Olive Tree Biophenols in Inflammatory Bowel Disease: When Bitter is Better.

The current therapeutic scenario for inflammatory bowel diseases (IBD) involves aminosalicylates, corticosteroids, and immunomodulators, but concerns regarding their safety profiles and high costs heavily impact their widespread use. In recent years, the beneficial effects thatbiophenols-from fruit and vegetables-have on human health have been investigated. The antioxidant and anti-inflammatory properties of phenolic fraction, from olive leaves and fruits, have been suggested, and a potential application in gut inflammation has been supported by in vitro and IBD-animal models studies. In the present review, we first introduced the potential therapeutic role of olive tree biophenolsin chronic inflammatory disease. Then, we aimed to describe their most interesting application for gut inflammation, as the results of basic science studies and animal experimental models. Finally, the potential role of olive tree biophenols in the setting of human IBD is discussed.

Use of Complementary and Alternative Medicine by Patients with Irritable Bowel Syndrome According to the Roma IV Criteria: A Single-Center Italian Survey.

Aim: This study was conducted to evaluate the impact of complementary and alternative medicine (CAM) in patients with irritable bowel syndrome (IBS) as assessed by the Rome IV criteria. Methods: Consecutive patients referring for IBS were re-evaluated according to the Rome IV criteria. Demographic features and characteristics potentially associated with the use of CAM were collected. A validated, self-administered, survey questionnaire dealing with CAM and patients' level of knowledge, motivation, perception, and information seeking-behavior toward the use of CAM was analyzed. Multivariate logistic regression analysis was performed in order to identify predictors of CAM use among participants. Results: Among 156 patients claiming IBS, 137 (88%) met the Rome IV criteria, and 62 of them (45%) were CAM users. Biologically based therapy was the most chosen CAM (78%). Significant risk factors (adjusted odds ratio, 95% confidence interval) for the use of CAM were female gender (7.22, 2.31⁻22.51), a higher BMI (1.16, 1.02⁻1.33), and a good knowledge of CAM (4.46, 1.73⁻11.45), while having children was a protective factor (0.25, 0.07⁻0.95). Only 19% of patients used CAM due to medical advice and over half (51%) thought it was a "more natural" approach. Although a minority of patients (16%) had full satisfaction from CAM, 81% of users would repeat the CAM experience for their IBS symptoms. Conclusions: The widespread use of CAM in IBS, the patients' belief in its safety, and their willingness to re-use it suggest that knowledge of health-care providers and patient education should be improved.

Self-Prescribed Dietary Restrictions are Common in Inflammatory Bowel Disease Patients and Are Associated with Low Bone Mineralization.

Background and objectives: Despite the serious concerns of patients about the role of food in triggering or ameliorating their intestinal disease, there are few studies dealing with patients' beliefs and practices regarding diet in inflammatory bowel disease (IBD). The aim of this study was to investigate how the disease affected the dietary habits of patients with IBD, and to assess if patients' food restrictions were responsible for low bone mineralization. Materials and Methods: For this study, 90 consecutive patients referred for IBD were interviewed regarding their dietary habits. Demographic features and clinical characteristics potentially associated with the dietary habits were collected. A validated and self-administered survey questionnaire dealing with dietary habits and patients' beliefs and perceptions regarding food was analyzed. Multivariate logistic regression analysis was performed in order to identify risk factors for dietary restrictions among participants and to evaluate the relationship between dietary restrictions and low bone mineral density (BMD). Results: Among the 63 (70%) patients who claimed a self-prescribed dietary restriction, 84% avoided dairy products. Significant risk factors (adjusted odds ratio (OR), 95% confidence interval (CI)) for the dietary restrictions were a younger age (p = 0.02), a higher level of education (p = 0.007), and a higher visceral sensitivity index (p = 0.009). Most (80%) of the patients displayed an inadequate calcium intake, and an abnormal result at dual-energy X-ray absorptiometry (DXA) scan accounting for low BMD was reported in 46 (51%) of them. Dietary restrictions (p = 0.03), and in particular avoiding dairy products(p = 0.001), were significant risk factors for a low BMD, along with female gender (p = 0.001), smoking(p = 0.04), and steroid abuse (p = 0.03). Almost all (86%) patients changed their diet after IBD diagnosis, as 8% believed that foods could have been a trigger for IBD and 37% that a proper diet was more important than drugs in controlling disease. Although 61% of the patients claimed to have received nutritional advice, 78% of the participants showed interest in receiving more. Conclusions: Dietary habits of IBD patients should be investigated by healthcare professionals as part of the routine visit. Clinicians are invited to provide nutritional recommendations to these patients in order to avoid unnecessary self-prescribed dietary restrictions.

