Publications by authors named "Lucas Wauters"

50 Publications

Enterohormone therapy for short bowel syndrome.

Curr Opin Endocrinol Diabetes Obes 2022 Jan 14. Epub 2022 Jan 14.

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (ChroMetA), University of Leuven, Herestraat 49, 3000 Leuven, Belgium Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.

Purpose Of This Review: Short bowel syndrome (SBS) patients are at risk to develop intestinal failure when the decreased absorption of macronutrients, water, and electrolytes necessitates parenteral support for survival. The adverse effects of SBS and parenteral support negatively affect the quality of life (QoL) of SBS-intestinal failure patients. However, spontaneous intestinal adaptation along with disease-modifying therapies allow reducing parenteral support, thereby improving QoL.

Recent Findings: During the first years following extensive surgery, spontaneous structural and functional intestinal changes take place which stimulate a more efficient nutrient and fluid absorption in the remaining bowel. Given their potential role in the ileal braking mechanism, enterohormones, such as glucagon-like peptide (GLP)-2, GLP-1, and peptide YY (PYY), promote an accelerated adaptation or hyperadaptation. While the exact role of GLP-1 and PYY in SBS is still being explored, GLP-2 analogs have clearly shown to be effective in improving outcome in SBS.

Summary: Whereas spontaneous intestinal adaptation improves the nutritional status of SBS patients to a certain extent, GLP-2 analogs can further decrease parenteral support needs through hyperadaptation. There are, however, other promising candidates on the horizon that - alone or in combination - could possibly establish additional disease-modifying effects.
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http://dx.doi.org/10.1097/MED.0000000000000710DOI Listing
January 2022

Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia.

Int J Mol Sci 2021 Dec 19;22(24). Epub 2021 Dec 19.

VIB Center for Microbiology, 3000 Leuven, Belgium.

Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.
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http://dx.doi.org/10.3390/ijms222413609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708077PMC
December 2021

Duodenal Barrier and Inflammation in Dyspepsia: God is in the Details.

Clin Gastroenterol Hepatol 2021 Nov 13. Epub 2021 Nov 13.

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1016/j.cgh.2021.11.005DOI Listing
November 2021

Spore-forming probiotics for functional dyspepsia - Authors' reply.

Lancet Gastroenterol Hepatol 2021 12;6(12):983-984

Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium; Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium. Electronic address:

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http://dx.doi.org/10.1016/S2468-1253(21)00381-2DOI Listing
December 2021

Role of Eosinophils in Intestinal Inflammation and Fibrosis in Inflammatory Bowel Disease: An Overlooked Villain?

Front Immunol 2021 19;12:754413. Epub 2021 Oct 19.

Department of Chronic Diseases and Metabolism, Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium.

Eosinophils are leukocytes which reside in the gastrointestinal tract under homeostatic conditions, except for the esophagus which is normally devoid of eosinophils. Research on eosinophils has primarily focused on anti-helminth responses and type 2 immune disorders. In contrast, the search for a role of eosinophils in chronic intestinal inflammation and fibrosis has been limited. With a shift in research focus from adaptive to innate immunity and the fact that the eosinophilic granules are filled with inflammatory mediators, eosinophils are becoming a point of interest in inflammatory bowel diseases. In the current review we summarize eosinophil characteristics and recruitment as well as the current knowledge on presence, inflammatory and pro-fibrotic functions of eosinophils in inflammatory bowel disease and other chronic inflammatory conditions, and we identify research gaps which should be covered in the future.
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http://dx.doi.org/10.3389/fimmu.2021.754413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560962PMC
October 2021

Exotic Pet Trade as a Cause of Biological Invasions: The Case of Tree Squirrels of the Genus .

Biology (Basel) 2021 Oct 15;10(10). Epub 2021 Oct 15.

Haub School of Environment and Natural Resources, University of Wyoming, 1000 E. University Ave, Laramie, WY 82071, USA.

