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... adequately deal with such peptides, a group of specific peptidases is necessary [43]. Initially, the proline specific peptidase and general aminopeptidase activities of VSL#3 were characterized by using synthetic substrates relatively specific for proline iminopeptidase, aminopeptidase type N and A, dipeptidase, prolinase, prolidase, dipeptidyl peptidase, tripeptidase, prolyl- endopeptidase and endopeptidase enzymes (Table 1). All these enzyme activities were found in the VSL#3 prepara- tion. ...
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Celiac disease (CD) is an autoimmune enteropathy caused by an abnormal immune response to gliadin peptides in genetically predisposed individuals. For people with CD, the only available therapy thus far is the lifelong necessity for a gluten-free diet (GFD). Innovative therapies include probiotics and postbiotics as dietary supplements, both of whi...
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... In this way, there is a greater translocation of the gliadin peptides to the lamina propria [44,45]. De Simone formulation [46], a probiotic preparation composed mainly by Lactobacilli and Bifidobacteria, not only hydrolyzed the epitopes 62-75 and the peptide 33-MER derived from gliadin, but also improved the epithelial barrier function by stabilizing the tight junctions, through the modulation of zonulin [47]. In fact, zonulin appears to be partly responsible for the increased intestinal permeability, linked to the disassembly of tight junctions, which characterizes the initial phase of CD [48]. ...
Celiac disease (CD) is an immune-mediated enteropathy correlated to the gluten ingestion in genetically predisposed subjects. The current and only therapy is a Gluten Free Diet (GFD). In recent years, new therapies and complementary strategies are being studied, including the modulation of the intestinal microbiome. The gut microbiota is involved in the onset and perpetuation of intestinal inflammation of various chronic bowel diseases, including CD. Intestinal dysbiosis has been reported in not treated or treated (with the GFD) celiac individuals, compared to healthy ones. Numerous studies have identified different bacterial clusters associated with CD. However, it's still unclear whether gut dysbiosis is the cause or effect of CD.
... Since the last decade, several studies [80][81][82][83] have been carried out aiming at showing the capacity of proteolytic enzymes, mainly peptidases, of selected sourdough lactobacilli to degrade gluten during food processing. The use of pooled cell suspensions and cell-free extracts obtained by different lactic acid bacteria strains was investigated [84]. ...
... The use of pooled cell suspensions and cell-free extracts obtained by different lactic acid bacteria strains was investigated [84]. Although a number of in vitro (e.g., agglutination and Caco-2/TC assays), ex vivo (biopsy-derived T cells), and acute in vivo (intestinal permeability) tests were carried out, the above results [80][81][82][83] only showed a marked decrease of the gliadin fraction, but not a complete degradation. Recently, it was shown that a traditional sourdough fermentation, leading to a partial gluten hydrolysis of wheat flour proteins, is not able to prevent the interaction of transglutaminase 2 with α2-gliadin or gluten; thus it cannot be considered safe for making GF products [85]. ...
Sourdough fermentation, a traditional biotechnology for making leavened baked goods, was almost completely replaced by the use of baker’s yeast and chemical leavening agents in the last century. Recently, it has been rediscovered by the scientific community, consumers, and producers, thanks to several effects on organoleptic, technological, nutritional, and functional features of cereal-based products. Acidification, proteolysis, and activation of endogenous enzymes cause several changes during sourdough fermentation, carried out by lactic acid bacteria and yeasts, which positively affect the overall quality of the baked goods. In particular, the hydrolysis of native proteins of the cereal flours may improve the functional features of baked goods. The wheat flour processed with fungal proteases and selected lactic acid bacteria was demonstrated to be safe for coeliac patients. This review article focuses on the biotechnologies that use selected sourdough lactic acid bacteria to potentially counteract the adverse reactions to gluten, and the risk of gluten contamination.
... The aim of this study was to examine the effects of a probiotic supplement on the CoeD microbiota. We selected the multispecies probiotic VSL#3 which has been found to hydrolyse gliadin polypeptides and reduce the toxic properties of wheat flour and was superior to other commercial available multistrain probiotics [16]. VSL#3 has also been shown to promote and maintain remission and alter the microbiota of individuals with other gastrointestinal pathologies including ulcerative colitis and pouchitis [17, 18] and stimulate the expression of the " house-keeping " molecules transforming growth factor beta-1 (TGFí µí»½-1) and claudin-2 in Caco-2 cells which are involved in mucosal protection [19]. ...
