1.
Leaky gut - concept or clinical entity?
Quigley, EM
Current opinion in gastroenterology. 2016;(2):74-9
Abstract
PURPOSE OF REVIEW This article evaluates the current status of the gut barrier in gastrointestinal disorders. RECENT FINDINGS The gut barrier is a complex, multicomponent, interactive, and bidirectional entity that includes, but is not restricted to, the epithelial cell layer. Intestinal permeability, the phenomenon most readily and commonly studied, reflects just one (albeit an important one) function of the barrier that is intimately related to and interacts with luminal contents, including the microbiota. The mucosal immune response also influences barrier integrity; effects of inflammation per se must be accounted for in the interpretation of permeability studies in disease states. SUMMARY Although several aspects of barrier function can be assessed in man, one must be aware of exactly what a given test measures, as well as of its limitations. The temptation to employ results from a test of paracellular flux to imply a role for barrier dysfunction in disorders thought to be based on bacterial or macromolecular translocation must be resisted. Although changes in barrier function have been described in several gastrointestinal disorders, their primacy remains to be defined. At present, few studies support efficacy for an intervention that improves barrier function in altering the natural history of a disease process.
2.
Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model.
de Barros, JM, Costabile, A, Charalampopoulos, D, Khutoryanskiy, VV, Edwards, AD
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2016;:115-22
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Abstract
Gastrointestinal (GI) models that mimic physiological conditions in vitro are important tools for developing and optimizing biopharmaceutical formulations. Oral administration of live attenuated bacterial vaccines (LBV) can safely and effectively promote mucosal immunity but new formulations are required that provide controlled release of optimal numbers of viable bacterial cells, which must survive gastrointestinal transit overcoming various antimicrobial barriers. Here, we use a gastro-small intestine gut model of human GI conditions to study the survival and release kinetics of two oral LBV formulations: the licensed typhoid fever vaccine Vivotif comprising enteric coated capsules; and an experimental formulation of the model vaccine Salmonella Typhimurium SL3261 dried directly onto cast enteric polymer films and laminated to form a polymer film laminate (PFL). Neither formulation released significant numbers of viable cells when tested in the complete gastro-small intestine model. The poor performance in delivering viable cells could be attributed to a combination of acid and bile toxicity plus incomplete release of cells for Vivotif capsules, and to bile toxicity alone for PFL. To achieve effective protection from intestinal bile in addition to effective acid resistance, bile adsorbent resins were incorporated into the PFL to produce a new formulation, termed BR-PFL. Efficient and complete release of 4.4×10(7) live cells per dose was achieved from BR-PFL at distal intestinal pH, with release kinetics controlled by the composition of the enteric polymer film, and no loss in viability observed in any stage of the GI model. Use of this in vitro GI model thereby allowed rational design of an oral LBV formulation to maximize viable cell release.
3.
The aging/precancerous gastric mucosa: a pilot nutraceutical trial.
Marotta, F, Barreto, R, Tajiri, H, Bertuccelli, J, Safran, P, Yoshida, C, Fesce, E
Annals of the New York Academy of Sciences. 2004;:195-9
Abstract
The aim of this study was to test the effect of antioxidant supplementation on enzymatic abnormalities and free radical-modified DNA adducts associated with premalignant changes in the gastric mucosa of elderly patients with HP-negative atrophic gastritis (CAG). Sixty patients with atrophic gastritis and intestinal metaplasia underwent a nutritional interview and a gastroscopy with multiple biopsy samples in the antrum that were processed for histology and for assaying: alpha-tocopherol, MDA, xanthine oxidase (XO), ornithine decarboxylase (ODC), and 8-OHdG. Patients were randomly allocated into three matched groups and supplemented for 6 months with (1) vitamin E, 300 mg/day; (2) multivitamin, two tablets t.i.d.; and (3) Immun-Age 6 g/day nocte (ORI, Gifu, Japan), a certified fermented papaya preparation with basic science-validated antioxidant/immunomodulant properties. Ten dyspeptic patients served as controls. Histology and biochemistry were blindly repeated at 3 and 6 months. CAG patients showed a significantly (P <.05) increased level of mucosal MDA and XO concentration that were reverted to normal by each supplementation (P <.05). All supplements caused a significant decrease of ODC (P <.01), but Immun-Age yielded the most effective (P < 0.05) and was the only one significantly decreasing 8-OhdG (P < 0.05). These data suggest that antioxidant supplementation, and, namely, Immun-Age, might be potential chemopreventive agents in HP-eradicated CAG patients and especially in the elderly population.