ObjectivesCOVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear.DesignThis Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death).ResultsBetween 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death.ConclusionsActive IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.

Inflammatory bowel diseases are chronic diseases affecting the gastrointestinal tract, whose major forms are represented by Crohn's disease (CD) and ulcerative colitis (UC). Their etiology is still unclear, although several factors have been identified as major determinants for induction or relapses. Among these, the role of the “forgotten organ”, gut microbiota, has become more appreciated in recent years. The delicate symbiotic relationship between the gut microbiota and the host appears to be lost in IBD. In this perspective, several studies have been conducted to assess the role of prebiotics and probiotics in gut microbiota modulation. This is a minireview aimed to address in an easy format (simple questions-simple answers) some common issues about the theme. An update on the role of selected constituents of gut microbiota in the pathogenesis of IBD is presented together with the analysis of the efficacy of gut microbiota modulation by prebiotics and probiotics administration in the management of IBD.

Ulcerative colitis (UC) is a chronic inflammatory disease, whose etiology is still unclear. Its pathogenesis involves an interaction between genetic factors, immune response and the "forgotten organ", Gut Microbiota. Several studies have been conducted to assess the role of antibiotics and probiotics as additional or alternative therapies for Ulcerative Colitis. Escherichia coli Nissle (EcN) is a nonpathogenic Gram-negative strain isolated in 1917 by Alfred Nissle and it is the active component of microbial drug Mutaflor(®) (Ardeypharm GmbH, Herdecke, Germany and EcN, Cadigroup, In Italy) used in many gastrointestinal disorder including diarrhea, uncomplicated diverticular disease and UC. It is the only probiotic recommended in ECCO guidelines as effective alternative to mesalazine in maintenance of remission in UC patients. In this review we propose an update on the role of EcN 1917 in maintenance of remission in UC patients, including data about efficacy and safety. Further studies may be helpful for this subject to further the full use of potential of EcN.

Antibiotics are mainly used in clinical practice for their activity against pathogens, but they also alter the composition of commensal gut microbial community. Rifaximin is a non-absorbable antibiotic with additional effects on the gut microbiota about which very little is known. It is still not clear to what extent rifaximin can be able to modulate gut microbiota composition and diversity in different clinical settings. Studies based on culture-dependent techniques revealed that rifaximin treatment promotes the growth of beneficial bacteria, such as Bifidobacteria and Lactobacilli. Accordingly, our metagenomic analysis carried out on patients with different gastrointestinal and liver diseases highlighted a significant increase in Lactobacilli after rifaximin treatment, persisting in the short time period. This result was independent of the disease background and was not accompanied by a significant alteration of the overall gut microbial ecology. This suggests that rifaximin can exert important eubiotic effects independently of the original disease, producing a favorable gut microbiota perturbation without changing its overall composition and diversity.

The use of biologic agents, particularly anti-tumor necrosis factor (TNF)-α, has revolutionized the treatment of inflammatory bowel diseases (IBD), modifying their natural history. Several data on the efficacy of these agents in inducing and maintaining clinical remission have been accumulated over the past two decades: their use avoid the need for steroids therapy, promote mucosal healing, reduce hospitalizations and surgeries and therefore dramatically improve the quality of life of IBD patients. However, primary non-response to these agents or loss of response over time mainly due to immunogenicity or treatment-related side-effects are a frequent concern in IBD patients. Thus, the identification of predicting factors of efficacy is crucial to allow clinicians to efficiently use these therapies, avoiding them when they are ineffective and eventually shifting towards alternative biological therapies with the end goal of optimizing the cost-effectiveness ratio. In this review, we aim to identify the predictive factors of short- and long-term benefits of anti-TNF-α therapy in IBD patients. In particular, multiple patient-, disease- and treatment-related factors have been evaluated.

The intestinal barrier serves 2 critical functions for the survival of the individual: first, it allows nutrient absorption and second, it defends the body from dangerous macromolecule penetration. It is a complex multilayer system, consisting of an external "anatomic" barrier and an inner "functional" immunological barrier. The interaction of these 2 barriers enables equilibrated permeability to be maintained. Many factors can alter this balance: gut microflora modifications, mucus layer alterations, and epithelial damage can increase intestinal permeability, allowing the translocation of luminal content to the inner layer of intestinal wall. Several techniques are now available that enable us to study gut permeability: "in vitro" models (Caco-2 and HT29-MTX cells) and "in vivo" not invasive tests (sugar tests and radioisotope scanning tests) are used to estimate permeability and to suggest molecular pathophysiological mechanisms of intestinal permeability in health and diseases. Many medicinal products used in the treatment of gastrointestinal diseases have also found to play an active role in modulate intestinal permeability: corticosteroids, 5-aminosalicylic acid, anti-tumor necrosis factor, probiotics, and mucosal protectors, like gelatin tannate. This review will particularly address the role of the gut barrier in maintaining intestinal permeability (microbiota, mucus, and epithelial cells), the techniques used for estimating intestinal permeability and the therapeutic approaches able to modify it.

Inflammatory bowel disease (IBD) patients have an increased risk of venous thromboembolism (VTE), which represents a significant cause of morbidity and mortality. The most common sites of VTE in IBD patients are the deep veins of the legs and pulmonary system, followed by the portal and mesenteric veins. However, other sites may also be involved, such as the cerebrovascular and retinal veins. The aetiology of VTE is multifactorial, including both inherited and acquired risk factors that, when simultaneously present, multiply the risk to the patient. VTE prevention involves correcting modifiable risk factors, such as disease activity, vitamin deficiency, dehydration and prolonged immobilisation. The role of mechanical and pharmacological prophylaxis against VTE using anticoagulants is also crucial. However, although guidelines recommend thromboprophylaxis for IBD patients, this method is still poorly implemented because of concerns about its safety and a lack of awareness of the magnitude of thrombotic risk in these patients. Further efforts are required to increase the rate of pharmacological prevention of VTE in IBD patients to avoid preventable morbidity and mortality.

Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial "fingerprint", characterized by the reduced ratio of "good" to "potentially pathogenic" bacteria has recently been outlined, and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover, in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and, portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic, immune-modulating and anti-inflammatory activity, a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE, and also to prevent the development of SBP, to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality, triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease.