Publications by authors named "Anna Accarino"

49 Publications

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

Neurogastroenterol Motil 2021 09;33(9):e14238

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1111/nmo.14238DOI Listing
September 2021

Propagation patterns of jejunal motor activity measured by high-resolution water-perfused manometry.

Neurogastroenterol Motil 2021 12 11;33(12):e14240. Epub 2021 Aug 11.

Digestive System Research Unit, University Hospital Vall d'Hebron Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Spain.

Background: The manometric diagnosis of severe intestinal dysmotility is performed at most institutions using catheters with 2-8 sensors 5-10 cm apart. The recent application of high-resolution manometry catheters with closely spaced sensors to other gut segments has been highly successful. The objective of the present study was to determine the feasibility of a jejunal high-resolution manometry method and to carry out a descriptive analysis of normal jejunal motor function.

Methods: A 36-channel high-resolution water-perfused manometry catheter (MMS-Laborie, Enschede, The Netherlands) was orally placed in the jejunum of 18 healthy subjects (10 men, eight women; 21-38 age range). Intestinal motility was recorded during 5 h, 3 during fasting, and 2 after a 450 kcal solid-liquid meal. Analysis of motility patterns was supported by computerized tools.

Key Results: All healthy subjects except one showed at least one complete migrating motor complex during the 3 h fasting period. Phase III activity lasted 5 ± 1 min and migrated aborally at a velocity of 7 ± 3 cm/min. High-resolution spatial analysis showed that during phase III each individual contraction propagated rapidly (75 ± 37 cm/min) over a 32 ± 10 cm segment of the jejunum. During phase II, most contractile activity corresponded to propagated contractile events which increased in frequency from early to late phase II (0.5 ± 0.9 vs 2.5 ± 1.3 events/10 min, respectively; p < 0.001). After meal ingestion, non-propagated activity increased, whereas propagated events were less frequent than during late phase II.

Conclusions & Inferences: Jejunal motility analysis with high-resolution manometry identifies propagated contractile patterns which are not apparent with conventional manometric catheters.
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http://dx.doi.org/10.1111/nmo.14240DOI Listing
December 2021

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

United European Gastroenterol J 2021 04;9(3):307-331

Gastroenterology Unit, Departmento of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.

Background: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis.

Methods: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.

Results: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
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http://dx.doi.org/10.1002/ueg2.12061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259261PMC
April 2021

Abdominothoracic Postural Tone Influences the Sensations Induced by Meal Ingestion.

Nutrients 2021 Feb 18;13(2). Epub 2021 Feb 18.

Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Departament de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain.

Postprandial objective abdominal distention is frequently associated with a subjective sensation of abdominal bloating, but the relation between both complaints is unknown. While the bloating sensation has a visceral origin, abdominal distention is a behavioral somatic response, involving contraction and descent of the diaphragm with protrusion of the anterior abdominal wall. Our aim was to determine whether abdominal distention influences digestive sensations. In 16 healthy women we investigated the effect of intentional abdominal distention on experimentally induced bloating sensation (by a meal overload). Participants were first taught to produce diaphragmatic contraction and visible abdominal distention. After a meal overload, sensations of bloating (0 to 10) and digestive well-being (-5 to + 5) were measured during 30-s. maneuvers alternating diaphragmatic contraction and diaphragmatic relaxation. Compared to diaphragmatic relaxation, diaphragmatic contraction was associated with diaphragmatic descent (by 21 + 3 mm; < 0.001), objective abdominal distension (32 + 5 mm girth increase; = 0.001), more intense sensation of bloating (7.3 + 0.4 vs. 8.0 + 0.4 score; = 0.010) and lower digestive well-being (-0.9 + 0.5 vs. -1.9 + 0.5 score; = 0.028). These results indicate that somatic postural tone underlying abdominal distention worsens the perception of visceral sensations (ClinicalTrials.gov ID: NCT04691882).
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http://dx.doi.org/10.3390/nu13020658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922384PMC
February 2021

Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy.

Am J Physiol Gastrointest Liver Physiol 2021 05 3;320(5):G768-G779. Epub 2021 Mar 3.

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by thymidine phosphorylase (TP) enzyme defect. As gastrointestinal changes do not revert in patients undergone TP replacement therapy, one can postulate that other unexplored mechanisms contribute to MNGIE pathophysiology. Hence, we focused on the local TP angiogenic potential that has never been considered in MNGIE. In this study, we investigated the enteric submucosal microvasculature and the effect of hypoxia on fibrosis and enteric neurons density in jejunal full-thickness biopsies collected from patients with MNGIE. Orcein staining was used to count blood vessels based on their size. Fibrosis was assessed using the Sirius Red and Fast Green method. Hypoxia and neoangiogenesis were determined via hypoxia-inducible-factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) protein expression, respectively. Neuron-specific enolase was used to label enteric neurons. Compared with controls, patients with MNGIE showed a decreased area of vascular tissue, but a twofold increase of submucosal vessels/mm with increased small size and decreased medium and large size vessels. VEGF positive vessels, fibrosis index, and HIF-1α protein expression were increased, whereas there was a diminished thickness of the longitudinal muscle layer with an increased interganglionic distance and reduced number of myenteric neurons. We demonstrated the occurrence of an angiopathy in the GI tract of patients with MNGIE. Neoangiogenetic changes, as detected by the abundance of small size vessels in the jejunal submucosa, along with hypoxia provide a morphological basis to explain neuromuscular alterations, vasculature breakdown, and ischemic abnormalities in MNGIE. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is characterized by a genetically driven defect of thymidine phosphorylase, a multitask enzyme playing a role also in angiogenesis. Indeed, major gastrointestinal bleedings are life-threatening complications of MNGIE. Thus, we focused on jejunal submucosal vasculature and showed intestinal microangiopathy as a novel feature occurring in this disease. Notably, vascular changes were associated with neuromuscular abnormalities, which may explain gut dysfunction and help to develop future therapeutic approaches in MNGIE.
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http://dx.doi.org/10.1152/ajpgi.00047.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202202PMC
May 2021

Different responses of the blockade of the P2Y1 receptor with BPTU in human and porcine intestinal tissues and in cell cultures.

