Effect of a 12-Week Walking Program Monitored by Global Physical Capacity Score (GPCS) on Circulating Cell-Free mtDNA and DNase Activity in Patients with Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) involves low-grade mucosal inflammation. Among the various approaches capable of managing the symptoms, physical activity is still under investigation. Despite its benefits, it promotes oxidative stress and inflammation. Mitochondria impacts gut disorders by releasing damage-associated molecular patterns, such as cell-free mtDNA (cf-mtDNA), which support inflammation. This study evaluated the effects of a 12-week walking program on the cf-mtDNA and DNase in 26 IBS and 17 non-IBS subjects. Pro- and anti-inflammatory cytokines were evaluated by ELISA. Digital droplet PCR was used to quantify cf-mtDNA; DNase activity was assessed using a single radial enzyme diffusion assay. PCR-RFLP was used to genotype DNASE1 rs1053874 SNP. Significantly lower IL-10 levels were found in IBS than in non-IBS individuals. Exercise reduced cf-mtDNA in non-IBS subjects but not in IBS patients. DNase activity did not correlate with the cf-mtDNA levels in IBS patients post-exercise, indicating imbalanced cf-mtDNA clearance. Different rs1053874 SNP frequencies were not found between groups. The study confirms the positive effects of regular moderate-intensity physical activity in healthy subjects and its role in cf-mtDNA release and clearance. Walking alone might not sufficiently reduce subclinical inflammation in IBS, based on imbalanced pro- and anti-inflammatory molecules. Prolonged programs are necessary to investigate their effects on inflammatory markers in IBS.

Somatization in patients with predominant diarrhoea irritable bowel syndrome: the role of the intestinal barrier function and integrity.

BACKGROUND: Irritable bowel syndrome (IBS) is characterised by gastrointestinal (GI) and psychological symptoms (e.g., depression, anxiety, and somatization). Depression and anxiety, but not somatization, have already been associated with altered intestinal barrier function, increased LPS, and dysbiosis. The study aimed to investigate the possible link between somatization and intestinal barrier in IBS with diarrhoea (IBS-D) patients. METHODS: Forty-seven IBS-D patients were classified as having low somatization (LS = 19) or high somatization (HS = 28) according to the Symptom Checklist-90-Revised (SCL-90-R), (cut-off score = 63). The IBS Severity Scoring System (IBS-SSS) and the Gastrointestinal Symptom Rating Scale (GSRS) questionnaires were administered to evaluate GI symptoms. The intestinal barrier function was studied by the lactulose/mannitol absorption test, faecal and serum zonulin, serum intestinal fatty-acid binding protein, and diamine oxidase. Inflammation was assessed by assaying serum Interleukins (IL-6, IL-8, IL-10), and tumour necrosis factor-α. Dysbiosis was assessed by the urinary concentrations of indole and skatole and serum lipopolysaccharide (LPS). All data were analysed using a non-parametric test. RESULTS: The GI symptoms profiles were significantly more severe, both as a single symptom and as clusters of IBS-SSS and GSRS, in HS than LS patients. This finding was associated with impaired small intestinal permeability and increased faecal zonulin levels. Besides, HS patients showed significantly higher IL-8 and lowered IL-10 concentrations than LS patients. Lastly, circulating LPS levels and the urinary concentrations of indole were higher in HS than LS ones, suggesting a more pronounced imbalance of the small intestine in the former patients. CONCLUSIONS: IBS is a multifactorial disorder needing complete clinical, psychological, and biochemical evaluations. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03423069 .

Noninvasive biomarkers of gut barrier function identify two subtypes of patients suffering from diarrhoea predominant-IBS: a case-control study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: NCT01574209 . Registered March 2012. First recruitment started in April 2012.

Lactobacillus GG restoration of the gliadin induced epithelial barrier disruption: the role of cellular polyamines.

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 (10(8) 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 α-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.

A Multi-Omics Approach to Disclose Metabolic Pathways Impacting Intestinal Permeability in Obese Patients Undergoing Very Low Calorie Ketogenic Diet.