Enhanced expression of indoleamine 2,3-dioxygenase in Helicobacter pylori-infected human gastric mucosa modulates Th1/Th2 pathway and interleukin 17 production.

BACKGROUND: Indoleamine 2,3 dioxygenase (IDO) interferes with immune responses. Host immune response against Helicobacter pylori is involved in the persistence of the infection and its related diseases. AIM: To investigate the role of IDO in the regulation of Th1/Th2 and Th17 pathways in H. pylori infection. METHODS: Gastric biopsy samples were taken from 42 patients who underwent endoscopy and evaluated for the expression of IDO by Western blotting. Gastritis was assessed by the Sydney system score. In a subgroup of patients, biopsies were treated with the IDO inhibitor 1-methyl-L-tryptophan and the expression of interferon-γ (IFN-γ) mRNA and that of T-bet, interleukin-17 (IL-17), and IL-4 determined by real-time PCR and Western blotting, respectively. RESULTS: IDO expression was found to be enhanced (p = .001) in gastric biopsies from H. pylori-infected (n = 18) compared with uninfected (n = 24) patients. Levels of IDO expression were inversely related to the gastritis score (r = -.684, p = .002) in H. pylori-infected gastric mucosa, but not in uninfected mucosa. In gastric biopsy cultures, IDO inhibition increased the expression of IFN-γ mRNA (p = .014), T-bet (p = .045), and IL-17 (p = .02) while decreasing that of IL-4 (p = .048). CONCLUSIONS: In H. pylori-infected human gastric mucosa, an enhanced expression of IDO is capable of modulating Th1/Th2 and Th17 pathways. This mechanism lowers gastric inflammation, possibly contributing to the persistence of H. pylori. Targeting the IDO pathway may be a new strategy for modulating H. pylori-induced mucosal immune response.

High exposure, spontaneous clearance, and low incidence of active Helicobacter pylori infection: the Sorbo San Basile study.

BACKGROUND: A decreased incidence of Helicobacter pylori infection has been prospected to occur nowadays. AIM: To evaluate the exposure to H. pylori, prevalence and incidence of active infection, and related risk factors in the general population. METHODS: In a small town of Southern Italy (932 inhabitants), 595 (3-97 years) and 157 (12-82 years) subjects among those with no evidence of active H. pylori infection participated at baseline and 10 years later, respectively. A questionnaire was administered. Active H. pylori infection was assessed by (13) C-urea breath test (UBT). Serum VacA and CagA antibodies were determined. RESULTS: Of 518 subjects who were evaluated by both UBT and serology, 310 (59.8%) were UBT positive, 479 (92.4%) VacA positive, and 369 (71.2%) CagA positive. Subjects UBT negative and serology positive were 169 (32%), ranging 1 (14.2%) to 29 (82.8%) from last to first decades of life. Age, female gender, and people per room were independent risk factors for subjects UBT positive compared to those UBT negative and serology positive. Ten years later, subjects who became UBT positive were four of 157 (0.25% per year) while those who became seropositive for VacA and/or CagA were 17 of 26 (6.5% per year). CONCLUSIONS: H. pylori infection is highly dynamic with wide range of spontaneous clearance. It is easily cleared in the first decades of life, more recent years, less crowded homes, and males. It disappears and recurs more often than it was previously thought, implying that the current decline in its prevalence is due to real clearance instead of a fall in infection rate.