Neurogastroenterol Motil 2021 07 22;33(7):e14101. Epub 2021 Feb 22.

Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background: Gastrointestinal smooth muscle relaxation is accomplished by activation of P2Y receptors, therefore this receptor plays an important role in regulation of gut motility. Recently, BPTU was developed as a negative allosteric modulator of the P2Y receptor. Accordingly, the aim of this study was to assess the effect of BPTU on purinergic neurotransmission in pig and human gastrointestinal tissues.

Methods: Ca imaging in tSA201 cells that express the human P2Y receptor, organ bath and microelectrodes in tissues were used to evaluate the effects of BPTU on purinergic responses.

Key Results: BPTU concentration dependently (0.1 and 1 µmol L ) inhibited the rise in intracellular Ca evoked by ADP in tSA201 cells. In the pig small intestine, 30 µmol L BPTU reduced the fast inhibitory junction potential by 80%. Smooth muscle relaxations induced by electrical field stimulation were reduced both in pig ileum (EC  = 6 µmol L ) and colon (EC  = 35 µmol L ), but high concentrations of BPTU (up to 100 µmol L ) had no effect on human colonic muscle. MRS2500 (1 µmol L ) abolished all responses. Finally, 10 µmol L ADPβS inhibited spontaneous motility and this was partially reversed by 30 µmol L BPTU in pig, but not human colonic tissue and abolished by MRS2500 (1 µmol L ).

Conclusions & Inferences: BPTU blocks purinergic responses elicited via P2Y receptors in cell cultures and in pig gastrointestinal tissue. However, the concentrations needed are higher in pig tissue compared to cell cultures and BPTU was ineffective in human colonic tissue.
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http://dx.doi.org/10.1111/nmo.14101DOI Listing
July 2021

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network.

J Inherit Metab Dis 2021 03 8;44(2):376-387. Epub 2020 Sep 8.

Department of Clinical Movement Neurosciences, Royal Free Campus, University College of London, Queen Square Institute of Neurology, London, UK.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by TYMP mutations and thymidine phosphorylase (TP) deficiency. Thymidine and deoxyuridine accumulate impairing the mitochondrial DNA maintenance and integrity. Clinically, patients show severe and progressive gastrointestinal and neurological manifestations. The onset typically occurs in the second decade of life and mean age at death is 37 years. Signs and symptoms of MNGIE are heterogeneous and confirmatory diagnostic tests are not routinely performed by most laboratories, accounting for common misdiagnosis. Factors predictive of progression and appropriate tests for monitoring are still undefined. Several treatment options showed promising results in restoring the biochemical imbalance of MNGIE. The lack of controlled studies with appropriate follow-up accounts for the limited evidence informing diagnostic and therapeutic choices. The International Consensus Conference (ICC) on MNGIE, held in Bologna, Italy, on 30 March to 31 March 2019, aimed at an evidence-based consensus on diagnosis, prognosis, and treatment of MNGIE among experts, patients, caregivers and other stakeholders involved in caring the condition. The conference was conducted according to the National Institute of Health Consensus Conference methodology. A consensus development panel formulated a set of statements and proposed a research agenda. Specifically, the ICC produced recommendations on: (a) diagnostic pathway; (b) prognosis and the main predictors of disease progression; (c) efficacy and safety of treatments; and (f) research priorities on diagnosis, prognosis, and treatment. The Bologna ICC on diagnosis, management and treatment of MNGIE provided evidence-based guidance for clinicians incorporating patients' values and preferences.
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http://dx.doi.org/10.1002/jimd.12300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399867PMC
March 2021

Recommendations of the Spanish Association of Neurogastroenterology and Motility (ASENEM) to restart the activity of gastrintestinal motility laboratories after the state of alarm called due to the Covid-19 pandemic.

Gastroenterol Hepatol 2020 Oct 18;43(8):485-496. Epub 2020 Jun 18.

Unidad de Pruebas Funcionales Digestivas, Servicio de Aparato Digestivo, Hospital General Vall d́Hebron, Barcelona, España; Universidad Autónoma de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, España.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was responsible for the outbreak of the 2019 coronavirus disease (COVID-19), which is now considered as a pandemic. The prevention strategies adopted have included social distancing measures and the modification, reduction or interruption of a large proportion of routine healthcare activity. This has had a significant impact on the care provided in Gastrointestinal Motility Units. Having passed the peak, in terms of mortality and infections, a gradual reduction in transmission figures has been observed in Spain and other European countries. The risk of reactivation, however, remains high, so it is necessary to have a plan in place that allows healthcare centres to safely resume, for their patients and professionals, instrumental examinations linked to the management of motor pathology. Based on the available scientific evidence and the consensus of a panel of experts, the Spanish Association of Neurogastroenterology and Motility (ASENEM) has drawn up a series of practical recommendations, which have been adapted to the risks inherent in each activity. These include individual protection proposals, as well as organisational and structural measures, which are conceived to allow for the gradual resumption of examinations while minimising the possibility of contagion.
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http://dx.doi.org/10.1016/j.gastrohep.2020.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301085PMC
October 2020

European Society for Neurogastroenterology and Motility recommendations for conducting gastrointestinal motility and function testing in the recovery phase of the COVID-19 pandemic.

Neurogastroenterol Motil 2020 07;32(7):e13930

Department of Digestive Diseases and Internal Medicine, University of Bologna, St Orsola-Malpighi Hospital, Bologna, Italy.

Background: During the peak of the COronaVIrus Disease 2019 (COVID-19) pandemic, care for patients with gastrointestinal motility and functional disorders was largely suspended. In the recovery phases of the pandemic, non-urgent medical care is resumed, but there is a lack of guidance for restarting and safely conducting motility and function testing. Breath tests and insertion of manometry and pH-monitoring probes carry a risk of SARS-CoV-2 spread through droplet formation.

Methods: A panel of experts from the European Society for Neurogastroenterology and Motility (ESNM) evaluated emerging national and single-center recommendations to provide the best current evidence and a pragmatic approach to ensure the safe conduct of motility and function testing for both healthcare professionals and patients.

