National Institute For Digestive Diseases Irccs Saverio Of Bellis

Castellana Grotte, Italy

National Institute For Digestive Diseases Irccs Saverio Of Bellis

Castellana Grotte, Italy
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Orlando A.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Linsalata M.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | D'Attoma B.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Russo F.,National Institute For Digestive Diseases Irccs Saverio Of Bellis
Journal of Functional Foods | Year: 2017

Celiac disease (CD) is an immune-mediated enteropathy characterized by an increase in paracellular permeability. The improvements in barrier integrity have been related to changes in tight junction (TJ) structure as a consequence of modifications in TJ protein expression. Recently, also polyamines have been suggested to play a part in the control of intestinal permeability by modulating TJ and adherens junction (AJ) expressions. The present work investigated the protective role of Lactobacillus rhamnosus GG (L.GG) towards alterations of the paracellular permeability induced by Pepsin-Trypsin digested Gliadin (PTG) in Caco-2 cells. The results from this study clearly indicate that L.GG protects Caco-2 cells from PTG induced damage and, interestingly, the presence of cellular polyamines seems to be essential in the modulation of TJ and AJ protein expression exerted by this probiotic. On these bases, a role for L.GG as a dietary supplement to promote health also for CD patients could be hypothesized. © 2017 Elsevier Ltd


Russo F.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Linsalata M.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Clemente C.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | D'Attoma B.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | And 4 more authors.
BMC Cancer | Year: 2013

Background: Several GI peptides linked to intestinal barrier function could be involved in the modification of intestinal permeability and the onset of diarrhea during adjuvant chemotherapy. The aim of the study was to evaluate the circulating levels of zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF) and ghrelin and their relationship with intestinal permeability and chemotherapy induced diarrhea (CTD).Methods: Sixty breast cancer patients undergoing an FEC60 regimen were enrolled, 37 patients completed the study. CTD(+) patients were discriminated by appropriate questionnaire and criteria. During chemotherapy, intestinal permeability was assessed by lactulose/mannitol urinary test on day 0 and day 14. Zonulin, GLP-2, EGF and ghrelin circulating levels were evaluated by ELISA tests at five time-points (days 0, 3, 10, 14, and 21).Results: During FEC60 administration, the lactulose/mannitol ratio was significantly higher on day 14 than at baseline. Zonulin levels were not affected by chemotherapy, whereas GLP-2 and EGF levels decreased significantly. GLP-2 levels on day 14 were significantly lower than those on day 0 and day 3, while EGF values were significantly lower on day 10 than at the baseline. In contrast, the total concentrations of ghrelin increased significantly at day 3 compared to days 0 and 21, respectively. Ten patients (27%) suffered from diarrhea. On day 14 of chemotherapy, a significant increase of the La/Ma ratio occurred in CTD(+) patients compared to CTD(-) patients. With regards to circulating gut peptides, the AUCg of GLP-2 and ghrelin were significantly lower and higher in CTD(+) patients than CTD(-) ones, respectively. Finally in CTD(+) patients a significant and inverse correlation between GLP-2 and La/Ma ratio was found on day 14.Conclusions: Breast cancer patients undergoing FEC60 showed alterations in the intestinal permeability, which was associated with modifications in the levels of GLP-2, ghrelin and EGF. In CTD(+) patients, a different GI peptide profile and increased intestinal permeability was found in comparison to CTD(-) patients. This evidence deserves further studies for investigating the potentially different intestinal luminal and microbiota conditions.Trial registration: Clinical trial NCT01382667. © 2013 Russo et al.; licensee BioMed Central Ltd.


Indrio F.,University of Bari | Riezzo G.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Raimondi F.,University of Naples Federico II | Bisceglia M.,Ospedale San Giovanni di Dio | And 3 more authors.
European Journal of Clinical Investigation | Year: 2011

