Diverticular disease is a common clinical problem, particularly in industrialized countries. In most cases, colonic diverticula remain asymptomatic throughout life and sometimes are found incidentally during colonic imaging in colorectal cancer screening programs in otherwise healthy subjects. Nonetheless, roughly 25% of patients bearing colonic diverticula develop clinical manifestations. Abdominal symptoms associated with diverticula in the absence of inflammation or complications are termed symptomatic uncomplicated diverticular disease (SUDD). The pathophysiology of diverticular disease as well as the mechanisms involved in the shift from an asymptomatic condition to a symptomatic one is still poorly understood. It is accepted that both genetic factors and environment, as well as intestinal microenvironment alterations, have a role in diverticula development and in the different phenotypic expressions of diverticular disease. In the present review, we will summarize the up-to-date knowledge on the pathophysiology of diverticula and their different clinical setting, including diverticulosis and SUDD.

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.

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 Ca²⁺ 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.

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.

Eosinophilic gastrointestinal diseases (EGIDs) are an emerging group of pathological entities characterized by an eosinophil-predominant infiltration of different tracts of the gut in the absence of secondary causes of eosinophilia. According to the specific tract of the gut involved, EGIDs can be classified into eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The epidemiology of EGIDs is evolving rapidly. EoE, once considered a rare disease, now has an incidence and prevalence of 7.7 new cases per 100,000 inhabitants per years and 34.4 cases per 100,000 inhabitants per year, respectively. Fewer data are available regarding non-EoE EGIDs, whose prevalence are estimated to range between 2.1 and 17.6 in 100,000 individuals, depending on age, sex, and ethnicity. Diagnosis requires the presence of suggestive symptoms, endoscopic biopsies showing abnormal values of eosinophils infiltrating the gut, and exclusion of secondary causes of eosinophilia. EoE typically presents with dysphagia and episodes of food bolus impactions, while EoG, EoN, and EoC may all present with abdominal pain and diarrhea, with or without other non-specific symptoms. In addition, although different EGIDs are currently classified as different entities, there may be overlap between different diseases in the same patient. Despite EGIDs being relatively novel pathological entities, the research on possible treatments is rapidly growing. In this regard, several randomized controlled trials are currently ongoing to investigate novel molecules, including ad-hoc steroid formulations, immunosuppressants, and mostly monoclonal antibodies that target the specific molecular mediators of EGIDs. This narrative review provides an up-to-date overview of available and investigational drugs for different EGIDs.

INTRODUCTION: Consumption of green kiwifruit is known to relieve constipation. Previous studies have also reported improvements in gastrointestinal (GI) comfort. We investigated the effect of consuming green kiwifruit on GI function and comfort. METHODS: Participants included healthy controls (n = 63), patients with functional constipation (FC, n = 60), and patients with constipation-predominant irritable bowel syndrome (IBS-C, n = 61) randomly assigned to consume 2 green kiwifruits or psyllium (7.5 g) per day for 4 weeks, followed by a 4-week washout, and then the other treatment for 4 weeks. The primary outcome was the number of complete spontaneous bowel movements (CSBM) per week. Secondary outcomes included GI comfort which was measured using the GI symptom rating scale, a validated instrument. Data (intent-to-treat) were analyzed as difference from baseline using repeated measures analysis of variance suitable for AB/BA crossover design. RESULTS: Consumption of green kiwifruit was associated with a clinically relevant increase of ≥ 1.5 CSBM per week (FC; 1.53, P < 0.0001, IBS-C; 1.73, P = 0.0003) and significantly improved measures of GI comfort (GI symptom rating scale total score) in constipated participants (FC, P < 0.0001; IBS-C, P < 0.0001). No significant adverse events were observed. DISCUSSION: This study provides original evidence that the consumption of a fresh whole fruit has demonstrated clinically relevant increases in CSBM and improved measures of GI comfort in constipated populations. Green kiwifruits are a suitable dietary treatment for relief of constipation and associated GI comfort.