Results: At a general level, this involves evaluation of the urgency of the procedure, evaluation of the infectious risk associated with the patient, the investigation and the healthcare professional(s) involved, provision of the test planning and test units, education and training of staff, and use of personnel protection equipment. Additional guidance is provided for specific procedures such as esophageal manometry, pH monitoring, and breath tests.

Conclusions And Inferences: The ESNM guidelines provide pragmatic and appropriate guidance for the safe conduct of motility and function testing in the COVID-19 pandemic and early recovery phase.
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http://dx.doi.org/10.1111/nmo.13930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300574PMC
July 2020

Sex Differences and Commonalities in the Impact of a Palatable Meal on Thalamic and Insular Connectivity.

Nutrients 2020 Jun 1;12(6). Epub 2020 Jun 1.

Division of Digestive Diseases, G Oppenheimer Center for Neurobiology of Stress and Resilience, Los Angeles, CA 90095, USA.

The neural mechanisms underlying subjective responses to meal ingestion remain incompletely understood. We previously showed in healthy men an increase in thalamocortical, and a decrease in insular-cortical connectivity in response to a palatable meal. As sex is increasingly recognized as an important biological variable, we aimed to evaluate sex differences and commonalities in the impact of a well-liked meal on thalamic and anterior insular connectivity in healthy individuals. Participants (20 women and 20 age-matched men) underwent resting-state magnetic resonance imaging (rsMRI) before and after ingesting a palatable meal. In general, the insula showed extensive postprandial reductions in connectivity with sensorimotor and prefrontal cortices, while the thalamus showed increases in connectivity with insular, frontal, and occipital cortices, in both women and men. However, reductions in insular connectivity were more prominent in men, and were related to changes in meal-related sensations (satiety and digestive well-being) in men only. In contrast, increases in thalamic connectivity were more prominent in women, and were related to changes in satiety and digestive well-being in women only. These results suggest that brain imaging may provide objective and sex-specific biomarkers of the subjective feelings associated with meal ingestion.
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http://dx.doi.org/10.3390/nu12061627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352462PMC
June 2020

Motor dysfunction of the gut in cystic fibrosis.

Neurogastroenterol Motil 2020 09 31;32(9):e13883. Epub 2020 May 31.

Digestive System Research Unit, University Hospital Vall d'Hebron; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain.

Background: Cystic fibrosis (CF) is a multisystem disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Cystic fibrosis transmembrane conductance regulator is extensively expressed in the intestine and has an important role in the regulation of the viscosity and pH of gut secretions. Several studies have reported a delay in small bowel and colonic transit times in patients with CF which have been attributed to the secretory dysfunction. Our aim was to determine whether intestinal contractility is affected in these patients.

Methods: Consecutive patients with CF referred to our institution between 2014 and 2017 (n = 16) were prospectively investigated using automated non-invasive techniques for morpho-functional evaluation of the gut developed in our laboratory. On separate days, intraluminal images of the gut were obtained by capsule endoscopy and external images by abdominal MRI. Analysis of images (endoluminal and external) was performed with original, previously validated programs based on computer vision and machine learning techniques and compared with age- and sex-matched controls.

Key Results: Patients with CF exhibited important reduction in contractile activity and increased retention of static turbid luminal content in the small bowel by endoluminal image analysis. Morpho-volumetric analysis of MRI images found increased ileo-colonic volumes in CF. Significant correlations between abnormalities detected by intraluminal and external imaging techniques were found. The presence and severity of digestive symptoms were not related to abnormal gut function.

Conclusion And Inferences: Impaired transit and pooling of gut contents in patients with CF is associated with impaired intestinal motility.
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http://dx.doi.org/10.1111/nmo.13883DOI Listing
September 2020

Testing the Food Experience in Healthy Human Volunteers: a Proof-of-Concept Study.

J Gastrointestin Liver Dis 2020 Mar 13;29(1):65-68. Epub 2020 Mar 13.

Neuroradiology Section, Radiology Department, University Hospital Vall d'Hebron, Barcelona, Spain.

Background And Aims: For a healthy food to be introduced to the consumer's diet, it has to be attractive, yet testing for food acceptance and the sensory postprandial responses is still not standardized. The main objective of this study was to demonstrate that healthier foods can be obtained without impact on the responses to ingestion.

Methods: A randomized, cross-over, double-blind, pilot study in non-obese, healthy men (n=8) comparing the responses to a standard sausage rich in animal fat (mortadella) versus a modified product based on a plant-derived fat analogue and an aroma. Palatability and postprandial sensations were measured on 10 cm scales and brain activity was evaluated by functional magnetic resonance imaging before and after each meal on separate days.

Results: Both meals were rated equally palatable and induced the same degree of homeostatic sensations (satiety, fullness) with a similar hedonic dimension (improved mood and digestive well-being). Both meals induced similar changes in brain connectivity: decreased activity in the frontal-parietal, basal ganglia and thalamus, visual occipital, sensory-motor, temporal superior and in the "default-mode" networks, while increased activity was detected in the network associated with white matter.

Conclusion: A substantial improvement in the nutritional profile of food can be achieved without affecting the responses to ingestion.
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http://dx.doi.org/10.15403/jgld-806DOI Listing
March 2020

A Fermented Milk Product with CNCM I-2494 and Lactic Acid Bacteria Improves Gastrointestinal Comfort in Response to a Challenge Diet Rich in Fermentable Residues in Healthy Subjects.

Nutrients 2020 Jan 25;12(2). Epub 2020 Jan 25.

Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Departament de Medicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain.

Background: Healthy plant-based diets rich in fermentable residues may induce gas-related symptoms. Our aim was to determine the potential of a fermented milk product with probiotics in improving digestive comfort with such diets.

Methods: In an open design, a 3-day high-residue diet was administered to healthy subjects ( = 74 included, = 63 completed) before and following 28 days consumption of a fermented milk product (FMP) containing subsp. CNCM I-2494 and lactic acid bacteria.

Main Outcomes: digestive sensations, number of daytime anal gas evacuations, and gas volume evacuated during 4 h after a probe meal.