The trade of non-native pets, especially of non-domesticated and exotic animals, and their subsequent release and establishment of populations is one of the major pathways of introduction for invasive alien reptiles, amphibia, birds and mammals. Here, we use a group of arboreal mammals, tree squirrels of the genus , as a well-documented case study, reviewing the pathways of introduction, the current areas of non-native distribution, the rate of establishment success and the challenge and legal importance of species identification. We further illustrate the importance of early detection and effective monitoring methods and plans. Next, we document how they interfere with native species, their risk of acting as vectors for emerging infectious diseases and their potential role in maintaining parasitic infections that can affect human health. We conclude by reviewing the current management, or the lack of it, and highlight the diverse biological, social, political and economic reasons that make control/eradication of these charismatic species difficult or even impractical in most countries. However, reviewing the only two successful eradications of the IAS, we highlight the need to acknowledge the public opinion and the importance of communication, transparency and the engagement of a diversity of stakeholders to create a consensus about the actions to undertake.
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http://dx.doi.org/10.3390/biology10101046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533491PMC
October 2021

Specific contributions of segmental transit times to gut microbiota composition.

Gut 2021 Oct 12. Epub 2021 Oct 12.

Department of Chronic Diseases and Metabolism, Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium

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http://dx.doi.org/10.1136/gutjnl-2021-325916DOI Listing
October 2021

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

Duodenum at a crossroads: Key integrator of overlapping and psychological symptoms in functional dyspepsia?

Neurogastroenterol Motil 2021 10 24;33(10):e14262. Epub 2021 Sep 24.

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

The study of the interaction between gastrointestinal (GI) function and psychological features is a complex and developing field. The bidirectional communication between the gut and the brain or gut-brain axis is considered as a pivotal player in the pathogenesis of the highly prevalent functional GI disorders, including irritable bowel syndrome and functional dyspepsia (FD), which have been redefined as disorders of gut-brain interaction. However, the mechanisms through which changes in the gut alter brain functioning, feelings, and behavior remain unclear. Based on the presence of duodenal pathology in adult FD patients, Ronkainen et al. provide the first prospective evidence for duodenal eosinophils potentially driving anxiety. Also in this edition, associations between gastroduodenal pathology and rumination syndrome, which may coexist with FD, have now been confirmed in children by Friesen et al. Together these findings confirm not only the potential role of duodenal alterations in determining overlapping upper GI but also psychological symptoms, which result from bidirectional and complex interactions. In this review, we provide an overview of the recent advances in this field and highlight the novel contributions of the original studies of Ronkainen et al. and Friesen et al. to this topic.
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http://dx.doi.org/10.1111/nmo.14262DOI Listing
October 2021

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

Neurogastroenterol Motil 2021 08;33(8):e14237

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

Background: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis.

Methods: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements.

Results: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis.
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http://dx.doi.org/10.1111/nmo.14237DOI Listing
August 2021

Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial.

Lancet Gastroenterol Hepatol 2021 10 3;6(10):784-792. Epub 2021 Aug 3.

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; Translational Research in Gastrointestinal Disorders, KU Leuven, Leuven, Belgium. Electronic address:

Background: Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors.

Methods: In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium), adult patients (≥18 years) with functional dyspepsia (as defined by Rome IV criteria, on proton-pump inhibitors or off proton-pump inhibitors) were randomly assigned (1:1) via computer-generated blocked lists, stratified by proton-pump inhibitor status, to receive 8 weeks of treatment with probiotics (Bacillus coagulans MY01 and Bacillus subtilis MY02, 2·5 × 10 colony-forming units per capsule) or placebo consumed twice per day, followed by an open-label extension phase of 8 weeks. Individuals with a history of abdominal surgery, diabetes, coeliac or inflammatory bowel disease, active psychiatric conditions, and use of immunosuppressant drugs, antibiotics, or probiotics in the past 3 months were excluded. All patients and on-site study personnel were masked to treatment allocation in the first 8 weeks. Symptoms, immune activation, and faecal microbiota were assessed and recorded. The primary endpoint was a decrease of at least 0·7 in the postprandial distress syndrome (PDS) score of the Leuven Postprandial Distress Scale in patients with a baseline PDS score of 1 or greater (at least mild symptoms), assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04030780.

Findings: Between June 3, 2019, and March 11, 2020, of 93 individuals assessed for eligibility, we included 68 patients with functional dyspepsia (51 [75%] women, mean age 40·1 years [SD 14·4], 34 [50%] on proton-pump inhibitors). We randomly assigned 32 participants to probiotics and 36 to placebo. The proportion of clinical responders was higher with probiotics (12 [48%] of 25) than placebo (six [20%] of 30; relative risk 1·95 [95% CI 1·07-4·11]; p=0·028). The number of patients with adverse events was similar with probiotics (five [16%] of 32) and placebo (12 [33%] of 36). Two serious adverse events occurring during the open-label phase (appendicitis and syncope in two separate patients) were assessed as unlikely to be related to the study product.

Interpretation: In this exploratory study, B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of functional dyspepsia. Participants had potentially beneficial immune and microbial changes, which could provide insights into possible underlying mechanisms as future predictors or treatment targets.

Funding: MY HEALTH.
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http://dx.doi.org/10.1016/S2468-1253(21)00226-0DOI Listing
October 2021

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

United European Gastroenterol J 2021 04;9(3):287-306

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

Background: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis.

Methods: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements.

Results: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause.

Conclusions And Inferences: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis.
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http://dx.doi.org/10.1002/ueg2.12060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259275PMC
April 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

Camera Trapping to Assess Status and Composition of Mammal Communities in a Biodiversity Hotspot in Myanmar.

Animals (Basel) 2021 Mar 19;11(3). Epub 2021 Mar 19.

Environment Analysis and Management Unit-Guido Tosi Research Group-Department of Theoretical and Applied Sciences, University of Insubria, Via J. H. Dunant, 3, 21100 Varese, Italy.

Tropical forests comprise a critically impacted habitat, and it is known that altered forests host a lower diversity of mammal communities. In this study, we investigated the mammal communities of two areas in Myanmar with similar environmental conditions but with great differences in habitat degradation and human disturbance. The main goal was to understand the status and composition of these communities in an understudied area like Myanmar at a broad scale. Using camera trap data from a three-year-long campaign and hierarchical occupancy models with a Bayesian formulation, we evaluated the biodiversity level (species richness) and different ecosystem functions (diet and body mass), as well as the occupancy values of single species as a proxy for population density. We found a lower mammal diversity in the disturbed area, with a significantly lower number of carnivores and herbivores species. Interestingly, the area did not show alteration in its functional composition. Almost all the specific roles in the community were present except for apex predators, thus suggesting that the effects of human disturbance are mainly effecting the communities highest levels. Furthermore, two species showed significantly lower occupancies in the disturbed area during all the monitoring campaigns: one with a strong pressure for bushmeat consumption and a vulnerable carnivore threatened by illegal wildlife trade.
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http://dx.doi.org/10.3390/ani11030880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003726PMC
March 2021

Personality traits, sex and food abundance shape space use in an arboreal mammal.

Oecologia 2021 May 1;196(1):65-76. Epub 2021 Apr 1.

Department of Veterinary Medicine, Università degli Studi di Milano, Milan, Italy.

Animal space use is affected by spatio-temporal variation in food availability and/or population density and varies among individuals. This inter-individual variation in spacing behaviour can be further influenced by sex, body condition, social dominance, and by the animal's personality. We used capture-mark-recapture and radio-tracking to examine the relationship between space use and personality in Eurasian red squirrels (Sciurus vulgaris) in three conifer forests in the Italian Alps. We further explored to what extent this was influenced by changes in food abundance and/or population density. Measures of an individual's trappability and trap diversity had high repeatability and were used in a Principal Component Analysis to obtain a single personality score representing a boldness-exploration tendency. Males increased home-range size with low food abundance and low female density, independent of their personality. However, bolder males used larger core-areas that overlapped less with other males than shy ones, suggesting different resource (food, partners) utilization strategies among personality types. For females, space use-personality relationships varied with food abundance, and bolder females used larger home ranges than shy ones at low female density, but the trend was opposite at high female density. Females' intrasexual core-area overlap was negatively related to body mass, with no effect of personality. We conclude that relationships between personality traits and space use in free-ranging squirrels varied with sex, and were further influenced by spatio-temporal fluctuations in food availability. Moreover, different personality types (bold-explorative vs. shy) seemed to adopt different space-use strategies to increase access to food and/or partners.
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http://dx.doi.org/10.1007/s00442-021-04901-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139925PMC
May 2021

Health Literacy and Quality of Life in Young Adults From The Belgian Crohn's Disease Registry Compared to Type 1 Diabetes Mellitus.

Front Pediatr 2021 5;9:624416. Epub 2021 Feb 5.

Pediatric Gastroenterology, UZ Brussels, Jette, Belgium.