Background: Young infants are frequently affected by uncomplicated regurgitation that may persist despite dietetic and conservative interventions. On this basis, we studied the putative effects of probiotics on the frequency of regurgitation and gastric emptying time in infants with functional gastroesophageal reflux (GER). Patients and methods Forty-two infants with regurgitation were randomized to assume Lactobacillus reuteri DSM 17938 at a dose of 1×10 8CFU per day and placebo for 30days. The episodes of regurgitation were recorded by the parents each day. Gastric emptying time was recorded using real-time ultrasound at baseline and at the end of the study. Twenty-one infants without regurgitation were enroled to compare anthropometric and physiological parameters before the intervention diet. Results Thirty-four infants completed the study (19 infants receiving probiotics and 15 placebo).At baseline, the whole group of infants was similar to the control group as regards anthropometric and physiological data. The median fasting antral area was significantly reduced, (P=0·01) the delta in gastric emptying rate was significantly increased (P=0·01) and the median episodes per day of regurgitation was reduced (, P<0·001) in the probiotic group compared to the placebo group. In the whole group, the frequency of regurgitation and the basal antral area showed a positive correlation (r=0·53, P=0·004). Conclusions: In infants with functional GER, L. reuteri DSM 17938 reduce gastric distension and accelerate gastric emptying. In addition, this probiotic strain seems to diminish the frequency of regurgitation. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.


Russo F.,Laboratory of Experimental Biochemistry | Riezzo G.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Chiloiro M.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | De Michele G.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | And 5 more authors.
Current Pharmaceutical Design | Year: 2010

Different lines of evidence suggest that higher intake of fiber may somehow protect against metabolic syndrome. The prebiotic inulin has widely been studied in relation to its putative beneficial effects on lipid and glucose metabolism. Therefore, adding inulin to diet may be a suitable strategy to prevent metabolic syndrome. Aim of the present study was to evaluate the effects of the daily consumption of inulin-enriched pasta on lipid and glucose metabolism as well as on gastrointestinal motility in young healthy subjects. Methods. Twenty-two healthy young male volunteers entered a randomized double blind cross-over study consisting of a 2-weeks run-in period, two 5-weeks study periods (11% inulin-enriched or control pasta), and an 8-weeks wash-out period in between. Serum lipid and glucose concentrations were evaluated by routine biochemical analyses. Gastric emptying time and electrical activity were non-invasively evaluated by ultrasound and electrogastrography. Data were analyzed by Friedman Repeated Measures ANOVA test. Results. Significant differences among baseline and the treatment group were found for HDL-cholesterol (p=0.004), total cholesterol/HDL-cholesterol ratio (p=0.006), triglycerides (p=0.04), fasting glucose level (p=0.044), fructosamine (p=0.0478), HbA1c (p=0.04), and homeostatic model assessment (HOMA-IR) (p=0.045). The gastric emptying, expressed as final emptying time, was found significantly delayed in the group that assumed inulin-enriched pasta (p=0.008). Conclusions. Inulin-enriched pasta improved lipidic and glicidic metabolism as well as the insulin resistance in healthy young subjects. In addition, it delayed the gastric emptying time which may represent the physiological counterpart of its metabolic effects. © 2010 Bentham Science Publishers Ltd.


Russo F.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Linsalata M.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Clemente C.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Chiloiro M.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | And 4 more authors.
Nutrition Research | Year: 2012

Apart from the intestinal environment, inulin induces physiological effects, which includes a reduction in glucose and lipid concentrations and modulation of gastrointestinal motility through the release of different peptides. We hypothesized that inulin-enriched pasta may also improve small intestine permeability in relation to zonulin and glucagon-like peptide 2 (GLP-2) levels in healthy young subjects. Twenty healthy, young male volunteers completed a randomized, double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods (11% inulin-enriched or control pasta), with an 8-week washout period in between. The intestinal barrier function was assessed by lactulose-mannitol excretion in urine. Zonulin values and GLP-2 release were evaluated by enzyme-linked immunosorbent assay. In the inulin group, the urinary lactulose recovery was significantly lower than the other 2 groups. There were no significant differences in urinary mannitol levels between groups. Accordingly, the lactulose-mannitol excretion ratio was significantly decreased in the inulin-enriched pasta group compared with the other 2 groups. The inulin-enriched pasta group had significantly lower zonulin serum values and significantly higher GLP-2 basal values when compared with the baseline and control pasta groups. The dietary use of inulin-enriched pasta preserves intestinal mucosal barrier functioning and modulates circulating levels of zonulin and GLP-2, suggesting that prebiotics could be used in the prevention of gastrointestinal diseases and metabolic disorders. © 2012 Elsevier Inc.


