Background & Aims: Escherichia coli Nissle 1917 (EcN) has been recommended as a therapeutic tool for ulcerative colitis (UC) treatment. However, to date, no meta-analysis has been performed on this topic. Methods: We performed a literature search on PubMed, MEDLINE, Science Direct and EMBASE. We evaluated success rates for induction of remission, relapse rates and side effects, expressed as Intention-To-Treat. Odd ratios (OR), pooled OR and 95% confidence intervals (CI) were calculated, based on the Mantel-Haenszel method. Heterogeneity was assessed by using the χ2 and I2 statistics and, if present, a random-effects model was adopted. Results: We selected six eligible trials, with 719 patients, 390 assigned to the study group and 329 to the control group. EcN induced remission in 61.6% of cases, while in the control group (mesalazine) the remission was achieved in 69.5% of cases, with a mean difference of 7.9%. The pooled OR was 0.92 (95% CI 0.15-9.66, p=0.93). A single study showed a better performance of EcN than the placebo. A relapse of the disease occurred in 36.8% in the EcN group and in 36.1% in the control group (mesalazine), with a mean difference of 0.8%, OR=1.07, with a 95% CI of 0.70-1.64 (p=0.74). Side effects were comparable (OR=1.44, 95% CI 0.80-2.59, p=0.22). Conclusions: EcN is equivalent to mesalazine in preventing disease relapse, thus confirming current guideline recommendations. EcN seems to be as effective as controls in inducing remission and therefore, its use cannot be recommended as in one study the comparison was performed against placebo. Further studies may be helpful for this subject. Abbreviations: EcN: Escherichia coli Nissle; UC: ulcerative colitis; IBD: inflammatory bowel disease; CD: Crohn’s disease; ITT: intention-to-treat.

Non celiac gluten sensitivity (NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease (CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as 'foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders (irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.

Nonalcoholic fatty liver disease (NAFLD) is common in inflammatory bowel diseases (IBD). Herein, NAFLD prevalence and risk factors in a large IBD cohort were evaluated and compared to that of a non-IBD sample. Crohn’s disease/ulcerative colitis outpatients referred to IBD service of our Gastroenterology Unit were enrolled. Subjects affected by functional and motor gastrointestinal disorders, in whom IBD was ruled out, referred to general outpatient service in the same area, were considered as nonIBD group. Exclusion criteria were based on previous diagnosis of nonNAFLD chronic liver diseases and secondary causes of fat liver overload. Characteristics of IBD and liver status were collected. Risk factors for metabolic syndrome were analyzed. Ultrasonographic presence and degree of steatosis were assessed. Data were examined by univariate and multivariate analyses. For this study 465 IBD and 189 non-IBD subjects were consecutively enrolled. NAFLD was found in 28.0% and 20.1% in IBD and non-IBD subjects, respectively (P = 0.04). IBD patients with NAFLD were younger than non-IBD ones. There was no significant difference in steatosis grade and association between NAFLD and IBD behavior, extension, activity, and drugs. In the IBD group, multivariate analysis demonstrated that NAFLD was independently associated to metabolic syndrome (OR=2.24, 95%CI 1.77–28.81), diabetes (OR=1.71, 95%CI 1.43–12.25), fasting blood glucose (OR=1.36, 95%CI 1.13–1.68), and abdominal circumference (OR=1.68, 95%CI 1.15–14.52). NAFLD is more common and occurs at a younger age in IBD than in nonIBD subjects. However, further investigation is required to ascertain possible NAFLD pathogenic IBD-related factors other than conventional/metabolic ones.

Inflammatory bowel disease (IBD) could be associated with several extra-intestinal manifestations (EIMs) involving musculoskeletal, hepatopancreatobiliary, ocular, renal, and pulmonary systems, as well as the skin. In the last years, hidradenitis suppurativa (HS) is acquiring an increasing interest. IBD, especially Crohn’s disease (CD), is among the most reported associated diseases in HS patients. The aim of this paper is to give a brief overview of data showing a possible epidemiologic and pathogenetic association between IBD and HS. We performed a pooled-data analysis of four studies and pooled prevalence of HS in IBD patients was 12.8%, with a 95%CI of 11.7%-13.9%. HS was present in 17.3% of subjects with CD (95%CI: 15.5%-19.1%) and in 8.5% of UC patients (95%CI: 7.0%-9.9%). Some items, especially altered immune imbalance, are generally involved in IBD pathogenesis as well as invoked by HS. Smoking is one of the most relevant risk factors for both disorders, representing a predictor of their severity, despite, actually, there being a lack of studies analyzing a possible shared pathway. A role for inheritance in HS and CD pathogenesis has been supposed. Despite a genetic susceptibility having been demonstrated for both diseases, further studies are needed to investigate a genetic mutual route. Although the pathogenesis of IBD and HS is generally linked to alterations of the immune response, recent findings suggest a role for intestinal and skin microbiota, respectively. In detail, the frequent finding of Staphylococcus aureus and coagulase-negative staphylococci on HS cutaneous lesions suggests a bacterial involvement in disease pathogenesis. Moreover, microflora varies in the different cutaneous regions of the body and, consequently, two different profiles of HS patients have been identified on these bases. On the other hand, it is well-known that intestinal microbiota may be considered as “the explosive mixture” at the origin of IBD despite the exact relationship having not been completely clarified yet. A better comprehension of the role that some bacterial species play in the IBD pathogenesis may be essential to develop appropriate management strategies in the near future. A final point is represented by some similarities in the therapeutic management of HS and IBD, since they may be controlled by immunomodulatory drugs. In conclusion, an unregulated inflammation may cause the lesions typical of both HS and IBD, particularly when they coexist. However, this is still a largely unexplored field.

Colorectal cancer (CRC) is one of the leading causes of mortality for cancer in industrialized countries. The link between diet and CRC is well-known, and presumably CRC is the type of cancer which is most influenced by dietary habits. In Western countries, an inadequate dietary intake of fibers is endemic, and this could be a driving factor in the increase of CRC incidence. Indeed, several epidemiologic studies have elucidated an inverse relationship between daily fiber intake and risk of CRC. Long-term prognosis in CRC survivors is also dependent on dietary fibers. Several pathogenetic mechanisms may be hypothesized. Fibers may interfere with the metabolism of bile acids, which may promote colon carcinogenesis. Further, fibers are often contained in vegetables which, in turn, contain large amounts of antioxidant agents like resveratrol, polyphenols, or phytoestrogens. Moreover, fibers can be digested by commensal flora, thus producing compounds such as butyrate, which exerts an antiproliferative effect. Finally, fibers may modulate gut microbiota, whose composition has shown to be associated with CRC onset. In this regard, dietary interventions based on high-fiber-containing diets are ongoing to prevent CRC development, especially in patients with high potential for this type of tumor. Despite the fact that outcomes are preliminary, encouraging results have been observed.