The management of chronic inflammatory bowel diseases in youth is challenging. We aimed to determine health literacy (HL), quality of life (QoL) and clinical outcomes in young adults from the BELgian CROhn's disease registry (BELCRO) in comparison to type 1 diabetes mellitus (DM) as a control. In this prospective and observational study, young adults with Crohn's disease (CD) diagnosed < 18 years and with > 5 years disease duration and a comparable group of patients with DM completed validated HL, QoL and work productivity and activity impairment questionnaires (HLS-EU-Q16, EQ-5D-5L and WPAI). HL was scored as sufficient (13-16), problematic (9-12) or inadequate (0-8). QoL was dichotomized into "no problems" (EQ-5D level 1) or "problems" (EQ-5D levels 2 to 5). Non-parametric (Mann-Whitney ) analyses and Spearman correlations were performed. A total of 52 CD (median [IQR] age of 25.0 [23.8-27.0], 64% male) and 50 DM (age 20.0 [19.0-22.0], 50% male) patients were included. HL was 14.0 [11.0-16.0] for CD and 14.0 [11.3-14.8] for DM ( = 0.6) with similar proportions of sufficient (60 vs. 68%, = 0.4), problematic (34 vs. 26%, = 0.3) and inadequate HL (both 6%, = 1). Although QoL was comparable for CD and DM (77.0 [68.8-82.0] vs. 75.0 [65.0-80.0] %, =0.4), CD had a trend for higher pain/discomfort (50 vs. 32%, = 0.06). HL and QoL correlated in CD ( = 0.6, < 0.001) and DM patients ( = 0.6, < 0.001). Fewer CD patients with recent hospitalization/surgery had sufficient HL (31 vs. 69%, = 0.01) and had lower QoL (70.0 [60.0-77.0] vs. 80.0 [70.0-85.0], = 0.04) compared to those without. Selected young Belgian adults suffering from CD for >5 years have similar and sufficient HL compared to DM patients. However, CD patients requiring hospitalization/surgery have lower HL, which indicates the need for targeted educational programs.
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http://dx.doi.org/10.3389/fped.2021.624416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892785PMC
February 2021

Proton Pump Inhibitors Reduce Duodenal Eosinophilia, Mast Cells, and Permeability in Patients With Functional Dyspepsia.

Gastroenterology 2021 04 18;160(5):1521-1531.e9. Epub 2020 Dec 18.

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium; Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, Katholieke Universiteit Leuven, Leuven, Belgium. Electronic address:

Background & Aims: Despite the growing recognition of duodenal alterations in the pathophysiology of functional dyspepsia (FD), the effect and mechanism of proton pump inhibitors (PPIs) or first-line therapy remain unclear. We studied duodenal and systemic alterations in relation to PPI therapy in patients with FD and healthy volunteers (HVs).

Methods: We performed a prospective interventional study assessing symptoms (Patient Assessment of Gastrointestinal Symptom Severity Index), duodenal alterations, and systemic factors in patients with FD ("FD-starters") and HVs before and after PPI therapy (pantoprazole 40 mg once daily for 4 weeks). Duodenal mucosal eosinophils, mast cells and permeability were quantified. Luminal pH and bile salts were determined in duodenal aspirates. Procedures were also performed in PPI-refractory patients with FD ("FD-stoppers") before and 8 weeks after PPI withdrawal. Between- and within-group changes from baseline and associations with duodenal or systemic factors were analyzed using linear mixed models.

Results: The study was completed by 30 HV, 27 FD-starters, and 18 FD-stoppers. Symptoms and duodenal eosinophils, mast cells (all, P < .0001), and paracellular passage (P = .02) were significantly higher in FD-starters vs HVs and reduced with PPI therapy. Symptoms and duodenal immune cells also decreased in FD-stoppers off PPIs. In contrast, immune cells and permeability increased in HVs on PPIs. Dyspeptic symptoms correlated with eosinophils before and during PPI therapy, and increased eosinophils and permeability in HVs on PPIs were associated with changes in bile salts.

Conclusions: We provide the first prospective evidence for eosinophil-reducing effects as a therapeutic mechanism of PPIs in FD, with differential effects in HVs pointing to a role of luminal changes. ClinicalTrials.gov, Number: NCT03545243.
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http://dx.doi.org/10.1053/j.gastro.2020.12.016DOI Listing
April 2021

Complex relationships between physiological stress and endoparasite infections in natural populations.

Curr Zool 2020 Oct 16;66(5):449-457. Epub 2020 Jun 16.

