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

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)\u2089\u2085(%) 0.51-0.74; intention to treat (ITT) P=0.031, CI\u2089\u2085(%) 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, CI\u2089\u2085(%) 0.51-0.74; ITT P=0.046, CI\u2089\u2085(%) 0.47-0.69) and in rectal bleeding (PP P=0.014, CI\u2089\u2085(%) 0.46-0.70; ITT P=0.036, CI\u2089\u2085(%) 0.41-0.65), whereas stool frequency (PP P=0.202, CI\u2089\u2085(%) 0.39-0.63; ITT P=0.229, CI\u2089\u2085(%) 0.35-0.57), physician's rate of disease activity (PP P=0.088, CI\u2089\u2085(%) 0.34-0.58; ITT P=0.168, CI\u2089\u2085(%) 0.31-0.53), and endoscopic scores (PP P=0.086, CI\u2089\u2085(%) 0.74-0.92; ITT P=0.366, CI\u2089\u2085(%) 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, CI\u2089\u2085(%) 0.36-0.60; ITT P=0.132, CI\u2089\u2085(%) 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

Long-term, Real-life, Observational Study in Treating Outpatient Ulcerative Colitis with Golimumab

Background and Aims: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. Methods: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. Results: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. Conclusions: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good

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

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

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

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)

Refractory Ulcerative Colitis Complicated by Cytomegalovirus Infection Successfully Treated With Valganciclovir

Cytomegalovirus (CMV) infection is widespread in the general population. In patients with severe and/or steroid-refractory ulcerative colitis (UC), local reactivation of CMV can be detected in actively inflamed colonic tissue in approximately 30% of cases. However, the role of CMV in patients with UC is not clearly understood. There is evidence to show a possible role in exacerbating a colitis flare, whereas other studies describe CMV as an innocent bystander. We report the case of a patient with severe UC complicated by CMV infection who did not respond to conventional therapy. A complete diagnostic panel for CMV diagnosis, including tissue polymerase chain reaction and immunohistochemistry, was carried out. Three-week therapy with oral valganciclovir resulted in dramatic clinical and endoscopic improvement. Timing of diagnosis and treatment of CMV infection complicating UC is crucial in order to recognize the organ-disease and plan appropriate treatment

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