Publications by authors named "Giovanni Barbara"

136 Publications

Corrigendum: Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier.

Front Nutr 2021 1;8:790387. Epub 2021 Nov 1.

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

[This corrects the article DOI: 10.3389/fnut.2021.718356.].
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http://dx.doi.org/10.3389/fnut.2021.790387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591313PMC
November 2021

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study.

Am J Gastroenterol 2022 01;117(1):147-157

Ege University Department of Infectious Diseases, Izmir, Turkey.

Introduction: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month.

Methods: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire.

Results: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels.

Discussion: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.
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http://dx.doi.org/10.14309/ajg.0000000000001541DOI Listing
January 2022

Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier.

Front Nutr 2021 13;8:718356. Epub 2021 Sep 13.

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

The intestinal epithelial barrier (IEB) is one of the largest interfaces between the environment and the internal milieu of the body. It is essential to limit the passage of harmful antigens and microorganisms and, on the other side, to assure the absorption of nutrients and water. The maintenance of this delicate equilibrium is tightly regulated as it is essential for human homeostasis. Luminal solutes and ions can pass across the IEB two main routes: the transcellular pathway or the paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible for the regulation of paracellular permeability. TJs control the passage of antigens through the IEB and have a key role in maintaining barrier integrity. Several factors, including cytokines, gut microbiota, and dietary components are known to regulate intestinal TJs. Gut microbiota participates in several human functions including the modulation of epithelial cells and immune system through the release of several metabolites, such as short-chain fatty acids (SCFAs). Mediators released by immune cells can induce epithelial cell damage and TJs dysfunction. The subsequent disruption of the IEB allows the passage of antigens into the mucosa leading to further inflammation. Growing evidence indicates that dysbiosis, immune activation, and IEB dysfunction have a role in several diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gluten-related conditions. Here we summarize the interplay between the IEB and gut microbiota and mucosal immune system and their involvement in IBS, IBD, and gluten-related disorders.
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http://dx.doi.org/10.3389/fnut.2021.718356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475765PMC
September 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

Gastrointestinal Bleeding in COVID-19 Patients: A Systematic Review with Meta-Analysis.

Can J Gastroenterol Hepatol 2021 1;2021:2534975. Epub 2021 Sep 1.

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

The novel coronavirus disease 2019 (COVID-19) has been reported to affect the gastrointestinal system with a variety of symptoms, including bleeding. The prevalence of bleeding in these patients remains unclear. The aim of this meta-analysis is to estimate the rate of gastrointestinal bleeding in COVID-19 patients and its association with mortality. MEDLINE and Embase were searched through December 20, 2020. Studies reporting COVID-19 patients with and without gastrointestinal bleeding were included. Estimated prevalence with 95% confidence intervals (CI) was pooled; heterogeneity was expressed as . Metaregression analysis was performed to assess the impact of confounding covariates. Ten studies met the inclusion criteria and were included in the analysis. A total of 91887 COVID-19 patients were considered, of whom 534 reported gastrointestinal bleeding (0.6%) [409 (76.6%) upper and 121 (22.7%) lower gastrointestinal bleeding (UGIB and LGIB, resp.)]. The overall pooled gastrointestinal bleeding rate was 5% [95% CI 2-8], with high heterogeneity ( 99.2%); "small study effect" was observed using the Egger test (=0.049). After removing two outlier studies, the pooled bleeding rate was 2% [95% CI 0-4], with high heterogeneity ( 99.2%), and no "small study effect" (=0.257). The pooled UGIB rate was 1% (95% CI 0-3, 98.6%, =0.214), whereas the pooled LGIB rate was 1% (95% CI 0-2, 64.7%, =0.919). Metaregression analysis showed that overall estimates on gastrointestinal bleeding were affected by studies reporting different sources of bleeding. No significant association between gastrointestinal bleeding and mortality was found. In this meta-analysis of published studies, individuals with COVID-19 were found to be at risk for gastrointestinal bleeding, especially upper gastrointestinal bleeding.
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http://dx.doi.org/10.1155/2021/2534975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429023PMC
September 2021

An unusual cause of diarrhoea: case report and literature review of olmesartan-associated enteropathy.