Real-life burden of adverse reactions to biological therapy in inflammatory bowel disease: a single-centre prospective case series.

BACKGROUND/AIM: Biologics represent a key therapeutic option in inflammatory bowel disease (IBD), but are associated with several side effects. Post-marketing surveillance, through a spontaneous adverse drug reactions (ADRs) monitoring system, is essential to assess the safety profile of biologics. The aim of the study was to prospectively evaluate the occurrence of ADRs in IBD patients treated with biologics from a single centre in Southern Italy. METHODS: Data from patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) who underwent biological therapy were prospectively collected. ADRs were classified according to the Medical Dictionary for Regulatory Activities (MedDRA®). RESULTS: Overall, 68 (54% male, 68% with UC and 32% with CD) biologic-naïve IBD patients underwent biological therapy. Mean follow-up was 11.7 ± 6.2 months. As a results of switches, for 68 patients we obtained 96 biologic prescriptions. Overall, 45 ADRs occurred in 36 (53%) patients, distributed as follows (ADRs/prescriptions): 19/37 with IFX-Remicade, 5/12 with IFX-Remsima, 8/9 with GOL, 11/26 with ADA, and 2/12 with VDZ. Mild ADRs were 29 (64%), moderate 15 (34%) and 1 (2%) severe. General disorders and administration related reactions were the most frequent ADRs (35%), followed by skin and subcutaneous tissue disorders (20%), infections (15%), musculoskeletal (11%), respiratory (6%) blood (4%), gastrointestinal (4%), and vascular disorders (2%). In 9 cases (20%) the ADRs resulted in definitive discontinuation of biologic therapy. CONCLUSION: In a prospective cohort of IBD patients, more than half experienced ADRs during biologic therapy. General disorders and administration related reactions were the most common ADRs, while infections were less common and rarely led to discontinuation of therapy. Findings underline the importance of surveillance in management of IBD patients during biologic therapy and implementing safety protocols with data from real-life settings.

Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double-blind, randomized, placebo-controlled study.

OBJECTIVES: VSL#3 is a high-potency probiotic mixture that has been used successfully in the treatment of pouchitis. The primary end point of the study was to assess the effects of supplementation with VSL#3 in patients affected by relapsing ulcerative colitis (UC) who are already under treatment with 5-aminosalicylic acid (ASA) and/or immunosuppressants at stable doses. METHODS: A total of 144 consecutive patients were randomly treated for 8 weeks with VSL#3 at a dose of 3,600 billion CFU/day (71 patients) or with placebo (73 patients). RESULTS: In all, 65 patients in the VSL#3 group and 66 patients in the placebo group completed the study. The decrease in ulcerative colitis disease activity index (UCDAI) scores of 50% or more was higher in the VSL#3 group than in the placebo group (63.1 vs. 40.8; per protocol (PP) P=0.010, confidence interval (CI)95(%) 0.51-0.74; intention to treat (ITT) P=0.031, CI95(%) 0.47-0.69). Significant results with VSL#3 were recorded in an improvement of three points or more in the UCDAI score (60.5% vs. 41.4%; PP P=0.017, CI95(%) 0.51-0.74; ITT P=0.046, CI95(%) 0.47-0.69) and in rectal bleeding (PP P=0.014, CI95(%) 0.46-0.70; ITT P=0.036, CI95(%) 0.41-0.65), whereas stool frequency (PP P=0.202, CI95(%) 0.39-0.63; ITT P=0.229, CI95(%) 0.35-0.57), physician's rate of disease activity (PP P=0.088, CI95(%) 0.34-0.58; ITT P=0.168, CI95(%) 0.31-0.53), and endoscopic scores (PP P=0.086, CI95(%) 0.74-0.92; ITT P=0.366, CI95(%) 0.66-0.86) did not show statistical differences. Remission was higher in the VSL#3 group than in the placebo group (47.7% vs. 32.4%; PP P=0.069, CI95(%) 0.36-0.60; ITT P=0.132, CI95(%) 0.33-0.56). Eight patients on VSL#3 (11.2%) and nine patients on placebo (12.3%) reported mild side effects. CONCLUSIONS: VSL#3 supplementation is safe and able to reduce UCDAI scores in patients affected by relapsing mild-to-moderate UC who are under treatment with 5-ASA and/or immunosuppressants. Moreover, VSL#3 improves rectal bleeding and seems to reinduce remission in relapsing UC patients after 8 weeks of treatment, although these parameters do not reach statistical significance.