Results: As compared to the habitual diet, the high-residue diet induced gas-related symptoms (flatulence score 4.9 vs. 1.2; ≤ 0.0001), increased the daily number of anal gas evacuations (20.7 vs. 8.7; < 0.0001), and impaired digestive well-being (1.0 vs. 3.4; < 0.05). FMP consumption reduced flatulence sensation (by -1.7 [-1.9; -1.6]; < 0.0001), reduced the number of daily evacuations (by -5.8 [-6.5; -5.1]; < 0.0001), and improved digestive well-being (by +0.6 [+0.4; +0.7]; < 0.05). FMP consumption did not affect the gas volume evacuated after a probe meal.

Conclusion: In healthy subjects, consumption of a FMP containing CNCM I-2494 and lactic acid bacteria improves the tolerance of a flatulogenic diet by subjective and objective criteria (sensations and number of anal gas evacuations, respectively).
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http://dx.doi.org/10.3390/nu12020320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071254PMC
January 2020

Correction of Dyssynergic Defecation, but Not Fiber Supplementation, Reduces Symptoms of Functional Dyspepsia in Patients With Constipation in a Randomized Trial.

Clin Gastroenterol Hepatol 2020 10 4;18(11):2463-2470.e1. Epub 2019 Dec 4.

Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Electronic address:

Background & Aims: Patients with functional dyspepsia are believed to have increased sensitivity of the gastrointestinal tract, and some also have functional constipation. We investigated whether in patients with functional dyspepsia, correction of dyssynergic defecation can reduce postprandial fullness.

Methods: We performed a parallel trial at 2 referral centers in Spain, from June 2016 through January 2018 of 50 patients who fulfilled the Rome IV criteria for functional dyspepsia with postprandial distress syndrome and functional constipation and dyssynergic defecation. After a 2-week pretreatment phase, the patients were randomly assigned to groups that learned to correct dyssynergic defecation (2-3 sessions of biofeedback combined with instructions for daily exercise; n = 25) or received dietary fiber supplementation (3.5 g plantago ovata per day; n = 25) for 4 weeks. The primary outcome was change in postprandial abdominal fullness, measured daily on a scale of 0-10, during the last 7 days treatment phase vs the last 7 days of the pretreatment phase. Anal gas evacuations were measured (by an event marker) during the last 2 days of the pretreatment vs treatment phases.

Results: Biofeedback treatment corrected dyssynergic defecation in 19/25 patients; corrected dyssynergic defection reduced postprandial fullness by 22%±1% in these patients (P < .001), and reduced the number of anal evacuations by 21%±8% (P = .009). Fiber supplementation did not reduce postprandial fullness or anal evacuations (P ≤ .023 between groups for both parameters in the intent to treat analysis).

Conclusions: Diagnosis and correction of dyssynergic defecation reduces dyspeptic symptoms by more than 20% in patients with functional dyspepsia and associated constipation. Dietary fiber supplementation does not reduce symptoms in these patients. ClinicalTrials.gov no: NCT02956187.
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http://dx.doi.org/10.1016/j.cgh.2019.11.048DOI Listing
October 2020

Enteric neuron density correlates with clinical features of severe gut dysmotility.

Am J Physiol Gastrointest Liver Physiol 2019 12 23;317(6):G793-G801. Epub 2019 Sep 23.

Department of Medical Sciences, University of Ferrara, Ferrara, Italy.

Gastrointestinal (GI) symptoms can originate from severe dysmotility due to enteric neuropathies. Current methods used to demonstrate enteric neuropathies are based mainly on classic qualitative histopathological/immunohistochemical evaluation. This study was designed to identify an objective morphometric method for paraffin-embedded tissue samples to quantify the interganglionic distance between neighboring myenteric ganglia immunoreactive for neuron-specific enolase, as well as the number of myenteric and submucosal neuronal cell bodies/ganglion in jejunal specimens of patients with severe GI dysmotility. Jejunal full-thickness biopsies were collected from 32 patients (22 females; 16-77 yr) with well-characterized severe dysmotility and 8 controls (4 females; 47-73 yr). A symptom questionnaire was filled before surgery. Mann-Whitney test, Kruskal-Wallis coupled with Dunn's posttest and nonparametric linear regression tests were used for analyzing morphometric data and clinical correlations, respectively. Compared with controls, patients with severe dysmotility exhibited a significant increase in myenteric interganglionic distance ( = 0.0005) along with a decrease in the number of myenteric ( < 0.00001) and submucosal ( < 0.0004) neurons. A 50% reduction in the number of submucosal and myenteric neurons correlated with an increased interganglionic distance and severity of dysmotility. Our study proposes a relatively simple tool that can be applied for quantitative evaluation of paraffin sections from patients with severe dysmotility. The finding of an increased interganglionic distance may aid diagnosis and limit the direct quantitative analysis of neurons per ganglion in patients with an interganglionic distance within the control range. Enteric neuropathies are challenging conditions characterized by a severe impairment of gut physiology, including motility. An accurate, unambiguous assessment of enteric neurons provided by quantitative analysis of routine paraffin sections may help to define neuropathy-related gut dysmotility. We showed that patients with severe gut dysmotility exhibited an increased interganglionic distance associated with a decreased number of myenteric and submucosal neurons, which correlated with symptoms and clinical manifestations of deranged intestinal motility.
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http://dx.doi.org/10.1152/ajpgi.00199.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962493PMC
December 2019

Abdominal distension after eating lettuce: The role of intestinal gas evaluated in vitro and by abdominal CT imaging.

Neurogastroenterol Motil 2019 12 11;31(12):e13703. Epub 2019 Aug 11.

Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain.

Background: Some patients complain that eating lettuce, gives them gas and abdominal distention. Our aim was to determine to what extent the patients' assertion is sustained by evidence.

Methods: An in vitro study measured the amount of gas produced during the process of fermentation by a preparation of human colonic microbiota (n = 3) of predigested lettuce, as compared to beans, a high gas-releasing substrate, to meat, a low gas-releasing substrate, and to a nutrient-free negative control. A clinical study in patients complaining of abdominal distention after eating lettuce (n = 12) measured the amount of intestinal gas and the morphometric configuration of the abdominal cavity in abdominal CT scans during an episode of lettuce-induced distension as compared to basal conditions.