Eur J Gastroenterol Hepatol 2021 Dec;33(1S Suppl 1):e1060-e1066

Department of Medical and Surgical Sciences.

Olmesartan is an angiotensin II receptor blocker, approved in 2002 by the Food and Drug Administration for the treatment of hypertension. During chronic therapy with olmesartan, sprue-like enteropathy can occur, being mainly characterised by non-bloody diarrhoea, weight loss and variable degrees of duodenal mucosal damage, which resolved after withdrawal of olmesartan. We hereby report the case of a 77-year-old, poli-treated male patient with a 3-month history of diarrhoea, vomiting and weight loss, associated with severe intestinal villous atrophy and lymphocytic infiltration of gastric and colonic mucosa. After extensive investigations aimed at excluding other possible causes of chronic diarrhoea, a diagnosis of olmesartan-associated enteropathy was made, which was later confirmed by clinical improvement after the discontinuation of the drug. Repeated endoscopy 8 months later showed complete healing of duodenal mucosa with normal villous architecture. Villous atrophy and lymphocytic infiltration of duodenal mucosa are the most described pathologic finding, but several cases of gastric and colonic involvement have also been reported. We, therefore, reviewed the available literature, focussing on the extent of mucosal damage throughout the whole intestine and on its possible causative factors.
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http://dx.doi.org/10.1097/MEG.0000000000002208DOI 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

Implications of SARS-CoV-2 infection for neurogastroenterology.

Neurogastroenterol Motil 2021 03 16;33(3):e14104. Epub 2021 Feb 16.

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Background: Coronavirus disease 2019 (COVID-19) is associated with gastrointestinal and hepatic manifestation in up to one fifth of patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, infects gastrointestinal epithelial cells expressing angiotensin-converting enzyme 2 (ACE2) receptors triggering a cascade of events leading to mucosal and systemic inflammation. Symptomatic patients display changes in gut microbiota composition and function which may contribute to intestinal barrier dysfunction and immune activation. Evidence suggests that SARS-CoV-2 infection and related mucosal inflammation impact on the function of the enteric nervous system and the activation of sensory fibers conveying information to the central nervous system, which, may at least in part, contribute symptom generation such as vomiting and diarrhea described in COVID-19. Liver and pancreas dysfunctions have also been described as non-respiratory complications of COVID-19 and add further emphasis to the common view of SARS-CoV-2 infection as a systemic disease with multiorgan involvement.

Purpose: The aim of this review was to highlight the current knowledge on the pathophysiology of gastrointestinal SARS-CoV-2 infection, including the crosstalk with the gut microbiota, the fecal-oral route of virus transmission, and the potential interaction of the virus with the enteric nervous system. We also review the current available data on gastrointestinal and liver manifestations, management, and outcomes of patients with COVID-19.
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http://dx.doi.org/10.1111/nmo.14104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995160PMC
March 2021

Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders.

Nutrients 2020 Dec 4;12(12). Epub 2020 Dec 4.

IRCCS S. Orsola, 40138 Bologna, Italy.

Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut-brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut-brain interaction.
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http://dx.doi.org/10.3390/nu12123735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761787PMC
December 2020

Managing the Inevitable Surge of Post-COVID-19 Functional Gastrointestinal Disorders.

Am J Gastroenterol 2021 01;116(1):4-7

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

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http://dx.doi.org/10.14309/ajg.0000000000001062DOI Listing
January 2021

An international survey on clinicians' perspectives on the diagnosis and management of chronic intestinal pseudo-obstruction and enteric dysmotility.

Neurogastroenterol Motil 2020 12 22;32(12):e13937. Epub 2020 Jul 22.

University of Manchester, Manchester, UK.

Background: Chronic intestinal pseudo-obstruction (CIPO) and enteric dysmotility (ED) are small intestinal motility disorders defined by radiological and manometric criteria. In the absence of consensus guidelines, we surveyed opinions on the diagnosis and management of CIPO and ED among experts from different countries.

Methods: A survey questionnaire was circulated electronically to members of the European society for Clinical Nutrition and Metabolism, European Society of Neurogastroenterology and Motility, and United European Gastroenterology. Only responses from participants completing all required components were included.