Background . There is limited research investigating the composition of the gastrointestinal microbiota in individuals with celiac disease (CoeD) reporting only partial symptom improvement despite adherence to a strict gluten-free diet (GFD). The aim of this research was to determine if the gastrointestinal microbiota could be altered by probiotic bacteria and provide a potential new therapy for this subgroup. Methods . A multicentre RCT was conducted between January and August 2011 in Australia. Participants included 45 people with CoeD reporting only partial symptom improvement despite adherence to a strict GFD for a minimum of 12 months. Participants took 5 g of VSL# ™ probiotic formulation ( n = 23 ) or 5 g placebo ( n = 22 ) orally twice daily for 12 weeks. The main outcome measured was the efficacy of the probiotic formula in altering faecal microbiota counts between baseline and week 12. Safety was determined by safety blood and monitoring adverse events. Results . SPSS ™ multivariate repeated measures analysis (95th confidence level) revealed no statistically significant changes between the groups in the faecal microbiota counts or blood safety measures over the course of the study. Conclusion . The probiotic formula when taken orally over the 12-week period did not significantly alter the microbiota measured in this population. The trial was registered with Australian and New Zealand Clinical Trials Register ACTRN12610000630011 .
... De Angelis (2006) aimed at showing the capacity of probiotic VSL#3 preparation (10 9 CFU/ml) to hydrolyse extensively wheat flour gliadins as a tool for decreasing the level of toxic or immunogenic epitopes causing celiac disease. Two-dimensional electrophoresis, immunological (R5 antibody), and mass spectrometry analyses showed an almost complete degradation of gliadin during long-time fermentation of wheat flour by VSL#3. ...
Food allergy is an adverse immune response to some proteins in some foods. Probiotic, health promoting bacteria have gained much importance because of their innumerable benefits, particularly in the treatment of diarrhea, hypercholesterolemia, atopic dermatitis, eczema, and gastrointestinal disorders by strengthening the immune system. The current paper reviews recent advances made in the treatment of food allergy through employing probiotic or synbiotic therapy. The results of several reports are very promising suggesting probiotics can influence the immune system to curtail the allergic responses.
... For instance, such studies could be performed with VSL#3® (Sigma-Tau Pharmaceuticals, Gaithersburg, MD, USA), a commercially available probiotic product that contains four different bifidobacteria and Lactobacillus species that hydrolyse gliadin. 42 ...
Coeliac disease is a common and fairly well-characterized systemic disorder that mainly affects the small intestine, but also has extraintestinal manifestations. The environmental trigger (gluten derived from wheat, rye and barley), the genetic predisposition conferred by the HLA-DQ2 and HLA-DQ8 haplotypes and many steps in the disease pathogenesis are known. This knowledge has enabled researchers to suggest novel alternative treatments or adjunctive therapies to the gluten-free diet, which is currently the only available and effective treatment for the condition. This Review focuses on emerging and potential treatment strategies that are based on the current concept of the disease pathophysiology. The search for novel future treatment modes, including nonpharmacological and pharmacological approaches, is also outlined. The potential pitfalls associated with the various research avenues are also discussed.
... The large proportion and location of proline (P) residues in these toxic peptides make them extremely resistant to proteolysis ( Stepniak et al., 2006), thus specific peptidases are necessary to hydrolyze the cyclic structure of P ( Hausch et al., 2002). The proteolytic system of lactic acid bacteria (LAB) of sourdough origin has been subjected to several studies from a nutritional and technological standpoint, where the ability of LAB to hydrolyze a-gliadin-fragments is in a relevant place ( De Angelis et al., 2005;Sollid and Khosla, 2005;Rollán et al., 2005;Gerez et al., 2008). In a previous study, several lactobacilli and pediococci were tested for the ability to hydrolyze the 31e43, 62e75, and 57e89 (33 mer) a-gliadin fragments; the latter one was only degraded (56.6%) by the pool Lactobacillus plantarum CRL 775/ Pediococcus pentosaceus CRL 792 ( Gerez et al., 2008). ...