A very low calorie ketogenic diet (VLCKD) impacts host metabolism in people marked by an excess of visceral adiposity, and it affects the microbiota composition in terms of taxa presence and relative abundances. As a matter of fact, there is little available literature dealing with microbiota differences in obese patients marked by altered intestinal permeability. With the aim of inspecting consortium members and their related metabolic pathways, we inspected the microbial community profile, together with the set of volatile organic compounds (VOCs) from untargeted fecal and urine metabolomics, in a cohort made of obese patients, stratified based on both normal and altered intestinal permeability, before and after VLCKD administration. Based on the taxa relative abundances, we predicted microbiota-derived metabolic pathways whose variations were explained in light of our cohort symptom picture. A totally different number of statistically significant pathways marked samples with altered permeability, reflecting an important shift in microbiota taxa. A combined analysis of taxa, metabolic pathways, and metabolomic compounds delineates a set of markers that is useful in describing obesity dysfunctions and comorbidities.

The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study.

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.

Adipokine profile in celiac patients: differences in comparison with patients suffering from diarrhea-predominant IBS and healthy subjects.

OBJECTIVE. The role of adipokines such as resistin, leptin, and adiponectin could be pivotal in the molecular crosstalk between the inflamed intestine and the surrounding mesenteric adipose tissue. Our aims were to a) evaluate their circulating concentrations in patients with active celiac disease (ACD) and compare them to those in patients with diarrhea-predominant irritable bowel syndrome (IBS-d) and healthy subjects; b) establish the impact of genetic variability in resistin; and c) evaluate whether a 1-year gluten-free diet (GFD) modifies circulating concentrations of resistin, leptin, and adiponectin in celiac patients. MATERIAL AND METHODS. The study included 34 ACD patients, 29 IBS-d patients, and 27 healthy controls. Circulating concentrations of resistin, leptin, adiponectin, IL-6, and IL-8 were evaluated at the time of enrollment. Resistin +299 G/A polymorphism was also analysed. In CD patients, biochemical measurements were repeated after a 1-year GFD. RESULTS. Along with higher IL-6 and IL-8 plasma levels, higher resistin and adiponectin concentrations were found in ACD and IBS-d patients compared with controls (p: 0.0351 and p: 0.0020, respectively). Resistin values proved to be predictable from a linear combination of IL-8 and +299 polymorphism. GFD affected resistin (p: 0.0009), but not leptin and adiponectin concentrations. CONCLUSIONS. Our data suggest that these adipokines are involved in modulating inflammatory processes in both CD and IBS-d patients. Alterations in the adipokine profile as well as the higher prevalence of the resistin +299 G/A SNP A allele compared to controls support the hypothesis that, at least in well-defined cases of IBS, a genetic component may also be supposed.

Somatization is associated with altered serum levels of vitamin D, serotonin, and brain-derived neurotrophic factor in patients with predominant diarrhea irritable bowel syndrome.

BACKGROUND: Patients with irritable bowel syndrome (IBS) often show psychological disorders, including somatization, usually driven by an altered gut-brain axis. These changes are also accompanied by modifications in the circulating levels of vitamin D (VD) and neurotransmitters such as serotonin (5-HT) and brain-derived neurotrophic factor (BDNF). The present study aimed to evaluate the relationship between gastrointestinal (GI) symptoms and circulating levels of VD, 5-HT, and BDNF in IBS patients with diarrhea (IBS-D) categorized according to somatization. METHODS: Fifty-three IBS-D patients were recruited and profiled for GI symptoms by validated questionnaires. The fasting serum concentrations of VD, 5-HT, and BDNF were assessed. The health of the intestinal barrier, minimal inflammation, and dysbiosis was also evaluated. KEY RESULTS: Thirty patients showed high somatization scores, IBS-D(S+), and 23 low somatization scores, IBS-D(S-). IBS-D(S+) patients reported higher "Abdominal pain" and the "Abdominal pain duration in days" scores, lower serum VD levels and increased 5-HT and BDNF concentrations than IBS-D(S-). Besides, in IBS-D(S+) patients, the GI symptoms correlated with 5HT, BDNF, and VD concentrations. These parameters were associated with impaired small intestinal permeability and increased inflammation markers. CONCLUSIONS AND INFERENCES: These data support the multifactorial IBS pathogenesis in which organic and psychological factors interact. An active role by VD, 5-HT, and BDNF in affecting the clinical and biochemical profiles in IBS-D(S+) patients may be conceivable. Therefore, the routine VD estimation and the assay of circulating levels of 5-HT and BDNF could be considered a new approach for managing these patients.