Key Results: Of 154 participants, 93% agreed that CIPO and ED should be classified separately. Overall, 73% reported an increasing incidence of CIPO and ED, with hypermobile Ehlers-Danlos Syndrome the group with the largest increase in referrals (37%), particularly in the UK (P < .0001). The majority (95%) find diagnosing CIPO and ED difficult. Notably, antroduodenal manometry, a test mandated to diagnose ED, is infrequently used (only 21% respondents use in >50% cases) and full thickness biopsies were reported to seldom influence medical treatment, nutritional management, and prognosis. Respondents reported that very few treatments are useful for most patients, with bacterial overgrowth treatment, prucalopride, and psychological therapies felt to be the most useful. While only 23% of clinicians felt that parenteral nutrition (PN) improves gastrointestinal symptoms in >50% of cases, 68% reported PN dependency at 5 years in the majority of cases.

Conclusions And Inferences: These data highlight the difficulties with diagnosing and managing CIPO and ED and underscore the urgent need for international, multidisciplinary, clinical practice guidelines.
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http://dx.doi.org/10.1111/nmo.13937DOI Listing
December 2020

Distinguishing features between patients with acute diverticulitis and diverticular bleeding: Results from the REMAD registry.

Dig Liver Dis 2021 02 16;53(2):202-209. Epub 2020 Jun 16.

Medical-Surgical Department of Clinical Sciences and Translational Medicine, University Sapienza, via di Grottarossa 1035-1039, 00189 Rome, Italy.

Background: Pathogenesis of acute diverticulitis and diverticular bleeding remains poorly defined, and few data compare directly risk factors for these complications.

Aims: to assess differences in clinical features, lifestyles factors and concurrent drug use in patients with acute diverticulitis and those with diverticular bleeding.

Methods: Data were obtained from the REMAD Registry, an ongoing 5-year prospective, observational, multicenter, cohort study conducted on 1,217 patients. Patient- and clinical- related factors were compared among patients with uncomplicated diverticular disease, patients with previous acute diverticulitis, and patients with previous diverticular bleeding.

Results: Age was significantly lower (OR 0.48, 95% CI: 0.34-0.67) and family history of diverticular disease was significantly higher (OR 1.60, 95% CI: 1.11-2.31) in patients with previous diverticulitis than in patients with uncomplicated diverticular disease, respectively. Chronic obstructive pulmonary disease was significantly higher in patients with previous diverticular bleeding as compared with both uncomplicated diverticular disease (OR 8.37, 95% CI: 2.60-27.0) and diverticulitis (OR 4.23, 95% CI: 1.11-16.1).

Conclusion: This ancillary study from a nationwide Registry showed that some distinctive features identify patients with acute diverticulitis and diverticular bleeding. These information might improve the assessment of risk factors for diverticular complications.
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http://dx.doi.org/10.1016/j.dld.2020.05.045DOI Listing
February 2021

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

Faecal microbial transplantation in IBS: ready for prime time?

Gut 2020 05 26;69(5):795-796. Epub 2020 Feb 26.

Gastroenterology Department, Policlinico A. Gemelli, Rome, Italy.

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http://dx.doi.org/10.1136/gutjnl-2019-320411DOI Listing
May 2020

Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity.

Gut 2020 11 14;69(11):1966-1974. Epub 2020 Feb 14.

Department of Medical and Surgical Sciences, University of Bologna, Bologna, Emilia-Romagna, Italy

Objective: Non-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers are available to diagnose NCGS and the gold standard double-blind placebo-controlled gluten challenge is clinically impractical. The aim of our work was to investigate the role of serum zonulin as a diagnostic biomarker of NCGS and to develop a diagnostic algorithm.

Design: In a multicentre study, we enrolled 86 patients with either self-reported or double-blind confirmed NCGS, 59 patients with diarrhoea-predominant IBS (IBS-D), 15 patients with CD and 25 asymptomatic controls (AC). Zonulin serum levels were assessed and the associated diagnostic power calculated. Clinical and symptomatic data were recorded. The effect of diet on zonulin levels was evaluated in a subgroup of patients with NCGS.