Short-term therapy with celecoxib and lansoprazole modulates Th1/ Th2 immune response in human gastric mucosa.

BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors and proton pump inhibitors may exert immune-mediated effects in human gastric mucosa. T-cell immune response plays a role in Helicobacter pylori-induced pathogenesis. This study evaluated effects of celecoxib and lansoprazole on T-helper (Th) 1 and Th2 immune response in human gastric mucosa. METHODS: Dyspeptic patients with or without osteoarticular pain were given one of the following 4-week therapies: celecoxib 200 mg, celecoxib 200 mg plus lansoprazole 30 mg, and lansoprazole 30 mg daily. Expression of COX-2, T-bet, and pSTAT6 and production of prostaglandin E2 (PGE2), interferon (IFN)-γ, and interleukin (IL)-4 were determined in gastric biopsies before and after therapy. Histology was evaluated. RESULTS: Cyclooxygenase-2 expression and PGE2 production was higher, and Th1 signaling pathway was predominant in H. pylori-infected vs. uninfected patients. T-bet expression and IFN-γ production increased, while STAT6 activation and IL-4 production decreased following therapy with celecoxib and celecoxib plus lansoprazole, respectively. Th1 and Th2 signaling pathways down-regulated after therapy with lansoprazole, and this was associated with an improvement of gastritis. Effect of therapy was not affected by H. pylori status. CONCLUSION: Celecoxib and lansoprazole modulate Th1/Th2 immune response in human gastric mucosa. The use of these drugs may interfere with long-term course of gastritis.

Barriers and Facilitators in Conducting Clinical Trials in Inflammatory Bowel Disease: A Monocentric Italian Survey.

BACKGROUND: Clinical therapeutic trials are a fundamental tool for identifying and testing new categories of drugs useful for ensuring clinical benefit in patients with Inflammatory Bowel Diseases (IBD). A number of difficulties may affect the recruitment process in large clinical trials. OBJECTIVES: In order to increase the involvement of patients within clinical trials in IBD therapy, it is necessary to identify which factors could facilitate or discourage participation. The aim of this study was to evaluate the factors influencing the participation in clinical trials in a consecutive series of patients with IBD from a single referral center from Southern Italy. METHODS: Consecutive patients with Crohn´s Disease (CD) and Ulcerative Colitis (UC) were recruited to complete a questionnaire dealing with their knowledge about clinical trials and attitudes towards participation. Patients also completed the Short Inflammatory Bowel Disease Questionnaire (S-IBDQ) to investigate their Quality of Life (QoL). Demographic and clinical data were recorded. RESULTS: Of the 145 consecutive patients invited to the survey, 132 completed the survey (91% response rate). Of them, 67% claimed their willingness to take part in a clinical therapeutic trial for IBD. Multivariate analysis showed a significant positive association between interest in clinical trials and previous experience (p = 0.014), high education (p < 0.001), poor QoL (p = 0.016), money retributions (p = 0.03) and informative materials (p = 0.02). On the other hand, a long-standing disease (p = 0.017), the possibility of receiving a placebo (p = 0.04) and the frequent colonoscopies required by the study protocol (p = 0.04) were significantly associated with the lack of interest in clinical trials. CONCLUSION: In a native local resident series of IBD patients, the majority of the patients were willing to participate in a clinical therapeutic trial. A long-standing disease, placebo and invasive procedures represented a barrier to enrollment while previous experience, high education, monetary compensation and adequate information could be facilitative. Knowing barriers and facilitators affecting participation in IBD clinical trials is of fundamental importance in order to increase the involvement of patients in research and explore new treatment opportunities.