Corrigendum: Managing symptom profile of IBS-D patients with Tritordeum-based foods: results from a pilot study.

[This corrects the article DOI: 10.3389/fnut.2022.797192.].

A Tritordeum-Based Diet for Female Patients with Diarrhea-Predominant Irritable Bowel Syndrome: Effects on Abdominal Bloating and Psychological Symptoms.

Most female patients with irritable bowel syndrome (IBS) complain of abdominal bloating rather than abdominal pain and diarrhea. The higher incidence in women could be due to the so-called dysfunctional gas handling. Since diet seems the most effective and durable strategy for managing IBS symptoms, we aimed to evaluate the effects of a 12 week diet based on a relatively new cereal, Tritordeum (TBD), on gastrointestinal (GI) symptoms, anthropometric and bioelectrical impedance parameters, and psychological profiles in 18 diarrhea-predominant IBS (IBS-D) female patients with abdominal bloating as the dominant symptom. The IBS Severity Scoring System (IBS-SSS), the Symptom Checklist-90 Revised, the Italian version of the 36-Item Short-Form Health Survey, and the IBS-Quality of Life questionnaire were administered. The TBD reduces the IBS-SSS "Intensity of abdominal bloating" with a concomitant improvement in the anthropometric profile. No correlation was found between "Intensity of abdominal bloating" and "Abdominal circumference". Anxiety, depression, somatization, interpersonal sensitivity, and phobic and avoidance manifestations were significantly reduced after TBD. Lastly, anxiety was correlated with "Intensity of abdominal bloating". Overall, these results suggest the possibility of lowering abdominal bloating and improving the psychological profile of female IBS-D patients using a diet based on an alternative grain such as Tritordeum.

The Role of Intestinal Barrier Function in Overweight Patients with IBS with Diarrhea Undergoing a Long-Term Low Fermentable Oligo-, Di-, and Monosaccharide and Polyol Diet.

Overweight and obesity have been suggested as significant factors in irritable bowel syndrome (IBS) development. However, the relationship between overweight/obesity and IBS is unclear. It is known that a modified intestinal barrier, especially the permeability of the small intestine (s-IP), can play a significant role in the pathogenesis of both obesity and IBS. Moreover, dietary interventions are essential for treating both pathologies. We evaluated the gastrointestinal (GI) symptoms and the urinary and circulating markers of GI barrier function and integrity, the markers of intestinal dysbiosis and bacterial translocation, in 40 IBS patients with predominant diarrhea (IBS-D) (32 females and 8 males; mean age = 43.5 ± 1.4 years), categorized using their Body Mass Index levels as normal (NW) and overweight (OW). Evaluations were performed before and after 12 weeks of a Low FODMAP Diet (LFD). At the baseline, OW patients showed a significantly higher s-IP than NW. After an LFD, a significant improvement of s-IP in OW patients occurred, along with a significant decrease in markers of epithelial integrity and bacterial translocation. Our findings highlight the close relationship between overweight and the intestinal barrier and support their involvement in IBS-D pathophysiology. Furthermore, the positive role of an LFD in managing overweight IBS-D was highlighted.

The Effects of a Very-Low-Calorie Ketogenic Diet on the Intestinal Barrier Integrity and Function in Patients with Obesity: A Pilot Study.

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.

Effects of a Very-Low-Calorie Ketogenic Diet on the Fecal and Urinary Volatilome in an Obese Patient Cohort: A Preliminary Investigation.