... In line with this concept, different probiotic bacterial strains have been tested. Among probiotic preparations, VSL#3, a highly concentrated mixture of lactic acid and bifidobacteria , was able to hydrolyze completely the α2-gliadin- derived epitopes 62–75 and 33 mer (750 ppm) [57]. It is interesting to underline that probiotics, defined as the viable microorganisms that exhibit a beneficial effect on the health of the host by improving its intestinal microbial balance, could directly modulate the function of epithelial cells. ...
... It is interesting to underline that probiotics, defined as the viable microorganisms that exhibit a beneficial effect on the health of the host by improving its intestinal microbial balance, could directly modulate the function of epithelial cells. It has been reported that different probiotic strains, including the VSL3# preparation, increase epithelial barrier function by stabilizing tight junctions and inducing mucin secretion in epithelial cells [57, 58]. Furthermore, several probiotic bacterial strains are able to protect the epithelium , presumably by the aforementioned mechanisms, from various insults, including pathogenic bacteria [59, 60] and inflammatory cytokines [61, 62]. ...
Celiac disease is a permanent intolerance to the gliadin fraction of wheat gluten and to similar barley and rye proteins that occurs in genetically susceptible subjects. After ingestion, degraded gluten proteins reach the small intestine and trigger an inappropriate T cell-mediated immune response, which can result in intestinal mucosal inflammation and extraintestinal manifestations. To date, no pharmacological treatment is available to gluten-intolerant patients, and a strict, life-long gluten-free diet is the only safe and efficient treatment available. Inevitably, this may produce considerable psychological, emotional, and economic stress. Therefore, the scientific community is very interested in establishing alternative or adjunctive treatments. Attractive and novel forms of therapy include strategies to eliminate detrimental gluten peptides from the celiac diet so that the immunogenic effect of the gluten epitopes can be neutralized, as well as strategies to block the gluten-induced inflammatory response. In the present paper, we review recent developments in the use of enzymes as additives or as processing aids in the food biotechnology industry to detoxify gluten.
... No hydrolysis of the proline-rich 33-mer epitope was found when it was treated with PepX alone. When the general aminopeptidase type N from the same bacterium was combined with PepX, the hydrolysis of the 33-mer peptide (0.2 mmol/L) was complete after 24 hours of incubation at 30 C. In conclusion, these studies (Di Cagno et al., 2004;De Angelis et al., 2005;Gallo et al., AU2 2005) show that selected sourdough or probiotic lactic acid bacteria may possess a Each value is the average of three enzyme assays, and standard deviations were calculated. b Aliquots (25 L) of each cell suspension were used in the enzyme assays. ...
... The same approach as that described for sourdough wheat bread (Di Cagno et al., 2004;De Angelis et al., 2005) was adapted for pasta-making. A pool of selected lactic acid bacteria was used to ferment durum wheat semolina under liquid conditions . ...
... Although a number of in vitro (e.g. agglutination and Caco-2/TC assays), ex vivo (biopsy-derived T cells) and acute in vivo (intestinal permeability) tests were carried out, the above results (Di Cagno et al., 2004, 2005De Angelis et al., 2005 only showed a marked decrease of the gliadin fraction. This route might be helpful to eliminate the risk of cross-contamination of gluten-free products but not to completely eliminate the toxicity of wheat flour. ...
The use of sourdough as the natural starter for leavening is one of the oldest biotechnological processes in food fermentation. Sourdough is a mixture of flour (e.g. wheat, rye), water, and other ingredients that is fermented by naturally occurring lactic acid bacteria and yeasts. Although these microorganisms originate mainly from flours and process equipment, the resulting composition of the sourdough microbiota is determined by endogenous and exogenous factors. In the mature sourdoughs, lactic acid bacteria dominate, occurring in numbers > 108 cfu/g, whereas the number of yeasts is orders of magnitude lower. Three standard protocols are distinguished for sourdough fermentation. Type I sourdough is manufactured with a traditional technique and is characterized by continuous, daily refreshments to maintain the microorganisms in an active state, as indicated by their high metabolic activity. The process is carried out at room temperature (20-30°C) and the final pH of the sourdough is ca. 4.0. Type II sourdough is used as dough acidifier. The fermentation lasts 2-5 days at >30°C to speed up the process and the pH is <3.5 after 24 hours of fermentation. The microorganisms are in the late stationary phase of growth and exhibit restricted metabolic activity. Type III is a dried sourdough in powder form that is fermented by defined starter cultures. It is used as acidifier supplement and aroma carrier during breadmaking.