Results: Compared with ACs, the NCGS, irrespective of modality of diagnosis, and patients with CD had significantly increased levels of zonulin, as did both NCGS and patients with CD compared with participants with IBS-D. Self-reported NCGS showed increased zonulin levels compared with double-blind confirmed and not-confirmed NCGS. Six-month wheat avoidance significantly reduced zonulin levels only in HLA-DQ2/8-positive participants with NCGS. The diagnostic accuracy of zonulin levels in distinguishing NCGS from IBS-D was 81%. After exclusion of CD, a diagnostic algorithm combining zonulin levels, symptoms and gender improved the accuracy to 89%.

Conclusion: Zonulin can be considered a diagnostic biomarker in NCGS and combined with demographic and clinical data differentiates NCGS from IBS-D with high accuracy. Wheat withdrawal was associated with a reduction in zonulin levels only in NCGS carrying HLA genotype.
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http://dx.doi.org/10.1136/gutjnl-2019-319281DOI Listing
November 2020

Course of the Diverticular Disease: What is changing?

J Gastrointestin Liver Dis 2019 Dec 19;28(suppl. 4):11-16. Epub 2019 Dec 19.

Department of Clinical and Experimental Medicine, University "Federico II", Naples, Italy.

In this session several critical issues in diverticular disease were considered, including "It is Symptomatic Diverticular Disease or Irritable Bowel Syndrome?", "What do determine evolution to diverticulitis, bowel habits alteration or inflammation?", and "Prevention of acute diverticulitis: Is it at all possible?". The first talking compared symptoms and laboratory findings between Symptomatic Uncomplicated Diverticular Disease  (SUDD) and Irritable Bowel Syndrome (IBS). Although both disease share some symptoms, and although IBS can occur in patients having diverticulosis,  SUDD and IBS can be differentiate using a combination of symptoms and laboratory tools. The second talking debated what are the most important risk factors for the evolution towards acute diverticulitis. Current data seem to exclude a significant role of bowel habits alteration, while inflammation seems to have a stronger role, especially in causing acute diverticulitis recurrence. The third talking analyzed about the acute diverticulitis prevention. Primary prevention seem to be little better when using mesalazine, while no definite conclusion can be drawn about the use of fiber and rifaximin. About the secondary prevention, no drugs can be currently advised due to lacking of definite results. At the same time, surgery should be advised on case-by-case basis.
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http://dx.doi.org/10.15403/jgld-552DOI Listing
December 2019

Hot Topics in Medical Treatment of Diverticular Disease: Evidence Pro and Cons.

J Gastrointestin Liver Dis 2019 Dec 19;28(suppl. 4):23-29. Epub 2019 Dec 19.

Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany.

Symptomatic Uncomplicated Diverticular Disease (SUDD) is the most common clinical form of Diverticular Disease (DD). The therapy should be aimed at reducing both the intensity and frequency of symptoms as well as preventing complications. The pharmacological treatments include fibers, not absorbable antibiotics (for example rifaximin), anti-inflammatory drugs (for example 5-amino-salycilic acid) and probiotics, alone or in combination with other drugs. Although some of these treatments seem to be effective in treating SUDD, but their efficacy in preventing complications of the disease is still uncertain. It has been hypothesized that microbial imbalance associated with bacterial overgrowth of the colon, may be the key to the development of diverticular disease (DD). Therefore, drugs that can manipulate gut microbiota such as probiotics or rifaximine are considered as a potential key therapy. Rifaximine is able to modulate the intestinal ecosystem, restoring eubiosis. Traditionally, DD of the colon is thought to be related to low grade of inflammation. By analogy with other inflammatory bowel diseases mesalazine has been studied also in DD. There are several evidences that may support the use of mesalazine in the SUDD. Unfortunately, mesalazine cannot be used to prevent diverticulitis because of the paucity of high-quality studies. Currently, mesalazine has a limited place for the management of SUDD. In SUDD probiotics have been proven as an effective therapy in reducing abdominal symptoms, but unfortunately there has been limited number of relevant studies regarding efficacy of this therapy.
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http://dx.doi.org/10.15403/jgld-554DOI Listing
December 2019

The DICA Endoscopic Classification for Diverticular Disease of the Colon Shows a Significant Interobserver Agreement among Community Endoscopists: an International Study.