Several recent studies deepened the strong connection between gut microbiota and obesity. The effectiveness of the very-low-calorie ketogenic diet (VLCKD) has been measured in terms of positive impact on the host homeostasis, but little is known of the modification exerted on the intestinal metabolome. To inspect this complex relationship, we analyzed both fecal and urinary metabolome in terms of volatile organic compounds (VOCs) by the GC-MS method in 25 obese patients that were under VLCKD for eight weeks. Partial least square discriminant analysis evidenced specific urinary and fecal metabolites whose profile can be considered a signature of a partial restore toward the host eubiosis. Specifically, among various keystone VOCs, the decreased concentration of four statistically significant fecal esters (i.e., propanoic acid pentyl ester, butanoic acid hexyl ester, butanoic acid pentyl ester, and pentanoic acid butyl ester) supports the positive effect of VLCKD treatment. Our pilot study results suggest a potential positive effect of VLCKD intervention affecting fecal and urinary volatilome profiles from obese patients. Meta-omics techniques including the study of genes and transcripts will help in developing new interventions useful in preventing or treating obesity and its associated health problems.

Metabolomic Profiling of Obese Patients with Altered Intestinal Permeability Undergoing a Very Low-Calorie Ketogenic Diet.

A healthy intestinal permeability facilitates the selective transport of nutrients, metabolites, water, and bacterial products, involving cellular, neural, hormonal, and immune factors. An altered intestinal permeability indicates pathologic phenotypes and is associated with the exacerbation of obesity and related comorbidities. To investigate the impact of altered permeability in obese patients undergoing a calorie-restrictive dietary regimen (VLCKD), we collected urinary and fecal samples from obese patients with both normal and altered permeability (determined based on the lactulose/mannitol ratio) before and after treatment. The analysis of volatile organic compounds (VOCs) aids in understanding the metabolites produced by the intestinal microbiota in this unique ecological niche. Furthermore, we examined clinical and anthropometric variables from the cohort and compared them to significant VOC panels. Consequently, we identified specific markers in the metabolomics data that differentiated between normal and altered profiles before and after the diet. These markers indicated how the variable contribution specifically accounted for interleukins and lipopolysaccharides (LPS). The targeted metabolomics experiment detected no differences in measured short-chain fatty acids (SCFA). In summary, our study evaluated metabolomic markers capable of distinguishing low-grade inflammation conditions, exacerbated in more advanced stages of obesity with altered intestinal permeability.

A Comparison of the Low-FODMAPs Diet and a Tritordeum-Based Diet on the Gastrointestinal Symptom Profile of Patients Suffering from Irritable Bowel Syndrome-Diarrhea Variant (IBS-D): A Randomized Controlled Trial.

The dietary approach low in oligosaccharides, disaccharides, monosaccharides, and fermentable polyols (FODMAPs-LFD) is a good strategy for treating irritable bowel syndrome (IBS). Beyond the LFD, other dietary approaches with beneficial effects may be hypothesized. Among them, consumption of Tritordeum-based foods (TBD, bread, bakery products, and pasta) in substitution of other cereals seem to achieve promising results. In a randomized controlled trial, we compared the effects of 12 weeks of LFD to TBD in improving the symptom profile of IBS-diarrhea (IBS-D) patients. The two diets equally improved gastrointestinal symptoms and QoL, measured by the IBS Severity Scoring System (IBS-SSS) questionnaire, reducing the total score after four weeks and maintaining this range until the end of treatment (IBS-SSS total score change: −132.1; 95% CI: −74.9 to −189.4 and −130.5; 95% CI: −73.2 to −187.7; p < 0.0001 after LFD and TBD, respectively). The two diets did not modify the micronutrients content when extended for 12 weeks. LFD could be regarded as a first-line dietary approach for IBS-D patients. However, TBD may represent a valid alternative, with high palatability, especially among Italian patients, for whom pasta is considered one of the main assets of dietetic culture, and would be easier to manage in their daily habits.