... Another conceivable mode of action for B. lactis is that they modulate directly the function of epithelial cells. It has been reported that different probiotic strains, including the VSL3# preparation, probiotic bacterial lysates or conditioned medium increase epithelial barrier function as measured with TER252627 . In addition, at least some probiotics stabilize tight junctions and induce mucin secretion in epithelial cells [25] . ...
... It has been reported that different probiotic strains, including the VSL3# preparation, probiotic bacterial lysates or conditioned medium increase epithelial barrier function as measured with TER252627 . In addition, at least some probiotics stabilize tight junctions and induce mucin secretion in epithelial cells [25] . Furthermore, several probiotic bacterial strains have proved able to protect the epithelium, presumably by the above-mentioned mechanisms, from various insults including pathogenic bacteria [25,28] and inflammatory cytokines [29,30]. ...
... In addition, at least some probiotics stabilize tight junctions and induce mucin secretion in epithelial cells [25] . Furthermore, several probiotic bacterial strains have proved able to protect the epithelium, presumably by the above-mentioned mechanisms, from various insults including pathogenic bacteria [25,28] and inflammatory cytokines [29,30]. Thus B. lactis might protect the epithelium from the insult caused by gliadin by direct action on the cells. ...
Wheat gliadin induces severe intestinal symptoms and small-bowel mucosal damage in coeliac disease patients. At present, the only effective treatment for the disease is a strict life-long gluten-free diet. In this study we investigated whether probiotics Lactobacillus fermentum or Bifidobacterium lactis can inhibit the toxic effects of gliadin in intestinal cell culture conditions. The ability of live probiotics to inhibit peptic-tryptic digested gliadin-induced damage to human colon cells Caco-2 was evaluated by measuring epithelial permeability by transepithelial resistance, actin cytoskeleton arrangements by the extent of membrane ruffling and expression of tight junctional protein ZO-1. B. lactis inhibited the gliadin-induced increase dose-dependently in epithelial permeability, higher concentrations completely abolishing the gliadin-induced decrease in transepithelial resistance. The same bacterial strain also inhibited the formation of membrane ruffles in Caco-2 cells induced by gliadin administration. Furthermore, it also protected the tight junctions of Caco-2 cells against the effects of gliadin, as evinced by the pattern of ZO-1 expression. We conclude thus that live B. lactis bacteria can counteract directly the harmful effects exerted by coeliac-toxic gliadin and would clearly warrant further studies of its potential as a novel dietary supplement in the treatment of coeliac disease.
... 450 billion cells/sachet), containing Streptococcus thermophilus, Lb. plantarum, Lb. acidophilus, Lactobacillus casei, Lactobacillus delbrueckii spp. bulgaricus, Bifidobacterium breve, Bifidobacterium longum and Bifidobacterium infantis (De Angelis et al., 2006b). For the above reasons, sourdough fermentation is a representative of traditional biotechnology of outstanding importance with great potential in human diet. ...
Sourdough technology is widely used; it is employed in bread making and for the production of cakes. Sourdough is characterized by a complex microbial ecosystem, mainly represented by lactic acid bacteria and yeasts, whose fermentation confers to the resulting bread its characteristic features such as palatability and high sensory quality. Investigation of the microbial composition of sourdough is relevant in order to determine the potential activities of sourdough microorganisms. This review focuses on the role of the most important group of sourdough fermenting bacteria that consists of lactobacilli; species that belong to the Lactobacillus genus are the main responsible of flavor development, improvement of nutritional quality as well as stability over consecutive refreshments of sourdough. Lactobacilli also establish some durable microbial associations. An overview of the tools for monitoring predominant species is also reported.