J Gastrointestin Liver Dis 2019 Dec 19;28(suppl. 4):39-44. Epub 2019 Dec 19.

Department of Colorectal Surgery, King's College Hospital, London, United Kingdom.

Background And Aims: The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting.

Methods: A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of interrater agreement.

Results: Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal κ was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications.

Conclusions: The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD.
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http://dx.doi.org/10.15403/jgld-558DOI Listing
December 2019

International Consensus on Diverticulosis and Diverticular Disease. Statements from the 3rd International Symposium on Diverticular Disease.

J Gastrointestin Liver Dis 2019 Dec 19;28(suppl. 4):57-66. Epub 2019 Dec 19.

Division of Internal Medicine and Gastroenterology, CIC "Columbus", Catholic University - "A. Gemelli" University Hospital, Rome, Italy.

The statements produced by the Chairmen and Speakers of the 3rd International Symposium on Diverticular Disease, held in Madrid on April 11th-13th 2019, are reported. Topics such as current and evolving concepts on the pathogenesis, the course of the disease, the news in diagnosing, hot topics in medical and surgical treatments, and finally, critical issues on the disease were reviewed by the Chairmen who proposed 39 statements graded according to level of evidence and strength of recommendation. Each topic was explored focusing on the more relevant clinical questions. The vote was conducted on a 6-point scale and consensus was defined a priori as 67% agreement of the participants. The voting group consisted of 124 physicians from 18 countries, and agreement with all statements was provided. Comments were added explaining some controversial areas.
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http://dx.doi.org/10.15403/jgld-562DOI Listing
December 2019

µ-opioid receptor, β-endorphin, and cannabinoid receptor-2 are increased in the colonic mucosa of irritable bowel syndrome patients.

Neurogastroenterol Motil 2019 11 23;31(11):e13688. Epub 2019 Jul 23.

Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Background And Aims: The gut immune, cannabinoid, and opioid systems constitute an integrated network contributing to visceral sensation and pain modulation. We aimed to assess the expression of the µ-opioid receptor (MOR), its ligand β-endorphin (β-END), and cannabinoid receptor-2 (CB ) in patients with irritable bowel syndrome (IBS) and asymptomatic controls (AC) and their correlation with sex and symptom perception.

Methods: Mucosal biopsies were obtained from the left colon of 31 IBS patients (45% women) with predominant constipation (IBS-C, 9) or diarrhea (IBS-D, 10) or with mixed bowel habits (IBS-M, 12) and 32 AC (44% women) and processed for qRT-PCR, Western blotting, and immunohistochemistry.

Key Results: µ-opioid receptor and CB mRNA and protein expression and β-END protein levels were increased in patients with IBS compared to AC (all Ps=0.021). A significant sex by IBS interaction was found in relation to CB mRNA expression (P = .003) with women showing a markedly higher expression to men (P = .035). In contrast, in AC, men had higher expression than women (P = .033). β-END, MOR, and CB immunoreactivities (IR) were localized to CD4+T cells including EMR-1+ eosinophils and CD31+ T cells but not to mast cells.

Conclusions: The increased expression of MOR, β-END, and CB in the mucosa of IBS patients, where they are localized to immune cells, suggests that opioid and cannabinoid systems play an immune-related compensatory role in visceral pain in IBS patients. Further work is necessary to support this hypothesis.
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http://dx.doi.org/10.1111/nmo.13688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791736PMC
November 2019

Italian nationwide survey of pharmacologic treatments in diverticular disease: Results from the REMAD registry.

United European Gastroenterol J 2019 07 20;7(6):815-824. Epub 2019 Apr 20.

Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy.

Background: Although diverticular disease is a common condition, its effective treatment is challenging in clinical practice.

Objective: The objective of this article is to assess pharmacological management in different clinical settings of diverticular disease and factors associated with treatment using the Italian registry Registro Malattia Diverticolare (REMAD).