Department of Veterinary Medicine, Università degli Studi di Milano, Via Celoria 10, Milano, 2133, Italy.

Short-term elevation of glucocorticoids (GCs) is one of the major physiological mechanisms by which vertebrates cope with challenging environmental or social factors (stressors). However, when exposure to stressors occurs repeatedly or over a prolonged period of time, animals may experience chronic elevation of GCs, which reduces the immune response efficiency and can lead to higher intensity of parasitic infection. Here, we used invasive gray squirrels introduced in Northern Italy and their 2 most prevalent gastrointestinal parasites, the nematode and coccidia of the genus , as a model to investigate relationships among macroparasite infection and concentrations of fecal glucocorticoid metabolites (FGMs), an integrated measure of circulating GCs. Our results revealed an association of FGMs with infection by , but not with coccidia. Individuals with higher FGMs appear to be responsible for the greatest egg shedding within gray squirrel populations, thus possibly acting as superspreaders. However, FGMs were negatively associated with adult , suggesting that the abundance of adults of this nematode species does not induce elevation in FGMs, but is only affected by it through immune-mediated effects on its fecundity. Finally, the relationship between (both eggs and adult parasites) and FGMs was not linear, suggesting that only high levels of physiological stress influence parasite infection. Our findings highlight that the direction and magnitude of the stress-infection relationship may depend not only on the specific host-parasite system, but also on the different life stages of the same parasite.
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http://dx.doi.org/10.1093/cz/zoaa029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705514PMC
October 2020

Association between duodenal bile salts and gastric emptying in patients with functional dyspepsia.

Gut 2021 11 25;70(11):2208-2210. Epub 2020 Nov 25.

Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium

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http://dx.doi.org/10.1136/gutjnl-2020-323598DOI Listing
November 2021

Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism.

Sci Rep 2020 10 15;10(1):17448. Epub 2020 Oct 15.

Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Herestraat 49, Box 701, 3000, Leuven, Belgium.

Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P < 0.01), increased duodenal permeability (P < 0.01) and lower protein expression of claudin-3 (P < 0.001). Protein expression of tryptase (P < 0.001) was increased after acid perfusion. Nevertheless, an ultrastructural examination did not reveal degranulation of mast cells. DSCG did not modify the drop in IGP and barrier dysfunction induced by acid. Duodenal acidification activates an inhibitory duodenogastric motor reflex and, impairs epithelial integrity in healthy volunteers. However, these acid mediated effects occur independently from mast cell activation.
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http://dx.doi.org/10.1038/s41598-020-74491-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562901PMC
October 2020

Celiac Disease Remission With Tofacitinib: A Case Report.

Ann Intern Med 2020 10 28;173(7):585. Epub 2020 Jul 28.

University Hospitals Leuven, Leuven, Belgium (L.W., T.V., M.H.).

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http://dx.doi.org/10.7326/L20-0497DOI Listing
October 2020

Stress-induced changes in healthy mice do not reflect functional dyspepsia pathophysiology.

Neurogastroenterol Motil 2020 09 15;32(9):e13940. Epub 2020 Jul 15.

Translational Research in Gastrointestinal Diseases (TARGID), KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1111/nmo.13940DOI Listing
September 2020

Geographical Distribution of Ljungan Virus in Small Mammals in Europe.

Vector Borne Zoonotic Dis 2020 09 2;20(9):692-702. Epub 2020 Jun 2.

Sezione Zoologia dei Vertebrati, MUSE-Museo delle Scienze, Trento, Italy.

Ljungan virus (LV), which belongs to the genus in the family, was first isolated from bank voles () in Sweden in 1998 and proposed as a zoonotic agent. To improve knowledge of the host association and geographical distribution of LV, tissues from 1685 animals belonging to multiple rodent and insectivore species from 12 European countries were screened for LV-RNA using reverse transcriptase (RT)-PCR. In addition, we investigated how the prevalence of LV-RNA in bank voles is associated with various intrinsic and extrinsic factors. We show that LV is widespread geographically, having been detected in at least one host species in nine European countries. Twelve out of 21 species screened were LV-RNA PCR positive, including, for the first time, the red vole () and the root or tundra vole ( formerly ), as well as in insectivores, including the bicolored white-toothed shrew () and the Valais shrew (). Results indicated that bank voles are the main rodent host for this virus (overall RT-PCR prevalence: 15.2%). Linear modeling of intrinsic and extrinsic factors that could impact LV prevalence showed a concave-down relationship between body mass and LV occurrence, so that subadults had the highest LV positivity, but LV in older animals was less prevalent. Also, LV prevalence was higher in autumn and lower in spring, and the amount of precipitation recorded during the 6 months preceding the trapping date was negatively correlated with the presence of the virus. Phylogenetic analysis on the 185 base pair species-specific sequence of the 5' untranslated region identified high genetic diversity (46.5%) between 80 haplotypes, although no geographical or host-specific patterns of diversity were detected.
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http://dx.doi.org/10.1089/vbz.2019.2542DOI Listing
September 2020

