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.

Alterations of the small-intestinal permeability (s-IP) might play an essential role in both diarrhoea-predominant IBS (D-IBS) and celiac disease (CD) patients. Our aims were to analyse in D-IBS patients the symptom profile along with the levels of urinary sucrose (Su), lactulose (La), mannitol (Ma), and circulating biomarkers (zonulin, intestinal fatty acid binding protein - I-FABP, and diamine oxidase - DAO) of the gastrointestinal (GI) barrier function. The pro-inflammatory interleukins 6 and 8 (IL-6 and IL-8), the plasma values of lipopolysaccharide (LPS), and Toll-like receptor 4 (TLR-4) were also investigated. Besides, these biomarkers were compared with those in CD and healthy controls (HC). Finally, comparisons were performed between D-IBS patients with [D-IBS(+)] and without [D-IBS(−)] increased s-IP according to normal or altered La/Ma ratio. The study included 39 D-IBS patients, 32 CD patients, and 20 HC. GI permeability was assayed by high-performance liquid chromatography determination in the urine of Su and La/Ma ratio. ELISA kits assayed circulating concentrations of zonulin, I-FABP, DAO, IL-6, IL-8, LPS, and TLR-4. The Mann–Whitney or the Kruskal–Wallis with Dunn’s post-test was used to assess differences among the groups. As for the La/Ma ratio, %Su, and I-FABP levels, D-IBS patients were significantly different from CD, but not HC. IL-6 levels were significantly higher in CD than HC, whereas IL-8 levels were significantly higher in both D-IBS and CD patients than HC. By opposite, LPS, and TLR-4 concentrations did not differ significantly among the groups. When D-IBS patients were categorised according to normal or altered s-IP, D-IBS(+) patients had %La, %Su, I-FABP, and DAO levels significantly higher than D-IBS(−) ones. The inflammatory parameters and markers of bacterial translocation (namely, IL-6 and LPS) were significantly higher in D-IBS(+) patients than D-IBS(−) ones. The present study suggests that two distinct D-IBS subtypes could be identified. The investigation of possible s-IP alterations (i.e., considering the La/Ma ratio) might be useful to assess better and categorise this heterogeneous D-IBS population. NCT01574209 . Registered March 2012. First recruitment started in April 2012.

Celiac disease (CD) is a chronic immune-mediated disorder, characterized by enhanced paracellular permeability across the intestinal epithelium. The complex system of intercellular junctions, including tight junctions (TJs) and adherens junctions (AJs), seals together the epithelial cells to form a continuous layer. The improvements in barrier integrity have been related to modifications in intercellular junction protein expression. Polyamines (spermidine, spermine, and putrescine) actively participate in the modulation of the AJ expression. Both in vitro and in vivo studies have demonstrated that also probiotics can promote the integrity and the function of the intestinal barrier. On these bases, the present work investigated the protective effects exerted by Lactobacillus rhamnosus GG (L.GG) against the pepsin-trypsin-digested gliadin (PTG)-induced enteropathy in jejunal tissue samples of Wistar rats. In particular, the probiotic effects have been evaluated on the intestinal mucosal architecture, polyamine metabolism and intercellular junction protein expression (ZO-1, Occludin, Claudin-1, β-catenin and E-cadherin). The results from this study indicate that L.GG protects the intestinal mucosa of rats from PTG-induced damage, by preventing the reduction of the expression of the intercellular junction proteins. Consequently, a role for L.GG in the therapeutic management of the gluten-related disorders in humans could be hypothesized.

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (LFD) improves both gastrointestinal (GI) symptoms and the psychological profile of patients with irritable bowel syndrome with diarrhea (IBS-D). The effects of 12 weeks of LFD on GI symptom and psychological profiles in relation to inflammation and the involvement of the intestinal barrier were studied in twenty IBS-D patients. The IBS Severity Scoring System, the Symptom Checklist-90-Revised, the Italian version of the 36-Item Short-Form Health Survey, the IBS-Quality of Life (QoL) questionnaire, and the Psychophysiological questionnaire were administered. The GI barrier function was assessed by sugar absorption test, the serum and fecal zonulin levels, and the serum levels of intestinal fatty-acid binding protein and diamine oxidase. Interleukins (ILs) and lipopolysaccharide (LPS) serum levels were evaluated along with dysbiosis. At the end of LFD, GI symptoms, psychological state (mainly anxiety, somatization, psychoticism, and interpersonal sensitivity), and QoL significantly improved in these patients. Simultaneously, an improvement in small intestinal permeability and intestinal mucosal integrity occurred, while IL-6, Il-10, LPS, and fermentative dysbiosis significantly decreased. The LFD can modify the immune-inflammatory features and enhance intestinal permeability and mucosal integrity, thus determining a concurrent improvement in the clinical and psychological conditions.

The very-low-calorie ketogenic diet (VLCKD) is effective and safe for obese individuals, but limited information exists on its impact on the intestinal barrier. This study analyzed the effects of 8 weeks of VLCKD on 24 obese patients (11M/13F). Carbohydrate intake was fixed at 20–50 g/day, while protein and lipid intake varied from 1–1.4 g/kg of ideal body weight and 15–30 g per day, respectively. Daily calorie intake was below 800 kcal. The lactulose–mannitol absorption test assessed small intestinal permeability. Multiple markers, such as serum and fecal zonulin, fatty acid-binding protein, diamine oxidase concentrations, urinary dysbiosis markers (indican and skatole), and circulating lipopolysaccharide levels, were analyzed. Inflammation markers (serum interleukin 6, 8, 10, and tumor necrosis factor-α concentrations) were also evaluated. The results showed significant reductions in weight, BMI, and waist circumference post-diet. However, the lactulose–mannitol ratio increased by 76.5%, and a significant increase in dysbiosis markers at the end of the diet occurred. This trend was particularly evident in a subgroup of patients. Despite initial benefits, the VLCKD might negatively affect the intestinal barrier function in obese patients, potentially worsening their compromised intestinal balance.

Decreased serum vitamin D (VD) levels have been associated with gastrointestinal (GI) disorders, including irritable bowel syndrome (IBS). VD can also modulate the intestinal barrier. Given the link between the GI barrier’s alterations and diet, attention has aroused the positive effects of the Low FODMAP Diet (LFD) on IBS patients’ symptom profile. We evaluated the GI symptoms and the urinary and circulating markers of GI barrier function, the markers of inflammation and intestinal dysbiosis in 36 IBS patients with predominant diarrhea (IBS-D) (5 men and 31 women, 43.1 ± 1.7 years) categorized for their circulating VD levels in low (L-VD) and normal (N-VD) (cutoff = 20 ng/mL). Evaluations were performed before and after 12 weeks of LFD. At the baseline, L-VD patients showed a significantly worse symptom profile and altered small intestinal permeability (s-IP) than N-VD. After LFD, a significant increase in the circulating VD levels in both the subgroups and a significant improvement of s-IP in L-VD patients occurred. Finally, VD levels negatively correlated with the symptom score and fecal zonulin. These data highlight the close relationship between VD and the intestinal barrier and support their involvement in IBS-D pathophysiology. Moreover, the potentially positive role of LFD in the management of IBS-D was confirmed.