Key Results: Gas production by microbiota fermentation of lettuce in vitro was similar to that of meat (P = .44), lower than that of beans (by 78 ± 15%; P < .001) and higher than with the nutrient-free control (by 25 ± 19%; P = .05). Patients complaining of abdominal distension after eating lettuce exhibited an increase in girth (35 ± 3 mm larger than basal; P < .001) without significant increase in colonic gas content (39 ± 4 mL increase; P = .071); abdominal distension was related to a descent of the diaphragm (by 7 ± 3 mm; P = .027) with redistribution of normal abdominal contents.

Conclusion And Inferences: Lettuce is a low gas-releasing substrate for microbiota fermentation and lettuce-induced abdominal distension is produced by an uncoordinated activity of the abdominal walls. Correction of the somatic response might be more effective than the current dietary restriction strategy.
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http://dx.doi.org/10.1111/nmo.13703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899808PMC
December 2019

Gut epithelial and vascular barrier abnormalities in patients with chronic intestinal pseudo-obstruction.

Neurogastroenterol Motil 2019 08 29;31(8):e13652. Epub 2019 May 29.

Department of Medical Sciences, University of Ferrara, Ferrara, Italy.

Background: Chronic intestinal pseudo-obstruction (CIPO) is a rare condition due to severe impairment of gut motility responsible for recurrent subocclusive episodes. Although neuromuscular-glial-ICC abnormalities represent the main pathogenetic mechanism, the pathophysiology of CIPO remains poorly understood. Intestinal epithelial and vascular endothelial barrier (IEVB) abnormalities can contribute to neuroepithelial changes by allowing passage of harmful substances.

Methods: To test retrospectively whether IEVB defects occur in patients with CIPO, we measured the jejunal protein expression of the major tight junction (TJ) components. CIPO patients were subdivided according to gut neuromuscular histopathology: apparently normal (AN); with inflammation (INF); or with degenerative alterations (DEG). The presence of occludin/claudin oligomers (index of TJ assembly), the amount of occludin, claudin-4, and zonula occludens-1 (ZO-1), and the expression of vasoactive intestinal polypeptide (VIP) and glial fibrillary acidic protein (GFAP) immunoreactivities were evaluated on jejunal full-thickness biopsies using Western blot.

Key Results: Oligomers were absent in the 73% of CIPO. Total occludin decreased in CIPO with AN and INF changes. Claudin-4 was upregulated in CIPO with INF and DEG features. ZO-1 and VIP expression decreased selectively in DEG group. GFAP increased in CIPO regardless the histopathological phenotype.

Conclusions & Inferences: The absence of oligomers demonstrated in our study suggests that IEBV is altered in CIPO. The mechanism leading to oligomerization is occludin-dependent in AN and INF, whereas is ZO-1-dependent in DEG. Our study provides support to IEVB abnormalities contributing to CIPO clinical and histopathological features.
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http://dx.doi.org/10.1111/nmo.13652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639131PMC
August 2019

Biological Response to Meal Ingestion: Gender Differences.

Nutrients 2019 Mar 26;11(3). Epub 2019 Mar 26.

Digestive System Research Unit, University Hospital Vall d'Hebron; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Departament de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain.

In a previous study, we demonstrated that women enjoyed and tolerated lower meal loads than men. Hence, we hypothesized that with the same meal load, their postprandial response is more pronounced than in men. We performed a randomized parallel trial in 12 women and 12 men comparing the postprandial responses to a palatable comfort meal. We measured homeostatic sensations (hunger/satiety, fullness) and hedonic sensations (digestive well-being, mood) on 10 cm scales, vagal tone by heart ratio variability and the metabolomic profile before and after meal ingestion. Gender differences were analyzed by repeated measures ANCOVA. Overall ( = 24), ingestion of the probe meal induced satiation, fullness, digestive well-being and improved mood (main time-effect ≤ 0.005 for all). Women exhibited a more intense sensory experience, specially more postprandial fullness, than men [main gender-effect F (1, 21) = 7.14; = 0.014]; hedonic responses in women also tended to be stronger than in men. Women exhibited more pronounced effects on vagal tone [main gender-effect F (1, 21) = 5.5; = 0.029] and a different lipoprotein response than men. In conclusion, our data indicate that gender influences the responses to meal ingestion, and these differences may explain the predisposition and higher incidence in women of meal-related functional disorders.
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http://dx.doi.org/10.3390/nu11030702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471145PMC
March 2019

Influence of Eating Schedule on the Postprandial Response: Gender Differences.

Nutrients 2019 Feb 14;11(2). Epub 2019 Feb 14.

Departament de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain.

Ingestion of a meal induces conscious sensations depending of the characteristics of the meal and the predisposition of the eater. We hypothesized that the eating schedule plays a conditioning role, specifically, that an extemporaneous meal is less rewarding than when eaten at the habitual schedule. We conducted a randomized parallel trial in 10 women and 10 men comparing the responses to a consistent savoury lunch-type meal (stewed beans) eaten at the habitual afternoon schedule or at an unconventional time in the morning. Schedule and gender differences were analyzed by repeated measures analysis of covariance. In women, the sensory experience induced by the probe meal, particularly postprandial satisfaction, was weaker when eaten at an unconventional time for breakfast. Men were resilient to the schedule effect and experienced the same sensations regardless of the timing of ingestion; the effect of the eating schedule was significantly more pronounced in women for fullness (F(1,55) = 14.9; < 0.001), digestive well-being (F(1,36.8) = 22.3; < 0.001), mood (F(1,12.4) = 13.8; < 0.001), and anxiety (F(1,11.9) = 10.9; = 0.001). No differences in the physiological responses induced by the afternoon and morning meals were detected either in women or men. Our data indicate that women are more susceptible to changes in meal schedule than men.
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http://dx.doi.org/10.3390/nu11020401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412254PMC
February 2019

Meal Enjoyment and Tolerance in Women and Men.

Nutrients 2019 Jan 8;11(1). Epub 2019 Jan 8.

Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Departament de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain.

