Editorial: Human Intestinal Permeability, Mucosal Inflammation and Diet

Intestinal permeability; Microbiota; NutritionPermeabilidad intestinal; Microbiota; NutriciónPermeabilitat intestinal; Microbiota; NutricióThis work was supported in part by Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Economía y Competitividad: PI17/0190 (JS), CIBERehd CB06/04/0021 (JS), the DISCOVERIE project, GA no: 848228 (JS, GB). This project has received funding from the European Union's 2020 research and innovation programme under grant agreement No. 848228

Efficacy and Safety of a Novel Therapeutic of Natural Origin (NTN) in Adult Patients with Lactose Intolerance: A Multicenter, Randomized, Crossover, Double-Blind, Placebo-Controlled Study

Food intolerance; Intestinal barrier; Natural therapeuticIntolerància alimentària; Barrera intestinal; Terapèutica naturalIntolerancia alimentaria; Barrera intestinal; Terapéutica naturalBackground: Film-forming substances, such as natural polysaccharides (NP) and pea proteins (PP), act as a protective barrier for treating various gastrointestinal conditions. We assessed the efficacy and safety of a novel therapeutic of natural origin (NTN) containing NP and PP for symptomatic treatment of lactose intolerance. Methods: In this multicenter, randomized, double-blind, parallel-group study, patients with lactose intolerance received NTN (n = 30) or placebo (n = 30) for 7 days, then the alternate treatment for 7 days. Patients rated their gastrointestinal symptoms using a 7-point Likert scale. The lactose hydrogen breath test was used to assess exhaled hydrogen. Results: NTN as primary or crossover treatment significantly improved patient-reported symptoms of bloating, distension, and abdominal pain. Abdominal pain also improved under primary treatment with placebo. Primary treatment with NTN, but not placebo, normalized mean exhaled hydrogen levels. In the group allocated initially to placebo, crossover to NTN attenuated the increase in hydrogen production. No treatment-related adverse effects were reported in either group. Conclusions: Subjective improvements in bloating, distension, and abdominal pain with NTN were supported by objective evidence of hydrogen production normalization. NTN appears to be a useful alternative to lactose avoidance or enzyme replacement in patients with lactose intolerance.The study was sponsored by Novinthetical Pharma SA, Lugano, Switzerland

Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study

DGBI; IBS; EpidemiologyDGBI; IBS; EpidemiologiaDGBI; IBS; EpidemiologíaBackground & Aims Although functional gastrointestinal disorders (FGIDs), now called disorders of gut-brain interaction, have major economic effects on health care systems and adversely affect quality of life, little is known about their global prevalence and distribution. We investigated the prevalence of and factors associated with 22 FGIDs, in 33 countries on 6 continents. Methods Data were collected via the Internet in 24 countries, personal interviews in 7 countries, and both in 2 countries, using the Rome IV diagnostic questionnaire, Rome III irritable bowel syndrome questions, and 80 items to identify variables associated with FGIDs. Data collection methods differed for Internet and household groups, so data analyses were conducted and reported separately. Results Among the 73,076 adult respondents (49.5% women), diagnostic criteria were met for at least 1 FGID by 40.3% persons who completed the Internet surveys (95% confidence interval [CI], 39.9–40.7) and 20.7% of persons who completed the household surveys (95% CI, 20.2–21.3). FGIDs were more prevalent among women than men, based on responses to the Internet survey (odds ratio, 1.7; 95% CI, 1.6–1.7) and household survey (odds ratio, 1.3; 95% CI, 1.3–1.4). FGIDs were associated with lower quality of life and more frequent doctor visits. Proportions of subjects with irritable bowel syndrome were lower when the Rome IV criteria were used, compared with the Rome III criteria, in the Internet survey (4.1% vs 10.1%) and household survey (1.5% vs 3.5%). Conclusions In a large-scale multinational study, we found that more than 40% of persons worldwide have FGIDs, which affect quality of life and health care use. Although the absolute prevalence was higher among Internet respondents, similar trends and relative distributions were found in people who completed Internet vs personal interviews.The study was funded, in part, by research grants from Ironwood, Shire, Allergan, and Takeda. The study in Malaysia was funded by the Fundamental Research Grant Scheme (FRGS) of the Ministry of Education of Malaysia (Reference: 203.PPSP.6171192). The study in Israel was funded by Takeda-Israel. The study in Romania was funded by the Romanian Society of Neurogastroenterology. None of the funders was involved in the planning, design, implementation, statistical analyses or any other aspect of the study including preparation of the paper or knowledge of its contents

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome

5-HT; IBS; Transportador de serotonina5-HT; IBS; Transportador de serotonina5-HT; IBS; Serotonin transporterIrritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis

The Intestinal Gas Questionnaire (IGQ): Psychometric validation of a new instrument for measuring gas-related symptoms and their impact on daily life among general population and irritable bowel syndrome

