Gut--liver axis: the impact of gut microbiota on non alcoholic fatty liver disease.

AIM: To examine the impact of gut microbiota on non alcoholic fatty liver disease (NAFLD) pathogenesis. DATA SYNTHESIS: Emerging evidence suggests a strong interaction between gut microbiota and liver. Receiving approximately 70% of its blood supply from the intestine, the liver represents the first line of defence against gut-derived antigens. Intestinal bacteria play a key role in the maintenance of gut-liver axis health. Disturbances in the homeostasis between bacteria- and host-derived signals at the epithelial level lead to a break in intestinal barrier function and may foster "bacterial translocation", defined as the migration of bacteria or bacterial products from the intestinal lumen to mesenteric lymph nodes or other extraintestinal organs and sites. While the full repertoire of gut-derived microbial products that reach the liver in health and disease has yet to be explored, the levels of bacterial lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver diseases. Derangement of the gut flora, particularly small intestinal bacterial overgrowth, occurs in a large percentage (20-75%) of patients with chronic liver disease. In addition, evidence implicating the gut-liver axis in the pathogenesis of metabolic liver disorders has accumulated over the past ten years. CONCLUSIONS: Complex metabolic diseases are the product of multiple perturbations under the influence of triggering factors such as gut microbiota and diet, thus, modulation of the gut microbiota may represent a new way to treat or prevent NAFLD.

Risk factors in gastric cancer.

STATE OF THE ART: Gastric cancer (GC) is still a major health problem worldwide due to its frequency, poor prognosis and limited treatment options. At present prevention is likely to be the most effective means of reducing the incidence and mortality from this disease. The most important etiological factors implicated in gastric carcinogenesis are diet and Helicobacter pylori (H. pylori) infection. High intake of salted, pickled or smoked foods, as well as dried fish and meat and refined carbohydrates significantly increased the risk of developing GC while fibers, fresh vegetables and fruit were found to be inversely associated with GC risk. Epidemiological investigations (retrospective, case-control and prospective) and several meta-analyses have demonstrated that concurrent or previous H. pylori infection is associated with an increased risk of GC in respect to uninfected people. H. pylori colonizes gastric mucosa where it induces a complex inflammatory and immune reaction that on time leads to a severe mucosal damage i.e., atrophy, intestinal metaplasia (IM) and dysplasia. The risk of GC is closely related to the grade and extension of gastric atrophy, IM and dysplasia. PERSPECTIVES AND CONCLUSIONS: Today a plausible program for GC prevention means: (1) a correct dietary habit since childhood increasing vegetables and fruit intake, (2) a decrease of H. pylori spread improving family and community sanitation and hygiene, (3) a search and treat H. pylori strategy in offspring of GC, (4) a search and treat H. pylori strategy in patients with chronic atrophic gastritis and intestinal metaplasia (IM), (5) a careful endoscopic and histologic follow-up if precancerous lesions persist irrespective of H. pylori eradication.

Interleukin-13 mucosal production in Helicobacter pylori-related gastric diseases.

UNLABELLED: A shift from Th1 (IFN-gamma) towards Th2 (IL-4)-type immune response was found in patients with gastric cancer and dysplasia. Recently, IL-13 has been described as a central mediator of Th2-dominant immune response in different inflammatory diseases. AIM AND METHODS: to analyse, by Enzyme-Linked-Immuno-SPOT (ELISPOT) assay and immunohistochemistry, the IL-13 production of mononuclear cells obtained from gastric biopsies of 19 H. pylori-negative subjects and 23 H. pylori-positive patients. RESULTS: By ELISPOT, we did not find any significant variation of the spot range number of IL-13, IL-4 and IFN-gamma secreting cells, irrespective of H. pylori status. After antigenic exposition, the spot range for IL-13, IL-4 and IFN-gamma significantly increased (p<.0001) only in H. pylori-positive patients. A prevalent Th1 (IFN-gamma) immunoresponse was observed in 2/23 cases with active gastritis, while a prevalent Th2 (IL-13 and IL-4) was detected in 5/23 cases all with atrophic chronic gastritis of whom two with intestinal metaplasia. By immunohistochemistry, IL-13, IL-4 and IFN-gamma were detectable in all cases directly related to the inflammatory infiltrate. In the two cases with intestinal metaplasia, IL-13 and IL-4 were localised in both inflammatory and epithelial cells. This immunopattern was confirmed in selected additional 10 cases of H. pylori-positive chronic atrophic gastritis with intestinal metaplasia and 10 cases of intestinal type gastric cancer. CONCLUSION: These preliminary results suggest that IL-13 could be implicated in the different outcome of H. pylori infection.