Various conditioning factors influence the sensory response to a meal (inducible factors). We hypothesized that inherent characteristics of the eater (constitutive factors) also play a role. The aim of this proof-of-concept study was to determine the role of gender, as an individual constitutive factor, on the meal-related experience. Randomized parallel trial in 10 women and 10 men, comparing the sensations before, during, and after stepwise ingestion of a comfort meal up to full satiation. Comparisons were performed by repeated Analysis of Covariance (ANCOVA) measures. During stepwise ingestion, satisfaction initially increased up to a peak, and later decreased down to a nadir at the point of full satiation. Interestingly, the amount of food consumed at the well-being peak was lower, and induced significantly less fullness in women than in men. Hence, men required a larger meal load and stronger homeostatic sensations to achieve satisfaction. The same pattern was observed at the level of full satiation: men ate more and still experienced positive well-being, whereas in women, well-being scores dropped below pre-meal level. The effect of gender on the ingestion experience suggests that other constitutive factors of the eater may also influence responses to meals.
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http://dx.doi.org/10.3390/nu11010119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356583PMC
January 2019

Functional neuromuscular impairment in severe intestinal dysmotility.

Neurogastroenterol Motil 2018 12 3;30(12):e13458. Epub 2018 Sep 3.

Department of Cell Biology, Physiology and Immunology and Neurosciences Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background: Chronic intestinal pseudo-obstruction (CIPO) and enteric dysmotility (ED) are severe intestinal motility disorders usually associated with underlying neuromuscular abnormalities.

Objective: To evaluate the in vitro neuromuscular function of patients with severe intestinal motility disorders.

Methods: Full-thickness intestinal biopsies (16 jejunum and 3 ileum) obtained from patients with CIPO (n = 10) and ED (n = 9) were studied using muscle bath and microelectrode techniques. Control samples (n = 6 ileum and n = 6 jejunum) were used to establish the range of normality.

Key Results: Fourteen parameters were defined to assess muscle contractility and nerve-muscle interaction: five to evaluate smooth muscle and interstitial cells of Cajal (ICC) and nine to evaluate inhibitory neuromuscular transmission. For each sample, a parameter was scored 0 if the value was inside the normal range or a value of 1 if it was outside. Patients' samples (CIPO/ED) had more abnormal parameters than controls (P < 0.001 for both jejunum and ileum). Functional abnormalities were found to be heterogeneous. The most prevalent abnormality was a decreased purinergic neuromuscular transmission, which was detected in 43.8% of jejunal samples.

Conclusions And Inferences: Abnormalities of neuromuscular intestinal function are detected in vitro in severe intestinal dysmotility. However, consistent with the heterogeneity of the disease pathophysiology, functional impairment cannot be attributed to a single mechanism. Specifically, defects of purinergic neuromuscular transmission may have an important role in motility disorders of the gastrointestinal tract.
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http://dx.doi.org/10.1111/nmo.13458DOI Listing
December 2018

Metabolomic signature of the postprandial experience.

Neurogastroenterol Motil 2018 12 13;30(12):e13447. Epub 2018 Aug 13.

Digestive System Research Unit, University Hospital Vall d'Hebron, Bellaterra, Spain.

Background: Ingestion of a meal up to maximal tolerance induces unpleasant fullness sensation and changes in circulating metabolites. Our aim was to evaluate the relation between postprandial sensations and the metabolomic responses to a comfort meal.

Methods: In 32 non-obese healthy men, homeostatic sensations (hunger/satiety, fullness), hedonic sensations (digestive well-being, mood), and the metabolomic profile in plasma (low-molecular weight metabolites and lipoprotein profiles) were measured before and 20 minutes after a comfort meal (warm ham and cheese sandwich and juice; total 300 mL; 425 kcal). Perception was measured on 10 cm scales and the metabolomic response by nuclear magnetic resonance spectroscopy.

Key Results: The comfort meal induced homeostatic sensations (satiety and fullness) associated with a positive hedonic reward (enhanced digestive well-being and mood) and a clear change in the metabolomic profile with a sharp discrimination between the pre and postprandial state by a non-supervised principal component analysis. The change in circulating metabolites correlated with the postprandial sensations: the increase in alanine correlated with the increase in fullness (R = 0.50; P = 0.004) and well-being (R = 0.50; P = 0.004); the increase in glucose correlated with the sensation of fullness (R = 0.40; P = 0.023) and enhanced mood (R = 0.41; P = 0.020).

Conclusion And Inferences: Metabolomic changes in the response to a meal may provide an objective index of the postprandial experience, which may have clinical implications in the management of patients with poor meal tolerance or meal-related symptoms.
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http://dx.doi.org/10.1111/nmo.13447DOI Listing
December 2018

Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut Disorders.

Gastroenterology 2018 10 30;155(4):1004-1007. Epub 2018 Jun 30.

Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain. Electronic address:

Prebiotics and diets low in fermentable oligo-, di-, mono-saccharides and polyols (low-FODMAP diet) might reduce symptoms in patients with functional gastrointestinal disorders, despite reports that some nonabsorbable, fermentable meal products (prebiotics) provide substrates for colonic bacteria and thereby increase gas production. We performed a randomized, parallel, double-blind study of patients with functional gastrointestinal disorders with flatulence. We compared the effects of a prebiotic supplement (2.8 g/d Bimuno containing 1.37 g beta-galactooligosaccharide) plus a placebo (Mediterranean-type diet (prebiotic group, n = 19) vs a placebo supplement (2.8 g xylose) plus a diet low in FODMAP (low-FODMAP group, n = 21) for 4 weeks; patients were then followed for 2 weeks. The primary outcome was effects on composition of the fecal microbiota, analyzed by 16S sequencing. Secondary outcomes were intestinal gas production and digestive sensations. After 4 weeks, we observed opposite effects on microbiota in each group, particularly in relation to the abundance of Bifidobacterium sequences (increase in the prebiotic group and decrease in the low-FODMAP group; P = .042), and Bilophila wadsworthia (decrease in the prebiotic group and increase in the low-FODMAP group; P = .050). After 4 weeks, both groups had statistically significant reductions in all symptom scores, except reductions in flatulence and borborygmi were not significant in the prebiotic group. Although the decrease in symptoms persisted for 2 weeks after patients discontinued prebiotic supplementation, symptoms reappeared immediately after patients discontinued the low-FODMAP diet. Intermittent prebiotic administration might therefore be an alternative to dietary restrictions for patients with functional gut symptoms. ClinicalTrials.gov no.: NCT02210572.
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http://dx.doi.org/10.1053/j.gastro.2018.06.045DOI Listing
October 2018

The role of incongruence between the perceived functioning by patients and clinicians in the detection of psychological distress among functional and motor digestive disorders.