The Reality of Patient-Reported Outcomes of Health-Related Quality of Life in an Italian Cohort of Patients with Inflammatory Bowel Disease: Results from a Cross-Sectional Study.

Inflammatory bowel disease (IBD) has a negative impact on patients' physical and psychological well-being, social performance, and working capacity, thereby worsening their health-related quality of life (HRQoL). Clinicians should take care of the patients' global health, including the psychological, social, and emotional spheres. We aimed to investigate the reality of patient-reported outcomes of HRQoL in a series of IBD patients. Consecutive Crohn´s disease (CD) and ulcerative colitis (UC) patients in clinical remission were recruited. The survey consisted of the Short Inflammatory Bowel Disease Questionnaire (S-IBDQ), the Hospital Anxiety and Depression Scale (HADS), the Brief Illness Perception Questionnaire (B-IPQ), and a questionnaire dealing with impact of IBD on patients' lives. Demographic and clinical characteristics were recorded. Of 202 participants (29% CD and 71% UC; 54% male; median age 48 years; mean disease duration 14 ± 11 years), 52% had poor HRQoL, 45% anxiety/depression, and 35% sleep disturbance and a high perception of disease (mean score 42.8 ± 14.3). In the multivariate analysis, a low HRQoL was rather associated with UC than CD (p = 0.037), IBD surgery (p = 0.010), disease duration (p = 0.01), sleep disturbance (p = 0.014), anxiety/depression (p = 0.042), and high illness perception (p = 0.006). IBD affected working performance and social activities in 62% and 74% of patients, respectively. Satisfaction regarding quality of care, biologics, and surgery approach were claimed in 73%, 69%, and 76% of patients, respectively. Although 84% of patients trusted their gastroenterologist, only 66% of them discussed IBD impact on HRQoL during visit. In a series of IBD patients in remission, the low HRQoL was significantly associated with surgery, disease duration, sleep disturbance, anxiety/depression, and high illness perception. Even though patients were satisfied with the quality of their care, it appears that clinicians should pay more attention to patients' emotional status.

Co-culture of human gastric endoscopic biopsies with Helicobacter pylori: a simple method for studying early phases of bacteria-host interaction.

Gastric biopsies obtained through endoscopy from patients uninfected by Helicobacter pylori were co-cultured with an H. pylori strain. According to tissue and H. pylori viability, interleukin 8 was increased in biopsy homogenate and supernatant after 12-36h culture. This simple method is suitable to investigate early phases of bacteria-host interaction.

Downregulation of Interleukin- (IL-) 17 through Enhanced Indoleamine 2,3-Dioxygenase (IDO) Induction by Curcumin: A Potential Mechanism of Tolerance towards Helicobacter pylori.