Diagnostic accuracy of the serum profile of gastric mucosa in relation to histological and morphometric diagnosis of atrophy.

BACKGROUND: Histology is the gold standard for diagnosis of atrophy but is hampered by observer variation. A reliable method to overcome this issue is morphometric analysis of gastric mucosa. Serum pepsinogens and gastrin have been proposed in the diagnostic work-up of gastric atrophy although diagnostic accuracy of these tests is considered unsatisfactory. AIM: To evaluate the diagnostic accuracy of gastric serum profile in relation both to morphological and morphometric diagnosis of gastric atrophy. METHODS: Ninety-four dyspeptic out-patients underwent upper endoscopy and evaluation of serum levels of PGI, PGII and 17-gastrin. Diagnostic accuracy of gastric serum profile was tested by receiver operating characteristic curves and by evaluation of sensitivity and specificity in relation to both histology and morphometric analyses. RESULTS: As far as concern to histological evaluation, only PGI/PGII ratio showed an acceptable diagnostic accuracy in discrimination of gastric atrophy, while, when morphometric analysis was considered as reference, both serum PGI level and PGI/PGII ratio showed an excellent performance. However, both PGI and PGI/PGII ratio showed low sensitivity and high specificity. CONCLUSIONS: Serological gastric profile corresponds better with the morphometric diagnosis of atrophy, even if, because of the low sensitivity, today this could only be used as screening test of chronic atrophic gastritis.

The role of gut microbiota in the pathogenesis and management of allergic diseases.

Allergy is defined as a hypersensitivity reaction due to specific antibody-mediated or cell-mediated immunologic mechanisms. Epidemiological studies are showing a dramatic increase of allergies in industrialized countries in the last few decades, while remaining stable in developing countries. In 1989 Strachan, hypothesized that the increase in allergic disorders was the result of a lack of infections in early infancy, and in 1998 Wold suggested that, rather than a decrease in viral or bacterial infections, an altered normal intestinal colonization pattern in infancy, could be responsible for the increase in allergies. Germ-free mice were shown to mount an exaggerated allergic airway reaction compared with that seen in colonized mice, indicating the important role of microbe-host interactions in the development of allergic diseases. Infants with food allergies are found to exhibit an imbalance between "beneficial"and potentially harmful bacteria, i.e., decreased Lactobacilli, Bifidobacteria and Enterococcus species and increased coliforms, Staphylococcus aureus and Clostridium species, suggesting that microbial inhabitants of the human body, may play either a pathogenic or protective role in allergies. Based on this data, many clinical trial addressing the use of probiotics in the context of allergic disorders, have been conducted in children. However, currently, no conclusive item may be drawn.

Tissue ghrelin level and gastric emptying rate in adult patients with celiac disease.

Celiac disease (CD) patients show a number of gastrointestinal motor abnormalities. Ghrelin, a gastric peptide implicated in short-term feeding control and long-term body weight regulation, has been recently considered a key regulator of gastric motility. The aim of this study was to evaluate the gastric emptying rate of solids and the density of ghrelin-immunopositive cells in adult CD patients before and at least 1 year after starting a gluten-free diet. Twenty CD patients (M 8/F 12; mean age 36 years) and 10 controls underwent endoscopy with gastric and duodenal biopsies and 13C-octanoic acid breath test to measure gastric emptying of solids. Celiac disease patients repeated the protocol at least 1 year after starting gluten-free diet. Ghrelin tissue levels were evaluated by immunohistochemistry on gastric mucosa specimens. Gastric emptying time was normal in all control subjects (t(1/2) = 89 +/- 16 min) while it was delayed in CD patients prior to gluten-free diet (t(1/2) = 252 +/- 101 min; P < 0.005). The mean number of ghrelin-positive cells/field (x 400) was 14.4 +/- 2.7 in controls and 25.3 +/- 5.7 in CD patients respectively (P < 0.0001). Gluten withdrawal was effective in normalizing gastric emptying time in all CD patients (97 +/- 14 min; P < 0.0001) and resulted in a significant reduction of the density of ghrelin-immunopositive cells (19.8 +/- 5.4; P < 0.0001). The density of ghrelin-positive cells correlated directly with the degree of duodenal damage (P < 0.001) and inversely with the body mass index of CD patients (P < 0.0001). However, in neither CD patients nor controls, a correlation between tissue ghrelin levels and gastric emptying rate was detected. In conclusion, tissue ghrelin level does not correlate with gastric emptying rate in adult CD patients and in controls.