor ligands regulate colonic motility and visceral pain

      M. Zielińska, J. Fichna, M. Bashashati, S. Habibi, A. Sibaev, J.-P. Timmermans and M. Storr

      Version of Record online: 12 FEB 2017 | DOI: 10.1111/nmo.13025

      Thumbnail image of graphical abstract

      Estrogen receptors (ER) and G protein-coupled estrogen receptors are involved in colonic motility and visceral pain. GPER is expressed in the human colon. G-1, a selective GPER agonist, and estradiol, a non-selective ER agonist, inhibited muscle contractility in vitro in human colon.

    11. The effect of pneumatic dilation in management of postfundoplication dysphagia

      D. Sunjaya, A. Podboy, S. H. Blackmon, D. Katzka and M. Halland

      Version of Record online: 12 FEB 2017 | DOI: 10.1111/nmo.13030

      Thumbnail image of graphical abstract

      Pneumatic dilation is a safe treatment option for PPFD with modest reduction in dysphagia score. Patients who developed PPFD after a hiatal hernia repair may gain the greatest benefit after pneumatic dilation.

    12. Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome

      A. Fikree, Q. Aziz and D. Sifrim

      Version of Record online: 12 FEB 2017 | DOI: 10.1111/nmo.13029

      Thumbnail image of graphical abstract

      No studies have examined the physiological abnormalities associated with esophageal symptoms in patients with JHS, divided by PoTS status. The majority of JHS patients with reflux symptoms have true pathological reflux and those with dysphagia have a high prevalence of mild esophageal hypomotility. These abnormalities are more striking in the subgroup of patents with PoTS.

    13. Small intestinal bacterial overgrowth and celiac disease: A systematic review with pooled-data analysis

      G. Losurdo, A. Marra, E. Shahini, B. Girardi, F. Giorgio, A. Amoruso, A. Pisani, D. Piscitelli, M. Barone, M. Principi, A. Di Leo and E. Ierardi

      Version of Record online: 12 FEB 2017 | DOI: 10.1111/nmo.13028

      Thumbnail image of graphical abstract

      A relationship between celiac disease (CD) and SIBO has been hypothesized. In particular, CD seemed to be a predisposing factor for SIBO. The prevalence of SIBO in CD is high, but the results are influenced by the test used to diagnose SIBO and by the response to gluten-free diet. The high heterogeneity between studies is a limit to clarify the relationship between the two disorders. Nevertheless, our analysis suggests that SIBO could be more common in CD when symptoms do not improve after GFD, thus suggesting its detection and treatment in such cases before diagnosing a refractory CD.

    14. Gene expression profiles in peripheral blood mononuclear cells correlate with salience network activity in chronic visceral pain: A pilot study

      A. Gupta, S. Cole, J. S. Labus, S. Joshi, T. J. Nguyen, L. A. Kilpatrick, K. Tillisch, B. D. Naliboff, L. Chang and E. A. Mayer

      Version of Record online: 12 FEB 2017 | DOI: 10.1111/nmo.13027

      Thumbnail image of graphical abstract

      Results show a difference in correlation between PBMC gene expression levels and salience network connectivity in patients with IBS vs. HCs. Inflammatory genes (IL6 and APOL2) are positively correlated with connectivity within salience network in IBS patients (strengthened connectivity). Genes with anti-inflammatory properties (KRT8, APOA4, KRT8A) and 1 inflammatory gene (APOL2) are negatively correlated with connectivity within salience network in HCs (weakened connectivity.

    15. Learning by experience? Visceral pain-related neural and behavioral responses in a classical conditioning paradigm

      A. Icenhour, F. Labrenz, C. Ritter, N. Theysohn, M. Forsting, U. Bingel and S. Elsenbruch

      Version of Record online: 8 FEB 2017 | DOI: 10.1111/nmo.13026

      Thumbnail image of graphical abstract

      Using fMRI, we addressed neural and behavioral correlates of nocebo responses induced by classical conditioning in a visceral pain model. Prior conditioning induced enhanced activation in sensory, cingulate, and prefrontal regions during anticipation and visceral sensation, whereas perceptual ratings were unaffected by conditioning. In the absence of behavioral effects, neural findings may reflect hypervigilance involving increased attention, reappraisal, and perceptual acuity as central processes contributing to the pathophysiology of visceral pain.

    16. A single-center, prospective, double-blind, sham-controlled, randomized study of the effect of a vibrating capsule on colonic transit in patients with chronic constipation

      A. D. Nelson, M. Camilleri, A. Acosta, A. Boldingh, I. Busciglio, D. Burton, M. Ryks and A. R. Zinsmeister

      Version of Record online: 8 FEB 2017 | DOI: 10.1111/nmo.13034

      Thumbnail image of graphical abstract

      Patients with functional constipation (Rome III criteria) were randomized to VIBRANT or sham capsule treatment for 8 weeks and underwent scintigraphic colonic transit measurements during week 8. Although there were no group differences between VIBRANT and sham capsule treatment on colonic transit, at least one (and possibly three) of 12 patients receiving the VIBRANT capsule had faster colonic transit. The vibration parameters to accelerate colonic transit in patients with functional constipation require further optimization.

