Oral administration of antigens from intestinal flora anaerobic bacteria reduces the severity of experimental acute colitis in BALB/c mice.

Homeostasis between indigenous intestinal flora and host response may be broken in inflammatory bowel disease. The present study explores whether repeated oral administration of intestinal flora antigens can protect mice against dextran sodium sulphate (DSS)-induced colitis. Sonicates of Gram-positive, Gram-negative, or anaerobic resident bacteria isolated from mouse intestinal flora were fed to BALB/c mice by gastric gavage, with or without cholera toxin. After four weekly doses of 1 mg of these antigen preparations (or of PBS as control), DSS colitis was induced. One week later colitis was evaluated by clinical scores and histology. Mice fed a pool of the three sonicates had decreased inflammation scores (5 (1-14); median (range)) compared with PBS-fed control animals (15 (7-19); P < 0.05). Decreased inflammation was observed in mice fed anaerobic bacteria antigens (7 (6-11); P < 0.05 versus control), but not in mice fed a pool of Gram-positive and -negative sonicates (16 (12-16)). Inflammation scores of mice fed antigens with cholera toxin were similar to those of PBS-fed control animals. DSS-induced colitis can be suppressed by oral administration of normal intestinal flora antigens containing anaerobes.

The gut as a lymphoepithelial organ: the role of intestinal epithelial cells in mucosal immunity.

Mucosal surfaces covered by a layer of epithelial cells represent the largest and most critical interface between the organism and its environment. The barrier function of mucosal surfaces is performed by the epithelial layer and immune cells present in the mucosal compartment. As recently found, epithelial cells, apart from their participation in absorptive, digestive and secretory processes perform more than a passive barrier function and are directly involved in immune processes. Besides the well known role of epithelial cells in the transfer of polymeric immunoglobulins produced by lamina propria B lymphocytes to the luminal content of mucosals (secretory Igs), these cells were found to perform various other immunological functions, to interact with other cells of the immune system and to induce an efficient inflammatory response to microbial invasion: enzymic processing of dietary antigens, expression of class I and II MHC antigens, presentation of antigens to lymphocytes, expression of adhesive molecules mediating interaction with intraepithelial lymphocytes and components of extracellular matrix, production of cytokines and probable participation in extrathymic T cell development of intraepithelial lymphocytes. All these functions were suggested to influence substantially the mucosal immune system and its response. Under immunopathological conditions, e.g. during infections and inflammatory bowel and celiac diseases, both epithelial cells and intraepithelial lymphocytes participate substantially in inflammatory reactions. Moreover, enterocytes could become a target of mucosal immune factors. Mucosal immunosurveillance function is of crucial importance in various pathological conditions but especially in the case of the most frequent malignity occurring in the intestinal compartment, i.e. colorectal carcinoma. Proper understanding of the differentiation processes and functions of epithelial cells in interaction with other components of the mucosal immune system is therefore highly desirable.

Binding of gliadin to lymphoblastoid, myeloid and epithelial cell lines.

The aim of our work was to investigate the in vitro reactivity of gliadin peptides of natural and synthetic origin with various cell lines. We have found that all tested cell lines of human, mouse and rat origin were agglutinated by enzymically digested gliadin (peptic-tryptic- and peptic-tryptic pancreatic digest of alpha-gliadin) in a concentration dependent manner. In order to test the specificity of binding, inhibition studies were performed using a panel of sugars as well as natural and synthetic peptides derived from gliadin. We have found that among twelve tested sugars only fetuin and phosphomannan were able to inhibit the agglutination of K562 cells with peptic-tryptic- but not with peptic-tryptic pancreatic digest of alpha-gliadin. The lack of inhibition by gliadin peptides and most of the saccharides suggests that agglutinating activity of gliadin is the result of a nonspecific binding of gliadin to the cell membrane.

Study of behavior of rats with gluten-induced enteropathy

Association of different psychological and neurological disturbances with gluten intake in coeliac patients was repeatedly described. In the present study gluten-induced enteropathy was elicited in rats by prolonged intragastric administration of gliadin from birth to 10 weeks. Various neurological (contact and visual placing reactions, equilibrium on horizontal bar) and behavioral tests (open field and Morris water maze task) were used to assess the possible deficits. No substantial differences were found in the behavior of rats fed with gliadin compared with those fed with bovine serum albumin (control group). The only difference found between control and experimental rats was that gliadin-fed rats showed slightly higher emotionality in the open field test. It is concluded that prolonged application of gliadin to young rats at enteropathy-inducing dosages does not modify their behavior

Study of behavior of rats with gluten-induced enteropathy

Association of different psychological and neurological disturbances with gluten intake in coeliac patients was repeatedly described. In the present study gluten-induced enteropathy was elicited in rats by prolonged intragastric administration of gliadin from birth to 10 weeks. Various neurological (contact and visual placing reactions, equilibrium on horizontal bar) and behavioral tests (open field and Morris water maze task) were used to assess the possible deficits. No substantial differences were found in the behavior of rats fed with gliadin compared with those fed with bovine serum albumin (control group). The only difference found between control and experimental rats was that gliadin-fed rats showed slightly higher emotionality in the open field test. It is concluded that prolonged application of gliadin to young rats at enteropathy-inducing dosages does not modify their behavior (AU)