Methods: At study enrolment, patients were categorised into subgroups: diverticulosis, symptomatic uncomplicated diverticular disease and previous diverticulitis. We registered demographic, clinical and lifestyle factors, quality of life and the use of treatments for diverticular disease in the last year. Logistic regression analysis assessed the association between clinical factors and treatment consumption.

Results: A total of 500 of the 1206 individuals included had had at least one treatment for diverticular disease in the last year: 23.6% (166/702) of patients with diverticulosis, 55.9% (165/295) of patients with symptomatic diverticular disease, and 80.9% (169/209) of patients with previous diverticulitis ( < 0.001). In multivariate analysis, the following factors were significantly associated with treatment use: female gender, family history of colonic diverticula, organic digestive comorbidity and impaired physical quality of life components.

Conclusion: Individuals with diverticular disease take medications based on the different clinical settings of disease. We identified different features associated with treatment use in the distinct clinical entities of diverticular disease. NCT03325829.
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http://dx.doi.org/10.1177/2050640619845990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620876PMC
July 2019

Nerve fiber overgrowth in patients with symptomatic diverticular disease.

Neurogastroenterol Motil 2019 09 5;31(9):e13575. Epub 2019 Mar 5.

Department of Medical and Surgical Sciences and Center for Applied Biomedical Research (CRBA), Alma Mater Studiorum - University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.

Background: Colonic diverticulosis is a common condition in industrialized countries. Up to 25% of patients with diverticula develop symptoms, a condition termed symptomatic uncomplicated diverticular disease (SUDD). The aim of the present study was to characterize neuroimmune interactions and nerve fiber plasticity in the colonic mucosa of patients with diverticula.

Methods: Controls, patients with diverticulosis and with SUDD were enrolled in the study. Mucosal biopsies were obtained close to diverticula (diverticular region) and in a normal mucosa (distant site), corresponding to sigmoid and descending colon in the controls. Quantitative immunohistochemistry was used to assess mast cells, T cells, macrophages, nerve fibers, and neuronal outgrowth (growth-associated protein 43, GAP43+fibers).

Key Results: No difference emerged in mast cells and T cells among the three groups. Macrophages were increased in patients with SUDD and diverticulosis as compared to controls. Nerve fibers were enhanced in patients with SUDD and diverticulosis in comparison with controls in the diverticular region. GAP43+ fibers were increased only in patients with SUDD as compared to controls and to patients with diverticulosis in the diverticular region. In patients with SUDD, GAP43 density was increased in the diverticular region compared to distant site. Macrophages close to GAP43+ fibers were increased in the diverticular region of patients with SUDD. Significant correlations were found between GAP43+ fibers and immune cells.

Conclusions And Inferences: Patients with diverticula are characterized by increased macrophage counts, while nerve fiber sprouting is increased only in the diverticular region of patients with SUDD suggesting a role in symptom generation.
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http://dx.doi.org/10.1111/nmo.13575DOI Listing
September 2019

Is gastroparesis a gastric disease?

Neurogastroenterol Motil 2019 05 17;31(5):e13562. Epub 2019 Feb 17.

Department of Digestive Diseases, S. Orsola University Hospital, Bologna, Italy.

Background: Gastroparesis is a digestive syndrome characterized by delayed gastric emptying (GE) and by symptoms that are suggestive of gastroduodenal motor disorders. There are three grades of gastroparesis of increasing severity: (a) mild gastroparesis; (b) compensated gastroparesis; and (c) gastric failure. GE abnormalities are partially related to symptom type and severity, and other mechanisms may be involved.

Aim: To investigate enteric dysmotility (ED) in patients with suspected gastroparesis.

Methods: Patients with symptoms suggestive of gastroparesis were consecutively included in the study and underwent a C-octanoic acid GE breath test and small bowel manometry (SBM). Clinical features were recorded using predefined, validated questionnaires at entry.

Key Results: The study enrolled 88 patients (71 women; mean age: 37.8 ± 14.3 years). Gastric emptying was delayed in 25 patients (28.4%), and 70 patients (79.5%) presented small bowel motor abnormalities including bursts, abnormal activity fronts, inability to respond to meal ingestion, and hypocontractility. Gastric emptying was delayed in 24 of the 70 patients with ED (34.3% vs 5.5% of patients with normal SBM). Enteric dysmotility was detected in 24 of 25 patients (96%) with delayed GE. Patients with and without delayed GE showed similar moderate/severe gastroparesis manifestations, but patients with ED significantly more often had moderate/severe gastroparesis manifestations than patients with normal SBM (grade 1:14% vs 39%, grade 2:62% vs 56%, grade 3:24% vs 5%, respectively).