    17. Angiotensin II type II receptors and colonic dysmotility in 2,4-dinitrofluorobenzenesulfonic acid-induced colitis in rats

      M. G. Zizzo, M. Auteri, A. Amato, G. Caldara, D. Nuzzo, M. Di Carlo and R. Serio

      Version of Record online: 3 FEB 2017 | DOI: 10.1111/nmo.13019

      Thumbnail image of graphical abstract

      Our objective was to investigate in rat 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis the functionality of RAS and its contribution to colonic dysmotility. Results indicate that AT1 receptors mediate Angiotensin II contractile responses in rat colon. During inflammation a recruitment of Angiotensin II AT2 receptors would counteract AT1-contractile activity. A tonic activation of AT2 receptors would contribute to the general reduction in muscle contractility during experimental inflammation. A role for enteric neurons and NO is also suggested.

    18. Clinical application of a gadolinium-based capsule as an MRI contrast agent in slow transit constipation diagnostics

      M. Zhi, Z. Zhou, H. Chen, F. Xiong, J. Huang, H. He, M. Zhang, M. Su, X. Gao and P. Hu

      Version of Record online: 1 FEB 2017 | DOI: 10.1111/nmo.13020

      Thumbnail image of graphical abstract

      As a traditional method for the assessment of colon dynamics, radio-opaque markers (ROMs) are limited in clinical use because of their ionizing radiation. We compared the accuracy and applicability of gadolinium-based capsules with ROMs in the measurement of colon dynamics in healthy controls and slow transit constipation (STC) patients. The assessment results of gadolinium-based capsules were in consonance with ROMs. As a MRI contrast label, gadolinium-based capsules exhibit results comparable to ROMs in colon motility measurements.

    19. Waist to hip ratio is a better predictor of esophageal acid exposure than body mass index

      C. Ringhofer, J. Lenglinger, M. Riegler, I. Kristo, A. Kainz and S. F. Schoppmann

      Version of Record online: 29 JAN 2017 | DOI: 10.1111/nmo.13033

      Thumbnail image of graphical abstract

      WHR is associated with the mean clearance time of acid from the distal esophagus (lct, logarithm of mean acid clearance time; hwr, waist to hip ratio)

    20. Normal values of esophageal pressure responses to a rapid drink challenge test in healthy subjects: results of a multicenter study

      I. Marin, D. Cisternas, L. Abrao, E. Lemme, C. Bilder, A. Ditaranto, R. Coello, A. Hani, A. M. Leguizamo, A. Meixueiro, J. Remes-Troche, M. A. Zavala, A. Ruiz de León, J. Perez de la Serna, M. A. Valdovinos and J. Serra

      Version of Record online: 29 JAN 2017 | DOI: 10.1111/nmo.13021

      Thumbnail image of graphical abstract

      The range of normal pressure responses during a rapid drink challenge test has been established in a multicenter study using high-resolution manometry. During multiple swallow, there is a complete inhibition of pressure activity in the esophageal body and a low-pressure gradient across the esophagogastric junction. Complete bolus clearance occurs soon after multiple water swallow stops despite no evident postswallow peristaltic activity is common.

    21. Brain networks associated with cognitive and hedonic responses to a meal

      T. Pribic, L. Kilpatrick, B. Ciccantelli, C. Malagelada, A. Accarino, A. Rovira, D. Pareto, E. Mayer and F. Azpiroz

      Version of Record online: 23 JAN 2017 | DOI: 10.1111/nmo.13031

      Thumbnail image of graphical abstract

      Meal ingestion induces cognitive and hedonic sensations, and our aim was to identify brain networks related to these sensations. Perceptual and emotional responses to food intake are related to brain connectivity in defined functional networks. Brain imaging may provide objective biomarkers of subjective effects of meal ingestion.

    22. Methods of anorectal manometry vary widely in clinical practice: Results from an international survey

      E. V. Carrington, H. Heinrich, C. H. Knowles, S. S. Rao, M. Fox, S. M. Scott and The International Anorectal Physiology Working Party Group (IAPWG)

      Version of Record online: 18 JAN 2017 | DOI: 10.1111/nmo.13016

      Thumbnail image of graphical abstract

      This survey shows that there is significant discrepancy in methods for data acquisition, analysis, and interpretation of ARM. This is likely to impact clinical interpretation, transfer of data between institutions, and research collaboration. There is a need for expert international co-operation to standardize ARM.

    23. A baseline impedance analysis in neurologically impaired children: A potent parameter for estimating the condition of the esophageal mucosa

      S. Fukahori, M. Yagi, S. Ishii, K. Asagiri, N. Saikusa, N. Hashizume, M. Yoshida, D. Masui, N. Komatsuzaki, N. Higashidate, H. Nakahara and Y. Tanaka

      Version of Record online: 13 JAN 2017 | DOI: 10.1111/nmo.13012

      Thumbnail image of graphical abstract

      The present study suggested that NI children with reflux esophagitis were likely to suffer mucosal damage up to the proximal esophagus and cut-off BI values may help estimate the presence of reflux esophagitis. BI is a potent parameter reflecting the esophageal mucosal damage in NI children who have difficulty in undergoing endoscopic examinations.