J Psychosom Res 2017 08 9;99:112-119. Epub 2017 Jun 9.

Digestive System Research Unit, University Hospital Vall d'Hebron, CIBEREHD, Barcelona, Spain; Departament of Medicine, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain.

Objectives: Previous research on gastrointestinal and other medical conditions has shown the presence of incongruence between self- and clinician-reported functioning and its relation with psychopathology. The main objective of this study was to test whether inconsistencies between clinician- and self-assessed functionality can be used to detect psychopathology among patients diagnosed of motor or functional gastrointestinal disorders.

Methods: One hundred and three patients from a gastroenterology inpatient unit were included in this study. All patients underwent clinical assessment, including intestinal manometry, Rome III criteria for functional gastrointestinal disorders, and psychological and psychiatric evaluation. Patients with suspected gastroparesis underwent a scintigraphic gastric emptying test. Definitive diagnoses were made at discharge.

Results: Patients with higher levels of incongruence differed in various sociodemographic (age, educational level, work activity and having children) and psychopathological (all SCL-90-R subscales except anxiety and hostility) characteristics. Using general lineal models, incongruence was found to be the variable with stronger relations with psychopathology even when controlling for diagnosis. Interactions were found between incongruence and diagnosis reflecting a pattern in which patients with functional disorders whose subjective evaluation of functioning is not congruent with that of the clinician, have higher levels of psychopathology than patients with motor disorders.

Conclusions: Incongruence between clinician and self-reported functionality seems to be related to higher levels of psychopathology in patients with functional disorders. These findings underscore the need for routine psychosocial assessment among these patients. Gastroenterologists could use the concept of incongruence and its clinical implications, as a screening tool for psychopathology, facilitating consultation-liaison processes.
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http://dx.doi.org/10.1016/j.jpsychores.2017.06.005DOI Listing
August 2017

Correction of Abdominal Distention by Biofeedback-Guided Control of Abdominothoracic Muscular Activity in a Randomized, Placebo-Controlled Trial.

Clin Gastroenterol Hepatol 2017 Dec 11;15(12):1922-1929. Epub 2017 Jul 11.

Digestive System Research Unit, University Hospital Vall d'Hebron; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd); Department de Medicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain. Electronic address:

Background & Aims: Abdominal distention is produced by abnormal somatic postural tone. We developed an original biofeedback technique based on electromyography-guided control of abdominothoracic muscular activity. We performed a randomized, placebo-controlled study to demonstrate the superiority of biofeedback to placebo for the treatment of abdominal distention.

Methods: At a referral center in Spain, we enrolled consecutive patients with visible abdominal distention who fulfilled the Rome III criteria for functional intestinal disorders (47 women, 1 man; 21-74 years old); 2 patients assigned to the placebo group withdrew and 2 patients assigned to biofeedback were not valid for analysis. Abdominothoracic muscle activity was recorded by electromyography. The patients in the biofeedback group were shown the signal and instructed to control muscle activity, whereas patients in the placebo received no instructions and were given oral simethicone. Each patient underwent 3 sessions over a 10-day period. The primary outcomes were subjective sensation of abdominal distention, measured by graphic rating scales for 10 consecutive days before and after the intervention.

Results: Patients in the biofeedback group effectively learned to reduce intercostal activity (by a mean 45% ± 3%), but not patients in the placebo group (reduced by a mean 5% ± 2%; P < .001). Patients in the biofeedback group learned to increase anterior wall muscle activity (by a mean 101% ± 10%), but not in the placebo group (decreased by a mean 4% ± 2%; P < .001). Biofeedback resulted in a 56% ± 1% reduction of abdominal distention (from a mean score of 4.6 ± 0.2 to 2.0 ± 0.2), whereas patients in the placebo group had a reduction of only 13% ± 8% (from a mean score of 4.7 ± 0.1 to 4.1 ± 0.4) (P < .001).

Conclusions: In a randomized trial of patients with a functional intestinal disorder, we found that abdominal distention can be effectively corrected by biofeedback-guided control of abdominothoracic muscular activity, compared with placebo. ClincialTrials.gov no: NCT01205100.
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http://dx.doi.org/10.1016/j.cgh.2017.06.052DOI Listing
December 2017

Bloating and Abdominal Distension: Old Misconceptions and Current Knowledge.

Am J Gastroenterol 2017 Aug 16;112(8):1221-1231. Epub 2017 May 16.

Digestive System Research Unit, University Hospital Vall d'Hebron; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Spain.

Bloating, as a symptom and abdominal distension, as a sign, are both common functional-type complaints and challenging to manage effectively. Individual patients may weight differently the impact of bloating and distension on their well-being. Complaints may range from chronic highly distressing pain to simply annoying and unfashionable protrusion of the abdomen. To avoid mishaps, organic bloating, and distension should always be considered first and appropriated assessed. Functional bloating and distension often present in association with other manifestations of irritable bowel syndrome or functional dyspepsia and in that context patients tend to regard them as most troublesome. A mechanism-based management bloating and distension should be ideal but elucidating key operational mechanisms in individual patients is not always feasible. Some clues may be gathered through a detailed dietary history, by assessing bowel movement frequency and stool consistency and special imaging technique to measure abdominal shape during episodes of distension. In severe, protracted cases it may be appropriate to refer the patient to a specialized center where motility, visceral sensitivity, and abdominal muscle activity in response to intraluminal stimuli may be measured. Therapeutic resources focussed upon presumed or demonstrated pathogenetic mechanism include dietary modification, microbiome modulation, promoting gas evacuation, attenuating visceral perception, and controlling abdominal wall muscle activity via biofeedback.
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http://dx.doi.org/10.1038/ajg.2017.129DOI Listing
August 2017

Effect of prucalopride on intestinal gas tolerance in patients with functional bowel disorders and constipation.