The anti-inflammatory and antimicrobial properties of curcumin suggest its use as an anti-Helicobacter pylori (H. pylori) agent, but mechanisms underlying its helpful activity are still not clear. Indoleamine 2,3-dioxygenase (IDO) promotes the effector T cell apoptosis by catalyzing the rate-limiting first step in tryptophan catabolism, and its high expression in H. pylori-infected human gastric mucosa attenuates Th1 and Th17 immune response. The aim of this study was to investigate the role of curcumin in modulating the expression of IL-17 and IDO in H. pylori-infected human gastric mucosa. In an organ culture chamber, gastric biopsies from 35 patients were treated with and without 200 µM curcumin. In H. pylori-infected patients (n = 21), IL-17 was significantly lower, both in gastric biopsies (p = 0.0003) and culture supernatant (p = 0.0001) while IDO significantly increased (p < 0.00001) in curcumin-treated sample compared with untreated samples. In a subgroup of H. pylori-infected patients (n = 15), samples treated with curcumin in addition to IDO inhibitor 1-methyl-L-tryptophan (1-MT) showed a higher expression of IL-17 compared with untreated samples and curcumin-treated alone (p < 0.00001). Curcumin downregulates IL-17 production through the induction of IDO in H. pylori-infected human gastric mucosa, suggesting its role in dampening H. pylori-induced immune-mediated inflammatory changes.

Potential role of nutraceutical compounds in inflammatory bowel disease.

Conventional therapies for inflammatory bowel diseases (IBD) involve combinations of pharmacologic agents such as aminosalicylates, azathioprine, and corticosteroids. Recently, the therapeutic scenario has been heavily increased by the introduction of agents including monoclonal antibodies targeted to specific proinflammatory cytokines, to adhesion molecules, and the induction of anti-inflammatory cytokines and T-cell activation. However, the use of these drugs is accompanied by a certain number of side effects, with some of them being quite severe, rising concerns about the safety profile. Furthermore, the cost of these emerging therapeutic strategies is significant , considering the increasing incidence and the chronic trend of IBD. Nutraceuticals is a broad term used to describe any product derived from food sources claiming extra health benefits beyond the intrinsic nutritional value found in foods. The beneficial effects of nutraceutical compounds in human health have been emerging in the last decades. Although few clinical trials have been performed in IBD patients, nutraceuticals, such as herbal products or vitamins, are generally accepted as safer alternative/supplementation to conventional therapy. In vitro and IBD-animal models studies have shown their involvement in several biological processes, including antioxidant defenses, cell proliferation, gene expression, which could account for a role in the maintenance of the mucosal barrier integrity, the control of the inflammatory pathways and the modulation of the immune response. These data suggest a wide spectrum of positive effects exerted by nutraceuticals, with a high potential for a therapeutic use in humans. In the present review, the beneficial effects of the most investigated nutraceutical compounds in the setting of human IBD are discussed.

Normal Bone Mineral Density Associates with Duodenal Mucosa Healing in Adult Patients with Celiac Disease on a Gluten-Free Diet.

Impairment of bone mineral density (BMD) is frequent in celiac disease (CD) patients on a gluten-free diet (GFD). The normalization of intestinal mucosa is still difficult to predict. We aim to investigate the relationship between BMD and duodenal mucosa healing (DMH) in CD patients on a GFD. Sixty-four consecutive CD patients on a GFD were recruited. After a median period of a 6-year GFD (range 2-33 years), patients underwent repeat duodenal biopsy and dual-energy X-ray absorptiometry (DXA) scan. Twenty-four patients (38%) displayed normal and 40 (62%) low BMD, 47 (73%) DMH, and 17 (27%) duodenal mucosa lesions. All patients but one with normal BMD (23 of 24, 96%) showed DMH, while, among those with low BMD, 24 (60%) did and 16 (40%) did not. At multivariate analysis, being older (odds ratio (OR) 1.1, 95% confidence interval (CI) 1.03-1.18) and having diagnosis at an older age (OR 1.09, 95% CI 1.03-1.16) were associated with low BMD; in turn, having normal BMD was the only variable independently associated with DMH (OR 17.5, 95% CI 1.6-192). In older CD patients and with late onset disease, BMD recovery is not guaranteed, despite a GFD. A normal DXA scan identified CD patients with DMH; thus, it is a potential tool in planning endoscopic resampling.