Managing Symptom Profile of IBS-D Patients With Tritordeum-Based Foods: Results From a Pilot Study.

In the past few years, increasing attention has been given to the pathologic role of specific foods in IBS, like wheat and other cereals. Recent literature describes IBS patients who may experience gastrointestinal (GI) and extra-GI symptoms precipitated by the ingestion of cereals. Tritordeum is a cereal of Spanish origin derived from the hybridization of durum wheat and wild barley. It is different from classic wheat for its gluten protein composition, with fewer carbohydrates and fructans and a higher content of proteins, dietary fibers, and antioxidants. This pilot study aimed to investigate the effects of a 12-week diet with Tritordeum-based foods in substitution of other cereals on the profile of GI symptoms (evaluated by appropriate questionnaire) and the health of the GI barrier (assessed by sugar absorption test and different markers of integrity and functions) in 16 diarrhea-predominant IBS (IBS-D) patients. The diet with Tritordeum-based foods (bread, bakery products, and pasta) significantly reduced IBS-D patients' symptoms. This amelioration appears to occur through an overall improvement of the GI barrier, as demonstrated by the reduced intestinal permeability and the decreased levels of markers of intestinal mucosal integrity, mucosal inflammation, and fermentative dysbiosis.

Effects of a diet with inulin-enriched pasta on gut peptides and gastric emptying rates in healthy young volunteers.

AIM: Our group has previously shown that the administration of pasta enriched along with the prebiotic inulin induces a significant reduction in triglyceride and glucose levels with a significant delay in gastric emptying (GE) rates. This protective effect may occur by affecting the release of a number of gut peptides involved in the control of gastrointestinal motility. The aim of the present study was to evaluate the effects of inulin-enriched pasta on the circulating levels of neurotensin (NT), somatostatin (SS), and corticotropin-releasing factor (CRF) in relation to the GE time in young healthy subjects. METHODS: 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/control pasta), with an 8-week wash-out period in between. Gut peptide concentrations were evaluated by radioimmunoassay. GE time was evaluated by ultrasonography. RESULTS: The prebiotic treatment significantly increased the area under the curve (AUC) values of both NT and SS (p < 0.05 Dunn's post-test). With regard to gastric motility, along with a significant delay in both the final time and T (1/2) gastric emptying time, a positive correlation was found between T (1/2) and SS AUC values (r = 0.57, p = 0.009) in the inulin-enriched pasta group. CONCLUSION: These results support the hypothesis that inulin plays an active role in mechanisms affecting the release of these gut peptides, which may modulate the gastric emptying of digesta.

Psychological and Gastrointestinal Symptoms of Patients with Irritable Bowel Syndrome Undergoing a Low-FODMAP Diet: The Role of the Intestinal Barrier.

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 Relationship between Low Serum Vitamin D Levels and Altered Intestinal Barrier Function in Patients with IBS Diarrhoea Undergoing a Long-Term Low-FODMAP Diet: Novel Observations from a Clinical Trial.

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.

Noninvasive Biomarkers of Gut Barrier Function in Patients Suffering from Diarrhea Predominant-IBS: An Update.

The intestinal barrier plays a crucial role in the absorption of nutrients and in preventing the entry of pathogenic microorganisms and toxic molecules. Several studies have shown a compromised intestinal barrier associated with low-grade inflammation in the small intestinal mucosa in celiac disease, inflammatory bowel disease, and irritable bowel syndrome (IBS), particularly in IBS with diarrhea (IBS-D). In light of these new data, IBS is no longer considered a functional disease but rather a heterogeneous syndrome that has yet to be carefully studied. Therefore, investigating the integrity and function of the intestinal barrier is now essential to improving knowledge of the pathophysiology of IBS-D and to improving the management of IBS-D patients. However, the study of the intestinal barrier must clarify some still unsolved methodological aspects and propose standardised assays before becoming a useful diagnostic tool. In this framework, this review will discuss data about the tests that noninvasively evaluate the integrity and functionality of the human intestinal barrier, paying particular attention to patients with IBS-D, in both clinical and research situations.