J Gastroenterol Hepatol 2017 Aug;32(8):1457-1462

Digestive System Research Unit, University Hospital Vall d'Hebron, Barcelona, Spain.

Background And Aim: Patients with functional bowel disorders develop gas retention and symptoms in response to intestinal gas loads that are well tolerated by healthy subjects. Stimulation of 5HT-4 receptors in the gut has both prokinetic and antinociceptive effects. The aim of this study is to determine the effect of prucalopride, a highly selective 5HT-4 agonist, on gas transit and tolerance in women with functional bowel disorders complaining of constipation.

Methods: Twenty-four women with functional bowel disorders complaining of constipation were included in the study. Patients were studied twice on separate days in a cross-over design. On each study day, an intestinal gas challenge test was performed. During the five previous days, prucalopride (2 mg/day) or placebo was administered. Abdominal symptoms, stool frequency, and stool consistency were recorded during the treatment period on daily questionnaires.

Results: During the gas challenge test, prucalopride did not decrease the volume of gas retained in the subset of patients who had significant gas retention (≥ 200 mL) while on placebo. However, in those patients who had increased symptoms during the gas test (≥ 3 on a 0 to 6 scale) when on placebo, prucalopride did significantly reduce the perception of symptoms (2.3 ± 0.5 mean score vs 3.5 ± 0.3 on placebo; P = 0.045). During the treatment period with prucalopride, patients exhibited an increase in the total number of bowel movements and decreased stool consistency compared with placebo.

Conclusion: Prucalopride reduces abdominal symptoms without modifying gas retention when patients with functional bowel disorders are challenged with the gas transit and tolerance test. European Clinical Trials Database (EudraCT2011-006354-86).
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http://dx.doi.org/10.1111/jgh.13733DOI Listing
August 2017

High-resolution manometry in patients with idiopathic inflammatory myopathy: Elevated prevalence of esophageal involvement and differences according to autoantibody status and clinical subset.

Muscle Nerve 2017 09 4;56(3):386-392. Epub 2017 Apr 4.

Autoimmune Systemic Diseases Unit, Department of Internal Medicine, Vall d'Hebron University Hospital, Passeig de la Vall d'Hebron, 119-129, 08035, Barcelona, Spain.

Introduction: In this study we assessed high-resolution manometry (HRM) findings in patients with dermatomyositis and polymyositis.

Methods: From 2008 to 2015, we performed a cross-sectional study of myositis patients. A survey of esophageal symptoms and HRM data were analyzed and compared among different clinical and serologic groups.

Results: Twenty-four (45%) of the 53 patients included in the study had manometric involvement that was not correlated with any esophageal symptom (P = 0.8). Failed waves (34% vs. 0%, P = 0.004) and decreased upper esophageal sphincter pressure (50 vs. 70 mm Hg, P = 0.03) were more common in polymyositis than in dermatomyositis patients. Jackhammer esophagus was more common in anti-TIF1-γ patients (30% vs. 9%, P = 0.04), and lower esophageal sphincter involvement (47% vs. 25%, P = 0.03) was more prevalent in patients with the antisynthetase syndrome.

Conclusions: Esophageal involvement is common in myositis patients, but it correlates poorly with esophageal symptoms. Specific clinical and serologic groups have different manometric features. Muscle Nerve 56: 386-392, 2017.
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http://dx.doi.org/10.1002/mus.25507DOI Listing
September 2017

Effect of Chicory-derived Inulin on Abdominal Sensations and Bowel Motor Function.

J Clin Gastroenterol 2017 Aug;51(7):619-625

*Digestive System Research Unit, University Hospital Vall d'Hebron, Barcelona †Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd) (Virtual Center for Biomedical Research Hepatic and Digestive Diseases), Madrid ‡Department de Medicina, Universitat Autònoma de Barcelona (Department of Medicine, Autonomous University of Barcelona), Bellaterra (Cerdanyola del Vallès), Spain §BENEO-Institute, Obrigheim, Germany.

Goal: To determine the effect of a prebiotic chicory-derived inulin-type fructan on the tolerance of intestinal gas.

Background: Subjects with gas-related complaints exhibit impaired handling of intestinal gas loads and we hypothesized that inulin would have a beneficial effect.

Study: Placebo-controlled, parallel, randomized, double-blind trial. Subjects with abdominal symptoms and reduced tolerance of intestinal gas (selected by a pretest) received either inulin (8 g/d, n=18) or maltodextrin as a placebo (8 g/d, n=18) for 4 weeks. A gas challenge test (4 h jejunal gas infusion at 12 mL/min while measuring abdominal symptoms and gas retention for 3 h) was performed before and at the end of the intervention phase. Gastrointestinal symptoms and bowel habits (using daily questionnaires for 1 wk) and fecal bifidobacteria counts were measured before and at the end of the intervention.

Results: Inulin decreased gas retention during the gas challenge test (by 22%; P=0.035 vs. baseline), while the placebo did not, but the intergroup difference was not statistically significant (P=0.343). Inulin and placebo reduced the perception of abdominal sensations in the gas challenge test to a similar extent (by 52% and 43%, respectively). Participants reported moderate gastrointestinal symptoms and normal bowel habits during baseline examination, and these findings remained unchanged in both groups during the intervention. Inulin led to a higher relative abundance of bifidobacteria counts (P=0.01 vs. placebo).

Conclusions: A daily dose of inulin that promotes bifidobacteria growth and may improve gut function, is well tolerated by subjects with gastrointestinal complaints.
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http://dx.doi.org/10.1097/MCG.0000000000000723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499961PMC
August 2017

Incongruence between Clinicians' Assessment and Self-Reported Functioning Is Related to Psychopathology among Patients Diagnosed with Gastrointestinal Disorders.

Psychother Psychosom 2016;85(4):244-5. Epub 2016 May 27.

Consultation-Liaison Psychiatry Unit, Department of Psychiatry, University Hospital Vall d'Hebron, CIBERSAM, Barcelona, Spain.

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http://dx.doi.org/10.1159/000443899DOI Listing
March 2017
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