Gas-related symptoms; Patient-reported outcomes; Quality of lifeSíntomas relacionados con los gases; Resultados informados por el paciente; Calidad de vidaSímptomes relacionats amb els gasos; Resultats informats pel pacient; Qualitat de vidaBackground Gas-related symptoms (GRS) are common in the general population (GPop) and among patients with disorders of gut-brain interactions but there is no patient-reported outcome evaluating these symptoms and their impact on daily life. We have previously developed a 43-item intestinal gas questionnaire (IGQ). The aim of the present study is to perform a psychometric validation of this instrument. Methods Participants (119 from the GPop and 186 irritable bowel syndrome (IBS) patients) were recruited from 3 countries (UK, Spain, France). IBS patients fulfilled ROME IV criteria with an IBS severity score between 150 and 300. Participants completed the IGQ, the functional Digestive Disorders Quality of Life (FDDQL), and the EQ-5D. A subgroup (n = 90) repeated the IGQ completion after 7 days on paper or electronically. Results From the original IGQ questionnaire, 26 items were deleted because of poor performance. Confirmatory factorial analysis on the remaining 17 items (7 symptom and 10 impact items) yielded a 6-factor structure accounting for 67% of the variance for bloating (6 items), flatulence (3), belching (2), bad breath (2), stomach rumbling (2), and difficult gas evacuation (2). Global score (0-100) was worse among IBS vs GPop (40 ± 15 vs 33 ± 17; p = 0.0016). At the second visit, the intraclass correlation coefficient of IGQ scores was between 0.71 and 0.86 (n = 67) for test-retest reliability and 0.61-0.87 (n = 64) for equivalence between electronic and paper versions of IGQ. Conclusion The IGQ available in paper and electronic versions in 3 languages is a robust instrument for capturing and measuring GRS and their impact on daily life.This Investigator Sponsored Study has been funded by Danone Research. Danone did not interfere with the analysis and interpretation of data. The work was supported in part by the Spanish Ministry of Economy and Competitiveness (Dirección General de Investigación Científica y Técnica, SAF 2016-76648-R). Ciberehd is funded by the Instituto de Salud Carlos II

Eosinophils in the Gastrointestinal Tract: Key Contributors to Neuro-Immune Crosstalk and Potential Implications in Disorders of Brain-Gut Interaction

Disorders of brain-gut interaction; Intestinal eosinophils; Neuro-immune interactionTrastorns de la interacció cervell-intestí; Eosinòfils intestinals; Interacció neuroimmuneTrastornos de la interacción cerebro-intestino; Eosinófilos intestinales; Interacción neuroinmuneEosinophils are innate immune granulocytes actively involved in defensive responses and in local and systemic inflammatory processes. Beyond these effector roles, eosinophils are fundamental to maintaining homeostasis in the tissues they reside. Gastrointestinal eosinophils modulate barrier function and mucosal immunity and promote tissue development through their direct communication with almost every cellular component. This is possible thanks to the variety of receptors they express and the bioactive molecules they store and release, including cytotoxic proteins, cytokines, growth factors, and neuropeptides and neurotrophines. A growing body of evidence points to the eosinophil as a key neuro-immune player in the regulation of gastrointestinal function, with potential implications in pathophysiological processes. Eosinophil–neuron interactions are facilitated by chemotaxis and adhesion molecules, and the mediators released may have excitatory or inhibitory effects on each cell type, with physiological consequences dependent on the type of innervation involved. Of special interest are the disorders of the brain–gut interaction (DBGIs), mainly functional dyspepsia (FD) and irritable bowel syndrome (IBS), in which mucosal eosinophilia and eosinophil activation have been identified. In this review, we summarize the main roles of gastrointestinal eosinophils in supporting gut homeostasis and the evidence available on eosinophil–neuron interactions to bring new insights that support the fundamental role of this neuro-immune crosstalk in maintaining gut health and contributing to the pathophysiology of DBGIs.This study was funded in part by the Fondo Europeo de Desarrollo Regional (FEDER), the Fondo de Investigación Sanitaria, the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), the Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, and the Ministerio de Economía y Competitividad: FI12/00254 (E.S-R.), CD15/00010 (B.K.R.-J.), FI20/00256 (M.A-B.), PI19/01643 (B.L.), PI17/0190 (J.S.), CP18/00116 (C.M), CPII16/00031 and PI19/01643 (M.V.), CIBEREHD CB06/04/0021 (J.S., R.F., M.V.)

Blastocystis sp. Carriage and Irritable Bowel Syndrome: Is the Association Already Established?