A survey on the impact of the COVID-19 pandemic on motility and functional investigations in Europe and considerations for recommencing activities in the early recovery phase.

Neurogastroenterol Motil 2020 07;32(7):e13926

Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium.

Background: The COVID-19 pandemic, declared by WHO on March 13, 2020, had a major global impact on the healthcare system and services. In the acute phase, the presence of the SARS-CoV-2 virus in the aerodigestive tract limited activities in the gastroenterology clinic and procedures to emergencies only. Motility and function testing was interrupted and as we enter the recovery phase, restarting these procedures requires a safety-focused approach with adequate infection prevention for patients and healthcare professionals.

Methods: We summarized knowledge on the presence of the SARS-CoV-2 virus in the aerodigestive tract and the risk of spread with motility and functional testing. We surveyed 39 European centers documenting how the pandemic affected activities and which measures they are considering for restarting these measurements. We propose recommendations based on current knowledge as applied in our center.

Results: Positioning of catheters for gastrointestinal motility tests carries a concern for aerosol-borne infection of healthcare workers. The risk is low with breath tests. The surveyed centers stopped almost all motility and function tests from the second half of March. The speed of restarting and the safety measures taken varied highly.

Conclusions And Inferences: Based on these findings, we provided recommendations and practical relevant information for motility and function test procedures in the COVID-19 pandemic era, to guarantee a high-quality patient care with adequate infection prevention.
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http://dx.doi.org/10.1111/nmo.13926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300498PMC
July 2020

Relationships between personality traits and the physiological stress response in a wild mammal.

Curr Zool 2020 Apr 16;66(2):197-204. Epub 2019 Aug 16.

Department of Theoretical and Applied Sciences, Environment Analysis and Management Unit - Guido Tosi Research Group - Università degli Studi dell'Insubria, Via J. H. Dunant 3, 21100 Varese, Italy.

Glucocorticoids (GCs) are involved in the regulation of an animal's energetic state. Under stressful situations, they are part of the neuroendocrine response to cope with environmental challenges. Animals react to aversive stimuli also through behavioral responses, defined as coping styles. Both in captive and wild populations, individuals differ in their behavior along a proactive-reactive continuum. Proactive animals exhibit a bold, active-explorative and social personality, whereas reactive ones are shy, less active-explorative and less social. Here, we test the hypothesis that personality traits and physiological responses to stressors covary, with more proactive individuals having a less pronounced GC stress response. In wild populations of invasive gray squirrels , we measured fecal glucocorticoid metabolites (FGMs), an integrated measure of circulating GCs, and 3 personality traits (activity, sociability, and exploration) derived from open field test (OFT) and mirror image stimulation (MIS) test. Gray squirrels had higher FGMs in Autumn than in Winter and males with scrotal testes had higher FGMs than nonbreeding males. Personality varied with body mass and population density. Squirrels expressed more activity-exploration at higher than at lower density and heavier squirrels had higher scores for activity-exploration than animals that weighed less. Variation in FGM concentrations was not correlated with the expression of the 3 personality traits. Hence, our results do not support a strong association between the behavioral and physiological stress responses but show that in wild populations, where animals experience varying environmental conditions, the GC endocrine response and the expression of personality are uncorrelated traits among individuals.
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http://dx.doi.org/10.1093/cz/zoz040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233610PMC
April 2020

Spillover of an alien parasite reduces expression of costly behaviour in native host species.

J Anim Ecol 2020 07 14;89(7):1559-1569. Epub 2020 Apr 14.

Department of Veterinary Sciences and Public Health, Università degli Studi di Milano, Milan, Italy.