Indrio F.,University of Bari | Riezzo G.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Cavallo L.,University of Bari | Mauro A.D.,University of Bari | Francavilla R.,University of Bari
Journal of Maternal-Fetal and Neonatal Medicine | Year: 2011

To provide an overview on the role of gut immunity, nervous system and motility patterns in the development of feeding intolerance in newborns. Maturation of the GI is important not only for digestion and absorption, but for endocrine and exocrine function as well. There is little data available about the development of the motility function and of the mucosal barrier of the human gut, and in particular about the motility patterns and mucosal changes in newborns during early days of life. It is known that functional maturation of the gastrointestinal tract is quite different over time with respect to its anatomical development. Besides, the gastrointestinal tract through innate and specific immunologic factors, acts as a defense against ingested antigens. In addition to the mucous membrane integrity and digestion, numerous specific immunologic cells and mediators orchestrate such defensive mechanisms. In case of food antigens, the outcome is usually in favor of tolerance. Defects in that barrier, however, can lead to the development of aberrant immunologic responses, including hypersensitivity reactions. It is obvious that an appropriate feeding regimen during early infancy is in favor of food tolerance. However, in addition to genetic predisposition, development of tolerance is facilitated by an adequate gut barrier (immune or nonimmune), well-coordinated GI motility and nervous network, and appropriate food regimen. © 2011 Informa UK, Ltd.


Orlando A.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Linsalata M.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Notarnicola M.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Tutino V.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Russo F.,National Institute For Digestive Diseases Irccs Saverio Of Bellis
BMC Microbiology | Year: 2014

Background: Celiac disease is characterized by enhanced intestinal paracellular permeability due to alterations of function and expression of tight junction (TJ) proteins including ZO-1, Claudin-1 and Occludin. Polyamines are pivotal in the control of intestinal barrier function and are also involved in the regulation of intercellular junction proteins. Different probiotic strains may inhibit gliadin-induced toxic effects and the Lactobacillus rhamnosus GG (L.GG) is effective in the prevention and treatment of gastrointestinal diseases. Aims of the study were to establish in epithelial Caco-2 cells whether i) gliadin affects paracellular permeability and polyamine profile; ii) co-administration of viable L.GG, heat-killed L.GG (L.GG-HK) or its conditioned medium (L.GG-CM) preserves the intestinal epithelial barrier integrity. Additionally, the effects of L.GG on TJ protein expression were tested in presence or absence of polyamines. Results: Administration of gliadin (1 mg/ml) to Caco-2 cells for 6 h caused a significant alteration of paracellular permeability as demonstrated by the rapid decrease in transepithelial resistance with a concomitant zonulin release. These events were followed by a significant increase in lactulose paracellular transport and a slight lowering in ZO-1 and Occludin expression without affecting Claudin-1. Besides, the single and total polyamine content increased significantly. The co-administration of viable L.GG (108 CFU/ml), L.GG-HK and L.GG-CM with gliadin significantly restored barrier function as demonstrated by transepithelial resistance, lactulose flux and zonulin release. Viable L.GG and L.GG-HK, but not L.GG-CM, led to a significant reduction in the single and total polyamine levels. Additionally, only the co-administration of viable L.GG with gliadin significantly increased ZO-1, Claudin-1 and Occludin gene expression compared to control cells. When Caco-2 cells treated with viable L.GG and gliadin were deprived in the polyamine content by -Difluoromethylornithine, the expression of TJ protein mRNAs was not significantly different from that in controls or cells treated with gliadin alone. Conclusions: Gliadin modifies the intestinal paracellular permeability and significantly increases the polyamine content in Caco-2 cells. Concomitant administration of L.GG is able to counteract these effects. Interestingly, the presence of cellular polyamines is necessary for this probiotic to exert its capability in restoring paracellular permeability by affecting the expression of different TJ proteins. © 2014Orlando et al.; licensee BioMed Central Ltd.


Orlando A.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Linsalata M.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Russo F.,National Institute For Digestive Diseases Irccs Saverio Of Bellis
International Journal of Oncology | Year: 2016