Conclusions And Inferences: Enteric dysmotility was more frequent than delayed GE in patients with symptoms suggestive of gastroparesis. Gastroparesis severity was associated with small bowel motor abnormalities but not with delayed GE.
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http://dx.doi.org/10.1111/nmo.13562DOI Listing
May 2019

5-oxoETE triggers nociception in constipation-predominant irritable bowel syndrome through MAS-related G protein-coupled receptor D.

Sci Signal 2018 12 18;11(561). Epub 2018 Dec 18.

INSERM, UMR1220, IRSD, Université de Toulouse, INRA, ENVT, UPS, Toulouse, France.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by chronic abdominal pain concurrent with altered bowel habit. Polyunsaturated fatty acid (PUFA) metabolites are increased in abundance in IBS and are implicated in the alteration of sensation to mechanical stimuli, which is defined as visceral hypersensitivity. We sought to quantify PUFA metabolites in patients with IBS and evaluate their role in pain. Quantification of PUFA metabolites by mass spectrometry in colonic biopsies showed an increased abundance of 5-oxoeicosatetraenoic acid (5-oxoETE) only in biopsies taken from patients with IBS with predominant constipation (IBS-C). Local administration of 5-oxoETE to mice induced somatic and visceral hypersensitivity to mechanical stimuli without causing tissue inflammation. We found that 5-oxoETE directly acted on both human and mouse sensory neurons as shown by lumbar splanchnic nerve recordings and Ca imaging of dorsal root ganglion (DRG) neurons. We showed that 5-oxoETE selectively stimulated nonpeptidergic, isolectin B4 (IB4)-positive DRG neurons through a phospholipase C (PLC)- and pertussis toxin-dependent mechanism, suggesting that the effect was mediated by a G protein-coupled receptor (GPCR). The MAS-related GPCR D (Mrgprd) was found in mouse colonic DRG afferents and was identified as being implicated in the noxious effects of 5-oxoETE. Together, these data suggest that 5-oxoETE, a potential biomarker of IBS-C, induces somatic and visceral hyperalgesia without inflammation in an Mrgprd-dependent manner. Thus, 5-oxoETE may play a pivotal role in the abdominal pain associated with IBS-C.
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http://dx.doi.org/10.1126/scisignal.aal2171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411128PMC
December 2018

Probiotics in irritable bowel syndrome: Where are we?

Neurogastroenterol Motil 2018 12;30(12):e13513

Digestive System Research Unit, Departments of Gastroenterology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona (Departamento de Medicina) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.

We have only recently begun to understand how alterations of the intestinal microbial ecosystem lead to the disruption of host-microbial interactions and are associated with diseases, including functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Although we are still far from understanding the human microbiome, gut microbiota is already a therapeutic target. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host and may represent a therapeutic option for diseases characterized by dysbiosis such as IBS. Meta-analyses suggest that probiotics provide a therapeutic gain over placebo on global symptoms with a high safety profile in IBS patients. However, the mechanisms by which they provide benefit in IBS remain virtually unknown. In this issue of Neurogastroenterology and Motility, BIO-25, a multispecies probiotic, did not significantly modify the composition of the fecal microbiota, but interestingly, patients with specific basal features of the intestinal microbial ecosystem improved with treatment. Based on these data, it is tantalizing to speculate that microbiota composition serves as a predictor of the response to probiotic intervention. This mini-review addresses unresolved issues related to mechanisms through which probiotics may exert their beneficial effects, the biological, as well as clinical predictors of favorable outcomes in IBS and finally considers possible new directions for future studies.
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http://dx.doi.org/10.1111/nmo.13513DOI Listing
December 2018

Recent advances in understanding non-celiac gluten sensitivity.

F1000Res 2018 11;7. Epub 2018 Oct 11.