    1. Gastrointestinal disorders in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type: a review for the gastroenterologist

      A. B. Beckers, D. Keszthelyi, A. Fikree, L. Vork, A. Masclee, A. D. Farmer and Q. Aziz

      Version of Record online: 13 JAN 2017 | DOI: 10.1111/nmo.13013

      Thumbnail image of graphical abstract

      In this review article, we examine the nature of gastrointestinal symptoms and their underlying pathophysiology in JHS/EDS-HT and consider the clinical implications of the diagnosis and treatment of this syndrome for practicing clinicians in gastroenterology.

    2. Established and emerging methods for assessment of small and large intestinal motility

      D. Grønlund, J. L. Poulsen, T. H. Sandberg, A. E. Olesen, A. Madzak, K. Krogh, J. B. Frøkjær and A. M. Drewes

      Version of Record online: 13 JAN 2017 | DOI: 10.1111/nmo.13008

      Thumbnail image of graphical abstract

      This review outlines well-established and emerging methods to evaluate small bowel and colonic motility in clinical settings and in research.


    1. Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum

      M. Grover, C. E. Bernard, P. J. Pasricha, H. P. Parkman, S. J. Gibbons, J. Tonascia, K. L. Koch, R. W. McCallum, I. Sarosiek, W. L. Hasler, L. A. B. Nguyen, T. L. Abell, W. J. Snape, M. L. Kendrick, T. A. Kellogg, T. J. McKenzie, F. A. Hamilton, G. Farrugia and NIDDK Gastroparesis Clinical Research Consortium (GpCRC)

      Version of Record online: 9 JAN 2017 | DOI: 10.1111/nmo.13018

      Thumbnail image of graphical abstract

      Animal studies have highlighted an important role of macrophages in development of delayed gastric emptying. However, their role in human gastroparesis is unclear. Upon assessment of full thickness gastric antrum biopsies, both diabetic and idiopathic gastroparesis patients showed a loss of CD206-positive anti-inflammatory macrophages as compared to controls. This correlated with loss of ICC suggesting a role of innate immune cells in pathophysiology of human gastroparesis.

    2. Could the peristaltic transition zone be caused by non-uniform esophageal muscle fiber architecture? A simulation study

      W. Kou, J. E. Pandolfino, P. J. Kahrilas and N. A. Patankar

      Version of Record online: 5 JAN 2017 | DOI: 10.1111/nmo.13022

      Thumbnail image of graphical abstract

      The effect of varied muscle fiber architecture on esophageal peristalsis was studied based on a fully coupled computational model. Results show that helical fiber architecture featured lesser wall stress and higher distensibility. Non-uniform fiber architecture and dual contraction waves featured a pressure trough between two high-pressure segments. The peristaltic transition zone may be attributable to non-uniform muscle fiber architecture and/or dual contraction waves.

  10. Review Articles

    1. Neuroimmune factors in functional gastrointestinal disorders: A focus on irritable bowel syndrome

      G. E. Boeckxstaens and M. M. Wouters

      Version of Record online: 27 DEC 2016 | DOI: 10.1111/nmo.13007

      Thumbnail image of graphical abstract

      Abnormal abdominal pain perception is the most bothersome and difficult to treat symptom of functional gastrointestinal disorders. Peripheral activation and sensitization of sensory afferent nerve endings by pro-inflammatory mediators can lead to aberrant neuroimmune interactions and visceral hypersensitivity. In IBS, pronociceptive mechanisms seem to be upregulated, while antinociceptive mechanisms are downregulated. A better understanding of the factors involved may provide novel therapeutic strategies that elevate symptoms and potentially even cure a subpopulation of patients with IBS.

  11. Hot Topic

    1. Cyclic Vomiting Syndrome is characterized by altered functional brain connectivity of the insular cortex: a cross-comparison with migraine and healthy adults

      D.-M. Ellingsen, R. G. Garcia, J. Lee, R. L. Lin, J. Kim, A. H. Thurler, S. Castel, L. Dimisko, B. R. Rosen, N. Hadjikhani, B. Kuo and V. Napadow

      Version of Record online: 1 DEC 2016 | DOI: 10.1111/nmo.13004

      Thumbnail image of graphical abstract

      Cyclic Vomiting Syndrome (CVS) and Episodic Migraine (MIG) may share pathophysiology, but no studies have yet compared these conditions. We found that the mid-posterior insula, a key region for viscero-sensation, shows diminished brain functional connectivity with the Sensorimotor Network in both CVS and MIG, but increased connectivity to the Salience Network for CVS only, compared to age- and sex-matched healthy controls. The results point to both CVS-unique and potentially shared pathophysiology between CVS and episodic migraine.


  1. 1 - 63