Oleuropein Decreases Cyclooxygenase-2 and Interleukin-17 Expression and Attenuates Inflammatory Damage in Colonic Samples from Ulcerative Colitis Patients.

Oleuropein (OLE) is the major phenolic secoiridoid of olive tree leaves, and its antioxidant and anti-inflammatory activities have been demonstrated in in vitro and in vivo animal models. The aim of this study was to investigate the activity of OLE in the colonic mucosa from patients with ulcerative colitis (UC). Biopsies obtained during colonoscopy from 14 patients with active UC were immediately placed in an organ culture chamber and challenged with lipopolysaccharide from Escherichia coli (EC-LPS) at 1 µg/mL in the presence or absence of 3 mM OLE. The expression of cyclooxygenase (COX)-2 and interleukin (IL)-17 was assessed in total protein extracts from treated colonic biopsies by Western blotting. Levels of IL-17 were also measured in culture supernatant by ELISA. A microscopic evaluation of the cultured biopsies was performed by conventional histology and immunohistochemistry. The expression of COX-2 and IL-17 were significantly lower in samples treated with OLE + EC-LPS compared with those treated with EC-LPS alone (0.80 ± 0.15 arbitrary units (a.u.) vs. 1.06 ± 0.19 a.u., p = 0.003, and 0.71 ± 0.08 a.u. vs. 1.26 ± 0.42 a.u., p = 0.03, respectively) as were the levels of IL-17 in culture supernatants of OLE + EC-LPS treated colonic samples (21.16 ± 8.64 pg/mL vs. 40.67 ± 9.24 pg/mL, p = 0.01). Histologically, OLE-treated colonic samples showed an amelioration of inflammatory damage with reduced infiltration of CD3, CD4, and CD20 cells, while CD68 numbers increased. The anti-inflammatory activity of OLE was demonstrated in colonic biopsies from UC patients. These new data support a potential role of OLE in the treatment of UC.

Giardia lamblia infection in patients with irritable bowel syndrome and dyspepsia: a prospective study.

AIM: To evaluate the prevalence of Giardia lamblia (G. lamblia) infection in patients with irritable bowel syndrome (IBS) and dyspepsia and to establish which is the most accurate test to diagnose the infection in this setting. METHODS: One hundred and thirty-seven patients who consecutively attended the Outpatient Gastroenterology Clinic for the first time between January 2002 and December 2003 due to symptoms of IBS and/or dyspepsia were recruited. All patients underwent clinical evaluation, first-step haematology and chemistry tests, serologic assays for celiac disease, lactose-H(2) breath test, abdominal ultrasonography, and esophagogastroduodenoscopy. Helicobacter pylori status was evaluated. In patients with symptoms of IBS older than 45 years, colonoscopy was also performed. In all patients, duodenal biopsies and stool samples were examined for trophozoites and cysts of G. lamblia by several methods. RESULTS: G. lamblia was identified in 9 patients. The following diagnoses were also made: IBS (100/137, 73%), functional dyspepsia (62/137, 45%), organic dyspepsia (33/137, 24%), and lactose intolerance (75/137, 55%). A significant association was found between giardiasis and H pylori infection (c2=6.632, OR=12.4, CI=1.5-68.1). There were no symptoms that reliably allowed the recognition of giardiasis. Direct search of the parasite in duodenal biopsy and stool sample examinations gave concordant results in all cases while histological examination of duodenal biopsies displayed a low sensitivity (e.g., 22.2%). CONCLUSION: In this consecutive series, diagnosis of G. lamblia infection accounted for 6.5% of patients with IBS and dyspepsia. Duodenal biopsies for diagnosis of giardiasis may be unnecessary if stool sample examination is performed.

Helicobacter pylori and T Helper Cells: Mechanisms of Immune Escape and Tolerance.