Department of Medical and Surgical Sciences (DIMEC) and Center for Applied Biomedical Research (CRBA), Alma Mater Studiorum - University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.

Non-celiac gluten sensitivity (NCGS) is a condition characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing foods in the absence of celiac disease and wheat allergy. The diagnosis is cumbersome and currently confirmed only by gluten withdrawal and double-blind placebo challenge protocols. There is great overlap in symptoms between NCGS and other functional gastrointestinal disorders, making a differential diagnosis difficult. The pathophysiology of NCGS is largely unclear, and there are contrasting data on the trigger of this condition. This review will highlight the state-of-the-art knowledge on NCGS and the key open questions.
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http://dx.doi.org/10.12688/f1000research.15849.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182669PMC
March 2019

Post-infectious IBS: Defining its clinical features and prognosis using an internet-based survey.

United European Gastroenterol J 2018 Oct 23;6(8):1245-1253. Epub 2018 May 23.

Nottingham Digestive Diseases Centre, University of Nottingham and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.

Background: Gastrointestinal infection is an important risk factor for developing irritable bowel syndrome (IBS). Our aim was to characterise post-infectious IBS (PI-IBS) compared to other IBS patients.

Methods: An internet survey of IBS patients using Rome III diagnostic questionnaire, Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire-12 Somatic Symptom (PHQ12-SS) scale score documenting the mode of onset was conducted.

Results: A total of 7811 participants (63.2% female), of whom 1004 (13.3%) met criteria for PI-IBS, were studied. Seventy per cent of PI-IBS patients described sudden onset, 35% onset while travelling, 49.6% vomiting, 49.9% fever and 20.3% bloody diarrhoea. Compared to other IBS individuals, PI-IBS was significantly associated with living in Northern Europe and North America, having a hysterectomy, not having an appendicectomy, higher PHQ12-SS score and having more than one toilet in the family home. PI-IBS patients had more frequent stools. At one year recovery rate in the PI-IBS and non-PI-IBS group was 19.7% and 22.2%,  = 0.15. Recovery rates were lower for females (20.7%) vs males (38.8%), those with somatisation (23.0%) vs those without (33.2%) and those living in North America or Northern Europe (21.1%) vs living elsewhere (33.9%)  ≤ 0.001.

Conclusion: PI-IBS accounts for around 13% of all IBS in this internet sample, with some distinctive features but a similar prognosis to the remainder.
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http://dx.doi.org/10.1177/2050640618779923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169057PMC
October 2018

Pre- and probiotic overview.

Curr Opin Pharmacol 2018 12 13;43:87-92. Epub 2018 Sep 13.

Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research, University of Bologna, Bologna, Italy. Electronic address:

The dynamic relationship between gut microbiota and its human host is also known as a trophic association that might range from commensalism, where only the microbe enjoys a positive effect from the relationship, to intestinal symbiosis where both host and microbe benefit from their interaction. In the last years, we have started to understand how alterations of the gut microbiota composition leading to the disruption of host-microbial interactions are associated and/or predispose individuals to disease conditions ranging from inflammatory bowel diseases to allergy and functional gastrointestinal disorders, such as irritable bowel syndrome. While we await important insights in this field, the microbiota is already a therapeutic target. Based on the actual definitions, prebiotics are defined as substrates that are selectively utilized by host microorganisms conferring a health benefit, while probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Although their health promoting activities encompasses numerous effects, including immunostimulation, competitive exclusion of pathogens, and gut barrier enhancement, the exact mechanism of action by which these compounds exert their beneficial actions in humans is only partially known. In this review, we highlight the current insights into the clinical applications of prebiotics and probiotics in gastroenterology.
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http://dx.doi.org/10.1016/j.coph.2018.08.010DOI Listing
December 2018

Funding for gastrointestinal disease research in the European Union.

Lancet Gastroenterol Hepatol 2018 09 8;3(9):593-595. Epub 2018 Aug 8.

Institute of Human Genetics, Department of Human Molecular Genetics, University of Heidelberg, Heidelberg 69120, Germany. Electronic address:

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http://dx.doi.org/10.1016/S2468-1253(18)30203-6DOI Listing
September 2018
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