Blastocystis sp.; Irritable bowel syndrome; PathogenesisBlastocystis sp.; Síndrome de l'intestí irritable; PatogènesiBlastocystis sp.; Síndrome del intestino irritable; PatogénesisBackground: The aim of the present study is to describe the occurrence of Blastocystis sp. detection among asymptomatic subjects and patients with irritable bowel syndrome in order to evaluate the potential association between irritable bowel syndrome and the parasitic infection. Methods: Cross-sectional study where adult patients with irritable bowel syndrome diagnosed according to Rome IV criteria were included. A control group was formed by asymptomatic subjects older than 18 years. Exclusion criteria were: immunosuppressive condition or having received any drug with demonstrated activity against Blastocystis sp. within the last 6 months before study inclusion. Epidemiological and clinical information was collected from all included participants. Two stool samples were obtained from all participants: one sample for microscopic examination and one sample for Blastocystis sp. PCR detection. Blastocystis sp. infection was defined by the positivity of any of the diagnostic techniques. Results: Seventy-two participants were included (36 asymptomatic subjects and 36 patients with irritable bowel syndrome). Thirty-five (48.6%) were men, and median age of participants was 34 (IQR 29–49) years. The overall rate of Blastocystis sp. carriage was 27.8% (20/72). The prevalence assessed through microscopic examination was 22.2% (16/72), while the prevalence measured by PCR was 15.3% (11/72). When comparing the presence of Blastocystis sp. between asymptomatic subjects and IBS patients, we did not find any statistically significant difference (36.1% vs. 19.4% respectively, p = 0.114). Conclusions: regarding the occurrence of Blastocystis sp., no differences were found between asymptomatic participants and patients with irritable bowel disease irrespective of the diagnostic technique performed.This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors

Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations

Intestinal barrier dysfunction; Intestinal glycocalyx; Mucosal nerve fibresDisfunción de la barrera intestinal; Glicocálix intestinal; Fibras nerviosas de la mucosaDisfunció de la barrera intestinal; Glicocàlix intestinal; Fibres nervioses de la mucosaIrritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.This study was funded in part by Fondo Europeo de Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Economía y Competitividad: CP18/00116 (C.M.), PI19/01643 (B.L.); PI17/01443 (D.G.); PI15/00301 (C.A.-C.), PI17/0190 (J.S.), PI19/01643 & CPII16/00031, (M.V.); CIBEREHD CB06/04/0021 (F.A., C.A.-C., J.S., M.V.); Ministerio de Educación, Dirección General de Investigación: SAF 2016-76648-R (F.A.); Agència de Gestió d’Ajuts Universitaris i de Recerca, de la Generalitat de Catalunya: 2014 SGR 1285 (F.A.); Vall d’Hebron Institut de Recerca, Programa de becas predoctorales Amics de Vall d’Hebron: PRED-VHIR-2016-34 (C.P.-C.), PRED-VHIR-2014-018 (M.F.), the Swedish Research Council dnr 2019-00653 (J.-P.G.M.), and the European Union’s Horizon research and innovation programme 2020, grant no. 848228 (E.E., A.R.-U., B.L., C.A.-C., J.S.)

Effect of Paraffin and Silica Matrix Phase Change Materials on Properties of Portland Cement Mortars

In the search for methods to incorporate Phase Change Materials (PCM) into Portland cement mortar mixtures, PCM based on paraffins adhered to a silica-based matrix appear as a suitable option. However, paraffin particles have been observed to escape from the silica matrix when water is added. There are only limited data on how the use of such PCM affects the behaviour of mortars. To evaluate the effect of this PCM addition, Portland mortar mixtures were elaborated with 5%, 10% and 15% of PCM content, and using CEM 42.5 I R and CEM I 52.5 R cement types. Physical properties such as density, open porosity, air content and water absorption were analysed for fresh and dry samples. The results obtained show that the PCM-added mixtures require greater water and cement amounts than the standard mortar mixtures to achieve similar compressive strengths. Compared to non-PCM mixtures the PCM-added mortars present a density lowering of 37% for fresh mixtures and near 45% for dry state forms. A maximum compressive strength of 15.9 MPa was reached for 15% PCM mixtures, while values beyond 40 MPa were achieved for 5% PCM mixtures. Thus, the proposed study contributes to broad the available knowledge of PCM cement mortar mixtures behaviour and their mix design

Experimental assessment of energy storage in microencapsulated paraffin PCM Cement mortars

Thermal Energy Storage (TES) methods have gained significant importance in reducing the energy demand of buildings. Among various TES methods, the use of Phase Change Materials (PCM) has emerged as a promising approach to store energy in latent form and enhance the thermal capacity of buildings, thereby improving thermal comfort. This study aims to evaluate the sensible and latent energy accumulation in cement mortars by incorporating microencapsulated phase change materials (10–20% by weight) as a substitute for fine aggregates. The experimental investigation involved density measurements, differential scanning calorimetry (DSC) analysis, and accumulated energy tests. The results indicate that the PCM content increases, the heating and cooling rates are lower, and the temperature difference between the ambient exposed face and the not-exposed face of tested slabs increases. Additionally, the latent heat energy contribution increases when the material is exposed to lower temperature gradients, coinciding with the temperature range at which phase change occurs. The total energy accumulated in mortars with 10% and 20% PCM content increases in 238–330%, respectively, for a 5 ºC temperature gradient. However, when a 15 ºC temperature gradient is used, the accumulated energy increases at 70% and 88%, respectively