Helicobacter pylori colonizes the gastric mucosa of at least half of the human population, causing a worldwide infection that appears in early childhood and if not treated, it can persist for life. The presence of symptoms and their severity depend on bacterial components, host susceptibility, and environmental factors, which allow H. pylori to switch between commensalism and pathogenicity. H. pylori-driven interactions with the host immune system underlie the persistence of the infection in humans, since the bacterium is able to interfere with the activity of innate and adaptive immune cells, reducing the inflammatory response in its favour. Gastritis due to H. pylori results from a complex interaction between several T cell subsets. In particular, H. pylori is known to induce a T helper (Th)1/Th17 cell response-driven gastritis, whose impaired modulation caused by the bacterium is thought to sustain the ongoing inflammatory condition and the unsuccessful clearing of the infection. In this review we discuss the current findings underlying the mechanisms implemented by H. pylori to alter the T helper lymphocyte proliferation, thus facilitating the development of chronic infections and allowing the survival of the bacterium in the human host.

Bone mineralization in celiac disease.

Evidence indicates a well-established relationship between low bone mineral density (BMD) and celiac disease (CD), but data on the pathogenesis of bone derangement in this setting are still inconclusive. In patients with symptomatic CD, low BMD appears to be directly related to the intestinal malabsorption. Adherence to a strict gluten-free diet (GFD) will reverse the histological changes in the intestine and also the biochemical evidence of calcium malabsorption, resulting in rapid increase of BMD. Nevertheless, GFD improves BMD but does not normalize it in all patients, even after the recovery of intestinal mucosa. Other mechanisms of bone injury than calcium and vitamin D malabsorption are thought to be involved, such as proinflammatory cytokines, parathyroid function abnormalities, and misbalanced bone remodeling factors, most of all represented by the receptor activator of nuclear factor B/receptor activator of nuclear factor B-ligand/osteoprotegerin system. By means of dual-energy X-ray absorptiometry (DXA), it is now rapid and easy to obtain semiquantitative values of BMD. However, the question is still open about who and when submit to DXA evaluation in CD, in order to estimate risk of fractures. Furthermore, additional information on the role of nutritional supplements and alternative therapies is needed.

No evidence of circulating autoantibodies against osteoprotegerin in patients with celiac disease.

AIM: To investigate risk factors for low bone mineral density (BMD) in celiac disease (CD) patients, focusing on circulating autoantibodies against osteoprotegerin (OPG). METHODS: Seventy asymptomatic CD adult patients on gluten-free diet (GFD) and harbouring persistent negative CD-related serology were recruited. Conventional risk factors for osteoporosis (e.g., age, sex, menopausal status, history of fractures, smoke, and body mass index) were checked and BMD was assessed by dual energy X ray absorptiometry. Serum calcium and parathyroid hormone (PTH) levels were evaluated. Thirty-eight patients underwent repeat duodenal biopsy. Serum samples from a selected sub-group of 30 patients, who were also typed for human leukocyte antigen (HLA) DQ2 and DQ8 haplotype, were incubated with homodimeric recombinant human OPG and tested by western blotting with an anti-OPG antibody after immunoprecipitation. RESULTS: Despite persistent negative CD-related serology and strict adherence to GFD, 49 out of the 70 (74%) patients displayed low BMD. Among these patients, 13 (24%) showed osteoporosis and 36 (76%) osteopenia. With the exception of age, conventional risk factors for osteoporosis did not differ between patients with normal and low BMD. Circulating serum calcium and PTH levels were normal in all patients. Duodenal mucosa healing was found in 31 (82%) out of 38 patients who underwent repeat duodenal biopsy with 20 (64%) still displaying low BMD. The remaining 7 patients had an incomplete normalization of duodenal mucosa with 6 (84%) showing low BMD. No evidence of circulating antibodies against OPG was found in the serum of 30 celiac patients who were tested for, independent of BMD, duodenal histology, and HLA status. CONCLUSION: If any, the role of circulating autoantibodies against OPG in the pathogenesis of bone derangement in patients with CD is not a major one.