The role played by the gut in nonalcoholic fatty liver disease (NAFLD) is still a matter of debate, although animal and human studies suggest that gut-derived endotoxin may be important. We investigated intestinal permeability in patients with NAFLD and evaluated the correlations between this phenomenon and the stage of the disease, the integrity of tight junctions within the small intestine, and prevalence of small intestinal bacterial overgrowth (SIBO). We examined 35 consecutive patients with biopsy-proven NAFLD, 27 with untreated celiac disease (as a model of intestinal hyperpermeability) and 24 healthy volunteers. We assessed the presence of SIBO by glucose breath testing (GBT), intestinal permeability by means of urinary excretion of ⁵¹Cr-ethylene diamine tetraacetate (⁵¹Cr-EDTA) test, and the integrity of tight junctions within the gut by immunohistochemical analysis of zona occludens-1 (ZO-1) expression in duodenal biopsy specimens. Patients with NAFLD had significantly increased gut permeability (compared with healthy subjects; P < 0.001) and a higher prevalence of SIBO, although both were lower than in the untreated celiac patients. In patients with NAFLD, both gut permeability and the prevalence of SIBO correlated with the severity of steatosis but not with presence of NASH. Conclusions: Our results provide the first evidence that NAFLD in humans is associated with increased gut permeability and that this abnormality is related to the increased prevalence of SIBO in these patients. The increased permeability appears to be caused by disruption of intercellular tight junctions in the intestine, and it may play an important role in the pathogenesis of hepatic fat deposition. (HEPATOLOGY 2009.)

Familial Mediterranean Fever (FMF), an autosomal recessive disorder, is characterised by recurrent attacks of fever and serositis, lasting 24-72 hours. Since 1972 colchicine has become the drug of choice for prophylaxis against FMF attacks and amyloidosis FMF-associated. Colchicine, an alkaloid neutral, is absorbed in the jejunum and ileum. It metabolised by liver and only small amounts are recovered unchanged in the urine. Really plasma half-life is prolonged in patients with liver or renal failure. Colchicine is able to prevent activation of neutrophils, binding β-tubulin and making β-tubulin-colchicine complexes; this way inhibits assembly of microtubules and mitotic spindle formation; moreover its mode of action includes modulation of chemokines, prostanoids production, inhibition of neutrophil and endothelial cell adhesion molecules. The minimal daily dose in adults is 1.0 mg / die, but in children there is not a definite dose. Since in vitro high dosages of colchicine stop mitosis, this drug might interfere with male and female fertility and with children growth, but, according to current guidelines and because of rare side effects of the drug, FMF patients are recommended to take colchicine. Since colchicine treatment is often complicated by frequent gastrointestinal side effects, by our experience, in order to improve colchicine tolerance we recommend: lactose-free diet and treatment of intestinal bacterial overgrowth and / or Hp-infection, assessed by breath tests. Since our data showed that 10-15% of FMF patients seem are non-responders or intolerant to colchicine, today we are working in the design of colchicine analogues which may have lesser toxicities and a larger therapeutic window.

Management and treatment of lactose malabsorption

Background The onset of a sprue‐like enteropathy in association with olmesartan therapy has been recently reported. Aims To perform a systematic review of the literature and describe three additional cases of olmesartan‐associated enteropathy. Methods Electronic and manual bibliographic searches were performed to identify original reports in which subjects who were undertaking olmesartan developed a sprue‐like enteropathy. Because of the scarcity of studies with adequate sample size, case series with less than 10 patients and case reports were also considered. Data extraction was performed independently by two reviewers. Results A total of 11 publications met our pre‐defined inclusion criteria, for an overall number of 54 patients (including our series). Almost all patients presented with diarrhoea and weight loss. Normocytic normochromic anaemia and hypoalbuminaemia were the commonest laboratory defects at presentation. Antibody testing for coeliac disease was always negative. Variable degrees of duodenal villous atrophy were present in 98% of patients, while increased intra‐epithelial lymphocytes were documented in only 65% of cases. After discontinuation of olmesartan, all reported patients achieved resolution of signs and symptoms. Conclusions Although the available evidence is limited, the olmesartan‐associated sprue‐like enteropathy may be considered as a distinct clinical entity, and should be included in the differential diagnosis when serological testing for coeliac disease is negative.

Autoimmune enteropathy is a rare disorder characterized by severe and protracted diarrhea, weight loss from malabsorption and immune-mediated damage to the intestinal mucosa, generally occurring in infants and young children, although some cases of adult onset have been reported in the literature. Pathogenetic mechanisms involve immunological disorders, in which the presence of antienterocyte autoantibodies, although detected since first description, seems now to be secondary. As occurs frequently in autoimmunity, subjects with autoimmune enteropathy may be affected by other autoimmune disorders, sometimes leading to particular forms, i.e. the IPEX syndrome and the APECED syndrome. The prognosis of autoimmune enteropathy patients depends on the severity of digestive symptoms (including fecal output), on the severity and extension of histological lesions along the gastrointestinal apparatus, and on the presence of extra-intestinal involvement. Management of autoimmune enteropathy patients is based on nutritional support and adequate hydration to ensure optimal growth and development, together with immunosuppressive therapy. Recently, biological agents have been introduced, with apparent beneficial effects.

Background/Aims: Lactobacilli are used in the prevention and treatment of several diseases, but they are also known to play a role in the pathogenesis of dental caries. The aim of our study was to evaluate whether the oral administration of lactobacilli could change the salivary counts of these bacteria compared with placebo. Moreover, lactobacilli were administered in liquid and in capsule form to determine the role of direct contact with the oral cavity. Methods: Thirty-five healthy volunteers were randomized into three groups to receive lactobacilli and/or placebo for 45 days: group A (n = 14) received probiotics in capsules and placebo in liquid form; group B (n = 16) took liquid probiotics and placebo in capsules, and group C (n = 5) used placebo in both liquid and capsule form. Streptococcus mutans populations served as control. The salivary counts of lactobacilli and S. mutans were measured semi-quantitatively using the CRT® bacteria kit. Results: Compared with placebo, the oral administration of probiotics, both in capsules and in liquid form, significantly increases salivary counts of lactobacilli (p = 0.005 and p = 0.02, respectively). S. mutans populations were not significantly modified. Conclusions: The increased salivary counts of lactobacilli may indicate the need to closely monitor the dental health of patients undergoing long-term probiotics treatment, even when this treatment is administrated in a form that avoids direct contact with the oral cavity.