Vitamin K (VK), an essential nutrient associated with the clotting cascade, has also been demonstrated to have anticancer properties in various cancer cells including colon cancer cells. Also probiotics have gained interest as potential anticancer agents. Among them, Lactobacillus rhamnosus GG (L.GG) has been shown to inhibit cell proliferation and polyamine biosynthesis as well as to induce apoptosis in different human gastrointestinal cancer cells. Nevertheless, the exact mechanisms involved in these actions are not completely elucidated. Therefore, the aims of the present study were to evaluate in three differently graded human colon cancer cells (namely Caco-2, HT-29 and SW480) the effects of increasing VK1 concentrations, administered alone or in combination with viable L.GG, on the cell proliferation evaluated by MTT test, apoptosis investigated by Bax/Bcl-2 ratio and the percentage of the apoptotic cells, and the cell cycle evaluated by MUSE cell analyzer. Both VK1 and L.GG administered alone up to 72 h, caused inhibition of proliferation, induction of apoptosis and the cell cycle arrest in all the tested colon cancer cells. When VK1 and L.GG were co-administered, the addition of increasing VK1 concentrations potentiated the probiotic antiproliferative effect in a dose-dependent manner, being also related to the individual features of each cell line. The effect was more evident in Caco-2 and HT-29 cells compared to the less differentiated SW480. The enhanced antiproliferative efficacy due to co-administration of L.GG and VK1 could represent a suitable option in a functional food strategy for cancer growth inhibition and chemoprevention.


Tutino V.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Orlando A.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Russo F.,National Institute For Digestive Diseases Irccs Saverio Of Bellis | Notarnicola M.,National Institute For Digestive Diseases Irccs Saverio Of Bellis
Journal of Cellular Physiology | Year: 2016

The 3T3-L1 preadipocyte cell line is a well characterized cell model for studying the adipocyte status and the molecular mechanisms involved in differentiation of these cells. 3T3-L1 preadipocytes have the ability to synthesize and degrade endocannabinoid anandamide (AEA) and their differentiation into adipocytes increases the expression of cannabinoid (CB1) and PPAR-γ receptors. Clinically, the blocking stimulation of the endocannabinoid pathway has been one of the first approaches proposed to counteract the obesity and obesity-associated diseases (such as diabetes, metabolic syndrome and cancer). In this connection, here we studied in cultured 3T3-L1 pre-adipocytes the effects of n-3-PUFA, α-Linolenic acid (OM-3), n-6-PUFA, Linoleic acid (OM-6), and hydroxytyrosol (HT) on the expression of CB1 receptor gene and the adipogenesis-related genes PPAR-γ, Fatty Acid Synthase (FAS) and Lipoprotein Lipase (LPL). HT was able to inhibit 3T3-L1 cell differentiation by down-regulating cell proliferation and CB1 receptor gene expression. HT exhibited anti-adipogenic effects, whereas OM-3 and OM-6 exerted an inhibitory action on cell proliferation associated with an induction of the preadipocytes differentiation and CB1 receptor gene expression. Moreover, the expression of FAS and LPL genes resulted increased after treatment with both HT and OM-3 and OM-6. The present study points out that the intake of molecules such as HT, contained in extra virgin olive oil, may be considered also in view of antiobesity and antineoplastic properties by acting directly on the adipose tissue and modulating CB1 receptor gene transcription. © 2015 Wiley Periodicals, Inc.


PubMed | National Institute For Digestive Diseases Irccs Saverio Of Bellis
Type: Journal Article | Journal: International journal of oncology | Year: 2016

Vitamin K (VK), an essential nutrient associated with the clotting cascade, has also been demonstrated to have anticancer properties in various cancer cells including colon cancer cells. Also probiotics have gained interest as potential anticancer agents. Among them, Lactobacillus rhamnosus GG (L.GG) has been shown to inhibit cell proliferation and polyamine biosynthesis as well as to induce apoptosis in different human gastrointestinal cancer cells. Nevertheless, the exact mechanisms involved in these actions are not completely elucidated. Therefore, the aims of the present study were to evaluate in three differently graded human colon cancer cells (namely Caco-2, HT-29 and SW480) the effects of increasing VK1 concentrations, administered alone or in combination with viable L.GG, on the cell proliferation evaluated by MTT test, apoptosis investigated by Bax/Bcl-2 ratio and the percentage of the apoptotic cells, and the cell cycle evaluated by MUSE cell analyzer. Both VK1 and L.GG administered alone up to 72h, caused inhibition of proliferation, induction of apoptosis and the cell cycle arrest in all the tested colon cancer cells. When VK1 and L.GG were co-administered, the addition of increasing VK1 concentrations potentiated the probiotic antiproliferative effect in a dose-dependent manner, being also related to the individual features of each cell line. The effect was more evident in Caco-2 and HT-29 cells compared to the less differentiated SW480. The enhanced antiproliferative efficacy due to co-administration of L.GG and VK1 could represent a suitable option in a functional food strategy for cancer growth inhibition and chemoprevention.

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