Understanding the effects of invasive alien species (IAS) on native host-parasite relationships is of importance for enhancing ecological theory and IAS management. When IAS and their parasite(s) invade a guild, the effects of interspecific resource competition and/or parasite-mediated competition can alter existing native host-parasite relationships and the dependent biological traits such as native species' behaviour. We used a natural experiment of populations of native red squirrels Sciurus vulgaris that were colonized by the alien grey squirrel Sciurus carolinensis, comparing repeated measurements of red squirrel parasite infection and personality with those taken in sites where only the native species occurred. We explored two alternative hypotheses: (a) individual differences in personality traits (activity and/or sociability) of native red squirrel positively affect the probability of macroparasite spillover and thus the likelihood to acquire the alien's parasitic helminth Strongyloides robustus; (b) the combined effects of grey squirrel presence and parasite infection result in a reduction of costly personality traits (activity and/or exploration). Using data from 323 arena tests across three experimental (native species and IAS) and three control sites (only native species), we found negative correlations between native species' activity and infection with S. robustus in the sites invaded by the alien species. Activity was also negatively correlated with infection by its native helminth Trypanoxyuris sciuri but only when grey squirrels were present, while in the red-only sites there was no relationship of T. sciuri infection with any of the personality traits. Moreover, individuals that acquired S. robustus during the study reduced their activity after infection, while this was not the case for animals that remained uninfected. Our results show that parasite-mediated competition is costly, reducing activity in individuals of the native species, and altering the native host-native parasite relationships.
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http://dx.doi.org/10.1111/1365-2656.13219DOI Listing
July 2020

Duodenal inflammation: an emerging target for functional dyspepsia?

Expert Opin Ther Targets 2020 06 19;24(6):511-523. Epub 2020 Apr 19.

Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, Australia.

: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders and is classified into postprandial distress and epigastric pain syndrome. Despite the recognition of duodenal inflammation as a potential trigger of symptoms, only limited anti-inflammatory therapies exist.: This narrative review summarizes the recent advances in the pathophysiology and treatment of FD; it identifies potential therapeutic targets and gaps in the field. An electronic literature search was conducted in Pubmed up to 31st of December 2019.: There is compelling evidence for the role of duodenal inflammation and the eosinophil-mast cell axis in the pathogenesis of dyspeptic symptoms. Traditional prokinetic drugs and neuromodulators target gastric dysmotility and visceral hypersensitivity but are hampered by limited efficacy and side effects. Independent of acid suppression, the anti-inflammatory action of proton pump inhibitors, which remain the first-line therapy in FD, may also explain their therapeutic effect. Other existing and newly established anti-inflammatory drugs should be investigated while trials including probiotics and selective antibiotics should examine the host microbiome and immune activation. Targeted treatments for potential causes of duodenal pathology, such as impaired permeability and dysbiosis, are likely to emerge in the future.
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http://dx.doi.org/10.1080/14728222.2020.1752181DOI Listing
June 2020

Prokinetic Effects and Symptom Relief in the Pharmacotherapy of Gastroparesis.

Gastroenterology 2020 05 18;158(6):1841-1842. Epub 2020 Feb 18.

Translational Research in Gastrointestinal Diseases (TARGID), KU Leuven, Leuven, Belgium; Gastroenterology and Hepatology Unit, University Hospitals Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1053/j.gastro.2019.06.049DOI Listing
May 2020

Novel concepts in the pathophysiology and treatment of functional dyspepsia.

Gut 2020 03 29;69(3):591-600. Epub 2019 Nov 29.

Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

Emerging data increasingly point towards the duodenum as a key region underlying the pathophysiology of functional dyspepsia (FD), one of the most prevalent functional GI disorders. The duodenum plays a major role in the control and coordination of gastroduodenal function. Impaired duodenal mucosal integrity and low-grade inflammation have been associated with altered neuronal signalling and systemic immune activation, and these alterations may ultimately lead to dyspeptic symptoms. Likely luminal candidates inducing the duodenal barrier defect include acid, bile, the microbiota and food antigens although no causal association with symptoms has been convincingly demonstrated. Recognition of duodenal pathology in FD will hopefully lead to the discovery of new biomarkers and therapeutic targets, allowing biologically targeted rather than symptom-based therapy. In this review, we summarise the recent advances in the diagnosis and treatment of FD with a focus on the duodenum.
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http://dx.doi.org/10.1136/gutjnl-2019-318536DOI Listing
March 2020
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